Objective:To investigate the effects of melatonin on renal inflammation,oxidative stress,apoptosis,as well as DNA and tissue damage in acrylamide-induced nephrotoxicity in rats.Methods:Fifty male rats were randomly di...Objective:To investigate the effects of melatonin on renal inflammation,oxidative stress,apoptosis,as well as DNA and tissue damage in acrylamide-induced nephrotoxicity in rats.Methods:Fifty male rats were randomly divided into five groups.The control group received distilled water by gastric lavage for 11days and the acrylamide group was administered acrylamide(50 mg/kg,i.g.)for 11 days.The MEL10+ACR and MEL20+ACR groups received intraperitoneal melatonin 10 and 20 mg/kg,respectively,for 11 days,and acrylamide(50 mg/kg,i.g.)was administered 1h after melatonin injection.The MEL20 group was injected with melatonin(20 mg/kg)for 11 days.Kidney function tests were performed and biochemical and inflammatory parameters were determined.In addition,histopathological,immunohistochemical,and immunofluorescence examinations were carried out.Results:Melatonin significantly abated acrylamide-induced rise in serum urea and creatinine levels.Acrylamide caused oxidative stress,inflammation,apoptosis,as well as DNA and tissue damage in the kidneys.Melatonin treatment alleviated acrylamide-induced renal damage by exhibiting antioxidant,anti-inflammatory,and antiapoptotic effects.Moreover,melatonin significantly ameliorated acrylamide-caused histopathological changes in kidney tissue.Conclusions:Melatonin attenuates acrylamide-induced renal oxidative stress,inflammation,apoptosis,and DNA damage in rats.展开更多
Emodin is an effective component of rhubarb with positive pharmacological effects on human health.However,it is also toxic to different cells or tissues to varying degrees.The effects of emodin on glomerular endotheli...Emodin is an effective component of rhubarb with positive pharmacological effects on human health.However,it is also toxic to different cells or tissues to varying degrees.The effects of emodin on glomerular endothelial cells(GECs)remain to be tested,and the documented works were always performed in vitro and hardly reflect the real physiological situation.To study the effects of emodin on GECs in a biomimetic environment,we utilized a microfluidic chip to assess the physiological reaction of human renal glomerular endothelial cells to various concentrations of emodin in this work.The results showed that emodin caused cytotoxicity,impaired glomerular filtration barrier integrity to macromolecules,and increased barrier permeability in a dose-dependent manner.With the increase in emodin concentration,the concentration of the pro-inflammatory cytokine tumor necrosis factor-α,interleukin(IL)-6,transforming growth factor-β1,and monocyte chemoattractant protein(MCP-1)increased while the production of inflammatory cytokine IL-6 first increased and then decreased with the increase in emodin concentration.Our findings shed new light on emodin-induced nephrotoxicity and provide insights for the application of microfluidic chip devices to reveal drug-cell interactions.展开更多
This paper analyzes the relationship between toxicity and safety of traditional Chinese medicine(TCM)based on the cases of current nephrotoxicity and hepatotoxicity,and summarizes the literature on hepatotoxicity and ...This paper analyzes the relationship between toxicity and safety of traditional Chinese medicine(TCM)based on the cases of current nephrotoxicity and hepatotoxicity,and summarizes the literature on hepatotoxicity and nephrotoxicity.It is found that the main reasons for the toxic reaction of TCM are own factors of drugs,irregular administration of medicine and individual difference.However,as long as the"quality"and"quantity"of TCM are guaranteed,the toxicity of TCM can be controlled within the safety range.展开更多
Licorice,one of the most widely used medicinal herbs in East Asia,has effects such as anti-inflammation,antioxidant,and detoxifying.This study aimed to evaluate the protective effect of licorice on brucine-induced nep...Licorice,one of the most widely used medicinal herbs in East Asia,has effects such as anti-inflammation,antioxidant,and detoxifying.This study aimed to evaluate the protective effect of licorice on brucine-induced nephrotoxicity.Sprague Dawley rats were administered with brucine intraperitoneally for 7 consecutive days with or without treatment with licorice.The content of blood urea nitrogen and creatinine in serum,the activities of superoxide dismutase and content of glutathione,malonaldehyde in kidney tissue were detected.Hematoxylin-eosin staining was employed to observe the histopathological changes of kidney.The expression and phosphorylation levels of protein were evaluated by Western blotting and immunohistochemical analysis.The results illustrated that treatment with licorice extracts(LE)significantly protected against the brucineinduced nephrotoxicity by reducing the content of blood urea nitrogen and serum creatinine,attenuating pathologic damage.The unbalance of oxidative stress was repaired by LE via increasing the level of glutathione,promoting the activities of superoxide dismutase and decreasing the content of malonaldehyde.In addition,LE overturned the influence of brucine on apoptosis-related protein and signal transducer and activator of transcription-3(STAT3)activation.Taken together,these data demonstrate that licorice may attenuate brucine-induced nephrotoxicity via inactivation of oxidative stress and mitochondrial-mediated apoptosis pathway.More importantly,the renoprotective effects may be mediated,at least partly,by preventing the activation of STAT3 protein.展开更多
Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which wa...Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which was a mean of increasing their therapeutic index,reducing their toxicity and altering drug biodistribution.One of the challenges for preparing VANH-Lips is their low encapsulation efficiency(EE).In the present study,we aim to improve the liposomal formulation of VANH for higher EE,longer systemic circulation,reduced nephrotoxicity and enhanced antimicrobial activities.Vancomycin hydrochloride-loaded liposomes(VANH-Lips)were formulated by the method of modified reverse phase evaporation.Based on the optimization of formulation with orthogonal experimental design,the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78±2.56%and 188.4±2.77 nm.In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation.After intravenous injection to mice,the mean residence time(MRT)of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution(VANH-Sol)group.Furthermore,the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection.In conclusion,VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.展开更多
Anticancer drug nephrotoxicity is an important and increasing adverse drug event that limits the efficacy of cancer treatment.The kidney is an important elimination pathway for many antineoplastic drugs and their meta...Anticancer drug nephrotoxicity is an important and increasing adverse drug event that limits the efficacy of cancer treatment.The kidney is an important elimination pathway for many antineoplastic drugs and their metabolites,which occurs by glomerular filtration and tubular secretion.Chemotherapeutic agents,both conventional cytotoxic agents and molecularly targeted agents,can affect any segment of the nephron including its microvasculature,leading to many clinical manifestations such as proteinuria,hypertension,electrolyte disturbances,glomerulopathy,acute and chronic interstitial nephritis,acute kidney injury and at times chronic kidney disease.The clinician should be alert to recognize several factors that may maximize renal dysfunction and contribute to the increased incidence of nephrotoxicity associated with these drugs,such as intravascular volume depletion,the associated use of nonchemotherapeutic nephrotoxic drugs(analgesics,antibiotics,proton pump inhibitors,and bonetargeted therapies),radiographic ionic contrast media or radiation therapy,urinary tract obstruction,and intrinsic renal disease.Identification of patients at higher risk for nephrotoxicity may allow the prevention or at least reduction in the development and severity of this adverse effect.Therefore,the aim of this brief review is to provide currently available evidences on oncologic drug-related nephrotoxicity.展开更多
Objective:To evaluate nephroprotective potential of Solarium xanthocarpum(S.xanthocarpum) fruit extract(SXE) against gentamicin(GM) induced nephrotoxicity) and renal dysfunction. Methods:Twenty-four Wistar rats were d...Objective:To evaluate nephroprotective potential of Solarium xanthocarpum(S.xanthocarpum) fruit extract(SXE) against gentamicin(GM) induced nephrotoxicity) and renal dysfunction. Methods:Twenty-four Wistar rats were divided into four groups(n=6).Control rats that received normal saline(i.p.) and 0.5%carboxymethyl cellulose(p.o.) per day lor 8 d.Nephrotoxicity was induced in rats by intraperitoneal administration of GM(100 mg/kg/d for 8 d) and were treated with SXE(200 and 400 mg/kg/d(p.o.) for 8 d).Plasma and urine urea and creatinine,kidney weight,urine output,blood urea nitrogen,renal enzymatic and non-enzymatic antioxidants and lipid peroxidation was evaluated along with histopathological investigation in various experimental groupsof rats.Results:It was observed that the GM treatment induced significant elevation(P【0.001) in plasma and urine urea,creatinine,kidney weight,blood urea nitrogen, renal lipid peroxidation along with significant decrement(P【0.001) in urine output,renal enzymatic and non-enzymatic antioxidants.SXE 200 and 400 mg/kg treatment to GM treated rats recorded significant decrement(up to P【0.001) in plasma and mine urea and creatinine, renal lipid peroxidation along with significanl increment(up to P【0.001) in renal enzymatic and non-enzvmatic antioxidants.Histological obsenatioiis of kidney tissues too correlated with the biochemical obsenatioiis.Conclusions:These finding powerfully supports that S,xanthocarpum fruit extract acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM both in the biochemical and histopathological parameters and thus validates its elhnomedicinal use.展开更多
Objective:To explore the possible effects of naringin on acrylamide-induced nephrotoxicity in rats.Methods:Sprague-Dawley rats weighing 200-250 g were randomly divided into five groups.The control group was given intr...Objective:To explore the possible effects of naringin on acrylamide-induced nephrotoxicity in rats.Methods:Sprague-Dawley rats weighing 200-250 g were randomly divided into five groups.The control group was given intragastric(i.g.)saline(1 mL)for 10 d.The acrylamide group was given i.g.acrylamide in saline(38.27 mg/kg titrated to 1 mL)for 10 d.The treatment groups were administered with naringin in saline(50 and 100 mg/kg,respectively)for 10 d and given i.g.acrylamide(38.27 mg/kg)1 h after naringin injection.The naringin group was given i.g.naringin(100 mg/kg)alone for 10 d.On day 11,intracardiac blood samples were obtained from the rats when they were under anesthesia,after which they were euthanized.Urea and creatinine concentrations of blood serum samples were analyzed with an autoanalyzer.Enzyme-linked immunosorbent assay was used to quantify malondialdehyde,superoxide dismutase,glutathione,glutathione peroxidase,catalase,tumor necrosis factor-α,nuclear factor-κB,interleukin(IL)-33,IL-6,IL-1β,cyclooxygenase-2,kidney injury molecule-1,mitogen-activated protein kinase-1,and caspase-3 in kidney tissues.Renal tissues were also evaluated by histopathological and immunohistochemical examinations for 8-OHdG and Bcl-2.Results:Naringin attenuated acrylamide-induced nephrotoxicity by significantly decreasing serum urea and creatinine levels.Naringin increased superoxide dismutase,glutathione,glutathione peroxidase,and catalase activities and decreased malondialdehyde levels in kidney tissues.In addition,naringin reduced the levels of inflammatory and apoptotic parameters in kidney tissues.The histopathological assay showed that acrylamide caused histopathological changes and DNA damage,which were ameliorated by naringin.Conclusions:Naringin attenuated inflammation,apoptosis,oxidative stress,and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats.展开更多
This study aimed to assess the preventive effects of thyme oil and thymol on doxorubicin(DOX)-induced renotoxicity,cardiotoxicity,and oxidative stress in Wistar rats.Thyme oil was subjected to GC-MS analysis,which ind...This study aimed to assess the preventive effects of thyme oil and thymol on doxorubicin(DOX)-induced renotoxicity,cardiotoxicity,and oxidative stress in Wistar rats.Thyme oil was subjected to GC-MS analysis,which indicated that thymol was the major constituent representing 33.896%.Rats intraperitoneally injected with DOX at a dose of 2 mg/kg b.w./one per week for 7 weeks were co-treated with thyme oil and its major constituent,thymol,at doses 250 and 100 mg/kg b.w./every other day,respectively,by oral gavage for the same period.Thyme oil and thymol markedly ameliorated the raised levels of serum urea,uric acid,and creatinine in DOX-administered rats.They also reduced the elevated activities of serum CK-MB and LDH.Thyme oil was more effective than thymol in decreasing the elevated serum creatinine level and serum CK-MB activity in DOX-administered rats,thereby reflecting its more potent effect on kidney and heart functions.Lipid peroxidation significantly decreased while GSH level and GST and GPx activities significantly increased in kidney and heart of DOX-administered rats treated with thyme oil and thymol.The DOX-induced perturbed kidney histological changes including congestion of glomerulus tuft,inflammatory cells infiltration,protein cast in lumina of the renal tubule,and thickening of the parietal layer of Bowman’s capsule were remarkably ameliorated as a result of treatment with thyme oil and thymol;thyme oil was more effective.In addition,DOX-induced deleterious heart histological alterations,including intramuscular infiltration of inflammatory cells,focal necrosis of cardiac myocytes,and edema,were remarkably reduced by treatment with thyme oil and thymol.Thus,it can be concluded that DOX could induce marked toxicity in kidney and heart,and the treatment with thyme oil or thymol produced potential improvement of kidney and heart function and histological integrity via repression of oxidative stress and enhancement of antioxidant defense mechanisms.展开更多
Objective: To evaluate the nephroprotective effect of defatted mehtanolic extract and aqueous extract of Murraya koenigii against Cyclophosphamide drug. Methods: Nephrotoxicity was induced by Cyclophosphamide in 7 d a...Objective: To evaluate the nephroprotective effect of defatted mehtanolic extract and aqueous extract of Murraya koenigii against Cyclophosphamide drug. Methods: Nephrotoxicity was induced by Cyclophosphamide in 7 d at 150 mg/kg body weight through intraperitoneal route in rat model. Nephroprotective activity of Murraya koenigii(M. koenigii) extract(100 mg/kg and 200 mg/kg in intraperitoneal route) was measured, including nephrological source, oxidative stress parameters like superoxide dismutase, glutathione, the lipid peroxide and in vivo assay like blood urea nitrogen, creatinine were determined and analyzed by One way analysis of variance followed by Tukey's test. Results: The study result showed that important phytochemicals such as carbohydrates, flavonoids, tannin, alkaloids, glycosides, protein and steroids were found to be present in the extract of M. koenigii. The renal function markers like blood urea nitrogen and ceatinine level were found to be decreased significantly by M. koenigii extract treatment. A significant difference was found to be at P<0.01. Conclusions: The present study reveals the protective role of M. koenigii extract against Cyclophosphamide induced nephrotoxicity.展开更多
Cyclosporine (CsA) has revolutionized transplant medicine and is currently one of the most important immunosuppressive agents for a wide range of organ transplantations and of autoimmune and inflammatory diseases, suc...Cyclosporine (CsA) has revolutionized transplant medicine and is currently one of the most important immunosuppressive agents for a wide range of organ transplantations and of autoimmune and inflammatory diseases, such as rheumatoid arthritis, uveitis, psoriasis, and atopic dermatitis. Renal impairment represents the main limitation to CsA long-term continuous therapy. However, it has been shown that nephrotoxicity is associated with longer treatment duration, larger cumulative doses and higher daily dose of CsA. With low dose regimens (<5 mg/kg/day), stable serum creatinine levels have been observed up to 15-20 years after kidney transplantation. Intermittent therapy may offer a good therapeutic strategy to limit long-term renal dysfunction, given the fact that renal structural changes are dose- and time-dependent. The best predictor of permanent renal damage is a persistent increase in serum creatinine level one month after treatment withdrawal. In patients with autoimmune diseases, the percentage increase in serum creatinine above baseline value during CsA therapy has been shown to predict CsA-induced nephropathy. Before CsA therapy initiation, patients should undergo a thorough baseline evaluation including laboratory assessments, in particular electrolytes, serum creatinine, and urea levels. Furthermore, patients should be evaluated for factors that might increase the risk of nephrotoxicity, such as obesity, older age, hypertension, concomitant use of nephrotoxic drugs, and pre-existing renal conditions. In the present paper, CsA-induced nephropathy will be reviewed in terms of pathophysiology, pathologic and clinical findings, and strategies for prevention and management.展开更多
Objective:To investigate the antioxidant ef ect of an orally administered ethanol extract of nettle(Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin...Objective:To investigate the antioxidant ef ect of an orally administered ethanol extract of nettle(Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin-induced nephrotoxicity in male rabbits. Methods: Twenty rabbits were divided into 4 equal groups:(G1) control group,(G2) gentamicin treated group(100 mg/kg),(G3) nettle treated group(100 mg/kg),(G4) combination treated group with both gentamicin(100 mg/kg) and nettle(100 mg/kg) for 10 days. The antioxidant properties of nettle were evaluated using dif erent antioxidant tests, such as determination of glutathione and malondialdehyde levels and total phenolic content analysis. Results: Biochemical and histopathological study revealed that gentamicin caused nephrotoxicity observed clearly in the histopathological section of the kidney in the gentamicin treated group. Serum creatinine and blood urea nitrogen were biochemical indicators for nephrotoxicity which increased signii cantly in gentamicin treated group; other groups have no signii cant change in these two parameters. Nettle extract protected the rabbits from alteration in the level of blood urea nitrogen and serum creatinine when given after inducing of gentamicin nephrotoxicity. The nettle treated group showed a great ef ect as an antioxidant factor by increasing the glutathione level and reducing malondialdehyde level. No signii cant changes in biochemical parameters and no renal histopathological changes observed in the groups treated with nettle extract, which meant nettle had powerful antioxidant activity. Conclusions: Therefore, it can be assumed that the nephroprotective ef ect shown by nettle in gentamicin-induced nephrotoxicity can reserve intracellular levels of biological pathways and supportively enhance excretion of toxic levels of gentamicin.展开更多
Objective:To highlight the nephroprotective activity of ethyl acetate extract of dried flowers of Tecomu stans for its protective effects on genlamicin-induced nephrotoxicity in albino rats. Methods:For studying acute...Objective:To highlight the nephroprotective activity of ethyl acetate extract of dried flowers of Tecomu stans for its protective effects on genlamicin-induced nephrotoxicity in albino rats. Methods:For studying acute toxicity study,single oral dose of 5（KM） mg ethyl acetate floral extract/kg hodv weight was administered to albino rats（five females,five males）.Nephrotoxicity was induced in albino rats by intraperitoneal administration of gentamicin 80 mg/kg/day for eight days.Effect of concurrent administration of ethyl acetate floral extract of Tecoma stans at a dose of 100.200 and 300 mg/kg/day given by oral mute was determined using serum creatinine,serum uric acid,blood urea nitrogen and serum urea as indicators of kidney damage.The study groups contained six rats in each group.As nephrotoxicity of gentamicin is known to involve induction of oxidative stress,in vitro antioxidant aclivity and free radical-scavenging activity of this extract was also evaluated.Results:For acute toxicity testing both female and male rats administered with the extract at a dose of 5 000 mg/kg.The results showed no toxicity in terms of general behavior change,mortality,or change in gross appearance of internal organs(LD<sub>50</sub>】5 000 mg/kg). It was observed that the ethyl acetate floral extract of Tecoma stans significantly protected rat kidneys from gentamicin-induced histopathological changes.Gentamicin-induced glomerular congestion,peritubular and blood vessel congestion,epithelial desquamation,accumulation ol inflamnialoiy cells and necrosis of the kidney cells were found to be reduced in the groups receiving the ethyl acetate floral extract of Tecoma starts along with gentamicin in a dose dependent manner.The floral extract also reduced the gentamicin-induced increase in serum creatinine,serum uric acid,blood urea nitrogen and serum urea levels（P】0.01）.Conclusions: The present study indicates a verv important role of reactive oxygen species（BOS） and the relation to renal dysfunction and point to the therapeutic potential of Tecoma stans in gentamicin induced nephrotoxicity.展开更多
Aim Ethnopharmacological relevance： Ribes diacanthum Pall. （Saxifragaceae） , a Mongolian folk me- dicinal plant, was used to treat urinary system diseases. The present work aims to investigate the protective effect...Aim Ethnopharmacological relevance： Ribes diacanthum Pall. （Saxifragaceae） , a Mongolian folk me- dicinal plant, was used to treat urinary system diseases. The present work aims to investigate the protective effects of Ribes diacanthum Pall （RDP） against cisplatin-induced nephrotoxicity. Methods The renal injury was mod- eled by intraperitoneal injection of cisplatin for 5 consecutive days （5 mg·kg^-1 ）. Nephroprotection of RDP was investigated by oral administration of RDP aqueous extract at a daily dose of 40 mg · kg^- 1 for 14 consecutive days, starting 7 days prior to cisplatin administration. Results We demonstrated that pretreatment with RDP aqueous ex- tract protected the mice from death induced by cisplatin administration. RDP treatment also significantly reduced blood urea nitrogen （BUN） and serum creatinine （Cr） levels observed in cisplatin-administrated mice. Histopatho- logical analysis demonstrated that RDP administration protected cisplatin-induced renal tubular cell apoptosis. Fur- ther western blotting analysis revealed that RDP significantly reversed cisplatin-increased expression levels of cleaved-Caspase-3, Bax and cisplatin-decreased expression level of Bcl-2 in renal tissue. Finally, RDP markedly enhanced enzyme activities of reduced superoxide dismutase （SOD）, Heine oxygenase 1 （HO-1） and catalase （CAT）, suppressed lipid peroxidation as well as reactive oxygen species （ROS） production. Conclusion We concluded that RDP displayed nephroprotective effects against cisplatin-induced renal tubular cell apoptosis, possi- bly associated with both enhanced antioxidase activity and suppressed ROS generation. Given the major nephrotox- icity of cisplatin cancer chemotherapy, RDP might be a potential candidate for neoadjuvant chemotherapy.展开更多
Objective: To investigate the effects of probiotic bacteria on cisplatin(CP)-induced nephrotoxicity. Methods: In the present study, 50 Sprague-Dawley rats were used and randomly divided into five groups including cont...Objective: To investigate the effects of probiotic bacteria on cisplatin(CP)-induced nephrotoxicity. Methods: In the present study, 50 Sprague-Dawley rats were used and randomly divided into five groups including control, CP, probiotic bacteria treatment groups with different doses(0.5 and 1 mL) and only probiotic bacteria group. After CP and probiotic administration on seven days, rats sacrificed under anesthesia on the eighth day. The serum urea, creatinine, and blood urea nitrogen levels were analyzed. In renal tissue, malondialdehyde levels, superoxide dismutase and glutathione activity, interleukin-8, interleukin-1β and tumor necrosis factor-alpha levels were determined and histopathological and immunohistochemical changes were also examined. Results: According to results, urea, creatinine and blood urea nitrogen levels as well as kidney weights increased in CP group. Also, CP induced inflammation, oxidative stress, DNA damage and apoptosis in kidney tissue and caused histopathological changes. Administration of the high dose of probiotic bacteria could prevent these changes and damages. Conclusions: This study reveals that probiotic bacteria has protective effects on CP-induced renal damage in rats.展开更多
Objective: To investigate nephroprotective potential of Meristotropis xanthioides(M.xanthioides) extract against ethanol-induced nephrotoxicity in Wistar rats, and also its total phenolics content, antioxidant and ant...Objective: To investigate nephroprotective potential of Meristotropis xanthioides(M.xanthioides) extract against ethanol-induced nephrotoxicity in Wistar rats, and also its total phenolics content, antioxidant and antibacterial activities.Methods: Total phenol and flavonoid amounts of the leaf and stem extracts were determined by Folin–Ciocalteu and aluminum chloride reagents, respectively.Antioxidant and antibacterial activities of the extracts were investigated by 2,2-diphenyl-1-picrylhydrazyl radical scavenging and disc diffusion methods, respectively.In addition,protective potential of the leaf extract against ethanol-induced nephrotoxicity was studied by histological and biochemical analyses.Results: Obtained results indicated high total phenol [(10.26 ± 0.46) mg GAE/g of dry extract] and flavonoid [(3.63 ± 0.62) mg QE/g of dry extract] amounts in the leaf extract.The leaf and stem extracts possessed stronger antioxidant activity [IC_(50):(0.119 ± 0.006)mg/mL and IC_(50):(0.133 ± 0.009 mg/mL)] than that of ascorbic acid [IC_(50):(0.142 ± 0.002)mg/mL].Also, the extracts showed good antibacterial activity against the most of bacteria taken in this research, especially Gram-positive ones.Histological examinations revealed tissue injury in the kidney of rats treated with ethanol.Results from biochemical assays showed reduction in total protein content and also in superoxide dismutase activity.In addition, remarkable increased levels(P < 0.05) of H_2O_2 and malondialdehyde were found in ethanol-treated rats in comparison to control group.However, these injuries were significantly improved in rats treated by M.xanthioides leaf extract.Conclusions: Results from present study demonstrates strong pharmaceutical potential of M.xanthioides extract to apply as a new drug supplement.展开更多
Tisplatin is one of the valuable icancer agents against several types of neoplasm. However, nephrotoxicity is the major adverse effect representing in cisplatin therapy. In this study, the animal tests detecting prote...Tisplatin is one of the valuable icancer agents against several types of neoplasm. However, nephrotoxicity is the major adverse effect representing in cisplatin therapy. In this study, the animal tests detecting protective effects of a natural compound, Decursin, on cisplatin-induced nephrotoxicity were examined by using in vivo model. Pretreatment Decursin 10, 20 and 40 mg · kg-1 at 48, 24 and 6 h, and administration of a single dose of Cisplatin 5.2 mg · kg-1. Nephrotoxicity was evaluated by serum BUN and creatinine examination. There was significant difference in body weights, serum BUN and creatinine levels of the normal group. Based on the new understanding of the protective mechanisms of cisplatin-induced nephrotocivity, new strategies can be developed to prevent renal injury or to enhance recovery after cisplatin treatment.展开更多
Side effects of cisplatin,especially dose-dependent nephrotoxicity,are major factors limiting its use in cancer.Boldine((S)-2,9-dihydroxy-1,10-dimethoxy-aporphine)is a natural alkaloid known for its strong antioxidant...Side effects of cisplatin,especially dose-dependent nephrotoxicity,are major factors limiting its use in cancer.Boldine((S)-2,9-dihydroxy-1,10-dimethoxy-aporphine)is a natural alkaloid known for its strong antioxidant activity present in leaves/bark of boldo tree(Peumus boldus Molina),a native tree in Chile.Here,we aimed to investigate the nephroprotective effect of boldine and its underlying mechanisms on cisplatin-induced rat renal injury.Thirty Wistar albino rats divided into 5 groups(Control,Cis,Bold.40,Cis+Bold.20,Cis+Bold.40 groups)were used.Rats received boldine(20 or 40 mg/kg/day),or vehicle(saline)intraperitoneal for 14 days and a single dose cisplatin(7 mg/kg,ip)was applied on the 10th day to induce nephrotoxicity.Rats and kidney tissue were weighed to determine kidney index.Blood urea nitrojen(BUN)and creatinine levels,the amount of thiobarbituric acid reactive substances(TBARS,an index of lipid peroxidation),superoxide dismutase(SOD),glutathione peroxidase(GPx)enzyme activities and tumor necrosis factor alpha(TNF-α)levels were measured and histopathologic examination was performed.Inducible nitric oxide synthase(iNOS)and caspase-3 expressions were detected immunohistochemically.Nephrotoxicity induced by cisplatin was apparent by elevated levels of BUN,creatinine,kidney index,TBARS and TNF-α,and decreased body weight,SOD and GPx enzyme levels.Pretreatment with boldine protected the renal function at both boldine doses by fixing the renal damage markers,oxidative stress,caspase-3 and iNOS expression.Histopathological findings supported biochemical findings.Taken together these findings indicate that boldine has promising protective effect against cisplatin nephrotoxicity by improving oxidative stress,inflammation,histopathological alterations and by alleviating caspase 3 expression.展开更多
BACKGROUND Polymyxin-induced nephrotoxicity is a major safety concern in clinical practice due to long-term adverse outcomes and high mortality.AIM To conducted a systematic review and meta-analysis of the prevalence ...BACKGROUND Polymyxin-induced nephrotoxicity is a major safety concern in clinical practice due to long-term adverse outcomes and high mortality.AIM To conducted a systematic review and meta-analysis of the prevalence and potential predictors of polymyxin-induced nephrotoxicity in adult intensive care unit(ICU)patients.METHODS PubMed,EMBASE,the Cochrane Library and Reference Citation Analysis database were searched for relevant studies from inception through May 30,2022.The pooled prevalence of polymyxin-induced nephrotoxicity and pooled risk ratios of associated factors were analysed using a random-effects or fixed-effects model by Stata SE ver.12.1.Additionally,subgroup analyses and meta-regression were conducted to assess heterogeneity.RESULTS A total of 89 studies involving 12234 critically ill adult patients were included in the meta-analysis.The overall pooled incidence of polymyxin-induced nephrotoxicity was 34.8%.The pooled prevalence of colistin-induced nephrotoxicity was not higher than that of polymyxin B(PMB)-induced nephrotoxicity.The subgroup analyses showed that nephrotoxicity was significantly associated with dosing interval,nephrotoxicity criteria,age,publication year,study quality and sample size,which were confirmed in the univariable meta-regression analysis.Nephrotoxicity was significantly increased when the total daily dose was divided into 2 doses but not 3 or 4 doses.Furthermore,older age,the presence of sepsis or septic shock,hypoalbuminemia,and concomitant vancomycin or vasopressor use were independent risk factors for polymyxin-induced nephrotoxicity,while an elevated baseline glomerular filtration rate was a protective factor against colistin-induced nephrotoxicity.CONCLUSION Our findings indicated that the incidence of polymyxin-induced nephrotoxicity among ICU patients was high.It emphasizes the importance of additional efforts to manage ICU patients receiving polymyxins to decrease the risk of adverse outcomes.展开更多
Piroxicam is commonly used as anti-inflammatory and pain relieving drug;however, its side effects include fluid retention, renal damage and heart failure. This study aimed at evaluating the nephroprotective role of di...Piroxicam is commonly used as anti-inflammatory and pain relieving drug;however, its side effects include fluid retention, renal damage and heart failure. This study aimed at evaluating the nephroprotective role of different doses of the tannin-rich extract of Chasmanthera dependens stem (TRECDS) on piroxicam-induced nephrotoxicity in adult male Wistar rats. Thirty-two adult rats were divided into four groups of eight rats per group and treated orally for ten days. Rats in group one received 0.5 ml normal saline (0.9% v/v) and served as normal control group. Rats in group two received 20 mg/kg body weight piroxicam alone. Rats in groups three and four received 20 mg/kg body weight of piroxicam with concomitant administration of 200 and 400 mg/kg body weight of TRECDS. At the expiration of the experiment, rats were sacrificed and the kidney was removed. Renal function was evaluated. The results showed that administration of piroxicam alone caused a significant elevation in the serum concentrations of albumin, creatinine, total protein, urea concentrations and the activity of renal nucleotidase with a reduction in the activity of glucose-6-phosphate dehydrogenase (G6PD) when compared to normal control (p < 0.05). Furthermore, renal tissue from the piroxicam alone treated group revealed a significant decrease in the activities of renal superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase as well as reduced glutathione with concomitant increase in lipid peroxidation and hydrogen peroxide generation. In addition, histological assessment of the renal tissue showed noticeable damage in piroxicam alone treated group. However, concomitant administration of TRECDS showed a dose-dependent reduction in the concentrations and the activity of the kidney markers with significant increase in the activities of G6PD and restores the antioxidant status of the kidney. The results show the nephroprotective potential of TREDS against piroxicam-induced renal damage.展开更多
基金supported by Atatürk University Scientific Research Projects Coordinatorship (BAP) with the project code 2021-8836。
文摘Objective:To investigate the effects of melatonin on renal inflammation,oxidative stress,apoptosis,as well as DNA and tissue damage in acrylamide-induced nephrotoxicity in rats.Methods:Fifty male rats were randomly divided into five groups.The control group received distilled water by gastric lavage for 11days and the acrylamide group was administered acrylamide(50 mg/kg,i.g.)for 11 days.The MEL10+ACR and MEL20+ACR groups received intraperitoneal melatonin 10 and 20 mg/kg,respectively,for 11 days,and acrylamide(50 mg/kg,i.g.)was administered 1h after melatonin injection.The MEL20 group was injected with melatonin(20 mg/kg)for 11 days.Kidney function tests were performed and biochemical and inflammatory parameters were determined.In addition,histopathological,immunohistochemical,and immunofluorescence examinations were carried out.Results:Melatonin significantly abated acrylamide-induced rise in serum urea and creatinine levels.Acrylamide caused oxidative stress,inflammation,apoptosis,as well as DNA and tissue damage in the kidneys.Melatonin treatment alleviated acrylamide-induced renal damage by exhibiting antioxidant,anti-inflammatory,and antiapoptotic effects.Moreover,melatonin significantly ameliorated acrylamide-caused histopathological changes in kidney tissue.Conclusions:Melatonin attenuates acrylamide-induced renal oxidative stress,inflammation,apoptosis,and DNA damage in rats.
基金This work was supported by the National Key R&D Program of China(Project No.2018YFC1602103)Ministry of Science and Technology of China.
文摘Emodin is an effective component of rhubarb with positive pharmacological effects on human health.However,it is also toxic to different cells or tissues to varying degrees.The effects of emodin on glomerular endothelial cells(GECs)remain to be tested,and the documented works were always performed in vitro and hardly reflect the real physiological situation.To study the effects of emodin on GECs in a biomimetic environment,we utilized a microfluidic chip to assess the physiological reaction of human renal glomerular endothelial cells to various concentrations of emodin in this work.The results showed that emodin caused cytotoxicity,impaired glomerular filtration barrier integrity to macromolecules,and increased barrier permeability in a dose-dependent manner.With the increase in emodin concentration,the concentration of the pro-inflammatory cytokine tumor necrosis factor-α,interleukin(IL)-6,transforming growth factor-β1,and monocyte chemoattractant protein(MCP-1)increased while the production of inflammatory cytokine IL-6 first increased and then decreased with the increase in emodin concentration.Our findings shed new light on emodin-induced nephrotoxicity and provide insights for the application of microfluidic chip devices to reveal drug-cell interactions.
文摘This paper analyzes the relationship between toxicity and safety of traditional Chinese medicine(TCM)based on the cases of current nephrotoxicity and hepatotoxicity,and summarizes the literature on hepatotoxicity and nephrotoxicity.It is found that the main reasons for the toxic reaction of TCM are own factors of drugs,irregular administration of medicine and individual difference.However,as long as the"quality"and"quantity"of TCM are guaranteed,the toxicity of TCM can be controlled within the safety range.
基金the National Natural Science Foundation of China(No.81473411).
文摘Licorice,one of the most widely used medicinal herbs in East Asia,has effects such as anti-inflammation,antioxidant,and detoxifying.This study aimed to evaluate the protective effect of licorice on brucine-induced nephrotoxicity.Sprague Dawley rats were administered with brucine intraperitoneally for 7 consecutive days with or without treatment with licorice.The content of blood urea nitrogen and creatinine in serum,the activities of superoxide dismutase and content of glutathione,malonaldehyde in kidney tissue were detected.Hematoxylin-eosin staining was employed to observe the histopathological changes of kidney.The expression and phosphorylation levels of protein were evaluated by Western blotting and immunohistochemical analysis.The results illustrated that treatment with licorice extracts(LE)significantly protected against the brucineinduced nephrotoxicity by reducing the content of blood urea nitrogen and serum creatinine,attenuating pathologic damage.The unbalance of oxidative stress was repaired by LE via increasing the level of glutathione,promoting the activities of superoxide dismutase and decreasing the content of malonaldehyde.In addition,LE overturned the influence of brucine on apoptosis-related protein and signal transducer and activator of transcription-3(STAT3)activation.Taken together,these data demonstrate that licorice may attenuate brucine-induced nephrotoxicity via inactivation of oxidative stress and mitochondrial-mediated apoptosis pathway.More importantly,the renoprotective effects may be mediated,at least partly,by preventing the activation of STAT3 protein.
文摘Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which was a mean of increasing their therapeutic index,reducing their toxicity and altering drug biodistribution.One of the challenges for preparing VANH-Lips is their low encapsulation efficiency(EE).In the present study,we aim to improve the liposomal formulation of VANH for higher EE,longer systemic circulation,reduced nephrotoxicity and enhanced antimicrobial activities.Vancomycin hydrochloride-loaded liposomes(VANH-Lips)were formulated by the method of modified reverse phase evaporation.Based on the optimization of formulation with orthogonal experimental design,the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78±2.56%and 188.4±2.77 nm.In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation.After intravenous injection to mice,the mean residence time(MRT)of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution(VANH-Sol)group.Furthermore,the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection.In conclusion,VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.
文摘Anticancer drug nephrotoxicity is an important and increasing adverse drug event that limits the efficacy of cancer treatment.The kidney is an important elimination pathway for many antineoplastic drugs and their metabolites,which occurs by glomerular filtration and tubular secretion.Chemotherapeutic agents,both conventional cytotoxic agents and molecularly targeted agents,can affect any segment of the nephron including its microvasculature,leading to many clinical manifestations such as proteinuria,hypertension,electrolyte disturbances,glomerulopathy,acute and chronic interstitial nephritis,acute kidney injury and at times chronic kidney disease.The clinician should be alert to recognize several factors that may maximize renal dysfunction and contribute to the increased incidence of nephrotoxicity associated with these drugs,such as intravascular volume depletion,the associated use of nonchemotherapeutic nephrotoxic drugs(analgesics,antibiotics,proton pump inhibitors,and bonetargeted therapies),radiographic ionic contrast media or radiation therapy,urinary tract obstruction,and intrinsic renal disease.Identification of patients at higher risk for nephrotoxicity may allow the prevention or at least reduction in the development and severity of this adverse effect.Therefore,the aim of this brief review is to provide currently available evidences on oncologic drug-related nephrotoxicity.
文摘Objective:To evaluate nephroprotective potential of Solarium xanthocarpum(S.xanthocarpum) fruit extract(SXE) against gentamicin(GM) induced nephrotoxicity) and renal dysfunction. Methods:Twenty-four Wistar rats were divided into four groups(n=6).Control rats that received normal saline(i.p.) and 0.5%carboxymethyl cellulose(p.o.) per day lor 8 d.Nephrotoxicity was induced in rats by intraperitoneal administration of GM(100 mg/kg/d for 8 d) and were treated with SXE(200 and 400 mg/kg/d(p.o.) for 8 d).Plasma and urine urea and creatinine,kidney weight,urine output,blood urea nitrogen,renal enzymatic and non-enzymatic antioxidants and lipid peroxidation was evaluated along with histopathological investigation in various experimental groupsof rats.Results:It was observed that the GM treatment induced significant elevation(P【0.001) in plasma and urine urea,creatinine,kidney weight,blood urea nitrogen, renal lipid peroxidation along with significant decrement(P【0.001) in urine output,renal enzymatic and non-enzymatic antioxidants.SXE 200 and 400 mg/kg treatment to GM treated rats recorded significant decrement(up to P【0.001) in plasma and mine urea and creatinine, renal lipid peroxidation along with significanl increment(up to P【0.001) in renal enzymatic and non-enzvmatic antioxidants.Histological obsenatioiis of kidney tissues too correlated with the biochemical obsenatioiis.Conclusions:These finding powerfully supports that S,xanthocarpum fruit extract acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM both in the biochemical and histopathological parameters and thus validates its elhnomedicinal use.
文摘Objective:To explore the possible effects of naringin on acrylamide-induced nephrotoxicity in rats.Methods:Sprague-Dawley rats weighing 200-250 g were randomly divided into five groups.The control group was given intragastric(i.g.)saline(1 mL)for 10 d.The acrylamide group was given i.g.acrylamide in saline(38.27 mg/kg titrated to 1 mL)for 10 d.The treatment groups were administered with naringin in saline(50 and 100 mg/kg,respectively)for 10 d and given i.g.acrylamide(38.27 mg/kg)1 h after naringin injection.The naringin group was given i.g.naringin(100 mg/kg)alone for 10 d.On day 11,intracardiac blood samples were obtained from the rats when they were under anesthesia,after which they were euthanized.Urea and creatinine concentrations of blood serum samples were analyzed with an autoanalyzer.Enzyme-linked immunosorbent assay was used to quantify malondialdehyde,superoxide dismutase,glutathione,glutathione peroxidase,catalase,tumor necrosis factor-α,nuclear factor-κB,interleukin(IL)-33,IL-6,IL-1β,cyclooxygenase-2,kidney injury molecule-1,mitogen-activated protein kinase-1,and caspase-3 in kidney tissues.Renal tissues were also evaluated by histopathological and immunohistochemical examinations for 8-OHdG and Bcl-2.Results:Naringin attenuated acrylamide-induced nephrotoxicity by significantly decreasing serum urea and creatinine levels.Naringin increased superoxide dismutase,glutathione,glutathione peroxidase,and catalase activities and decreased malondialdehyde levels in kidney tissues.In addition,naringin reduced the levels of inflammatory and apoptotic parameters in kidney tissues.The histopathological assay showed that acrylamide caused histopathological changes and DNA damage,which were ameliorated by naringin.Conclusions:Naringin attenuated inflammation,apoptosis,oxidative stress,and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats.
文摘This study aimed to assess the preventive effects of thyme oil and thymol on doxorubicin(DOX)-induced renotoxicity,cardiotoxicity,and oxidative stress in Wistar rats.Thyme oil was subjected to GC-MS analysis,which indicated that thymol was the major constituent representing 33.896%.Rats intraperitoneally injected with DOX at a dose of 2 mg/kg b.w./one per week for 7 weeks were co-treated with thyme oil and its major constituent,thymol,at doses 250 and 100 mg/kg b.w./every other day,respectively,by oral gavage for the same period.Thyme oil and thymol markedly ameliorated the raised levels of serum urea,uric acid,and creatinine in DOX-administered rats.They also reduced the elevated activities of serum CK-MB and LDH.Thyme oil was more effective than thymol in decreasing the elevated serum creatinine level and serum CK-MB activity in DOX-administered rats,thereby reflecting its more potent effect on kidney and heart functions.Lipid peroxidation significantly decreased while GSH level and GST and GPx activities significantly increased in kidney and heart of DOX-administered rats treated with thyme oil and thymol.The DOX-induced perturbed kidney histological changes including congestion of glomerulus tuft,inflammatory cells infiltration,protein cast in lumina of the renal tubule,and thickening of the parietal layer of Bowman’s capsule were remarkably ameliorated as a result of treatment with thyme oil and thymol;thyme oil was more effective.In addition,DOX-induced deleterious heart histological alterations,including intramuscular infiltration of inflammatory cells,focal necrosis of cardiac myocytes,and edema,were remarkably reduced by treatment with thyme oil and thymol.Thus,it can be concluded that DOX could induce marked toxicity in kidney and heart,and the treatment with thyme oil or thymol produced potential improvement of kidney and heart function and histological integrity via repression of oxidative stress and enhancement of antioxidant defense mechanisms.
基金supported by All India Council for Technical Education,New Delhi,India for providing JRF awarded grants(No.355118293)(GPAT-Exam)for the completion of M.Pharm research project
文摘Objective: To evaluate the nephroprotective effect of defatted mehtanolic extract and aqueous extract of Murraya koenigii against Cyclophosphamide drug. Methods: Nephrotoxicity was induced by Cyclophosphamide in 7 d at 150 mg/kg body weight through intraperitoneal route in rat model. Nephroprotective activity of Murraya koenigii(M. koenigii) extract(100 mg/kg and 200 mg/kg in intraperitoneal route) was measured, including nephrological source, oxidative stress parameters like superoxide dismutase, glutathione, the lipid peroxide and in vivo assay like blood urea nitrogen, creatinine were determined and analyzed by One way analysis of variance followed by Tukey's test. Results: The study result showed that important phytochemicals such as carbohydrates, flavonoids, tannin, alkaloids, glycosides, protein and steroids were found to be present in the extract of M. koenigii. The renal function markers like blood urea nitrogen and ceatinine level were found to be decreased significantly by M. koenigii extract treatment. A significant difference was found to be at P<0.01. Conclusions: The present study reveals the protective role of M. koenigii extract against Cyclophosphamide induced nephrotoxicity.
文摘Cyclosporine (CsA) has revolutionized transplant medicine and is currently one of the most important immunosuppressive agents for a wide range of organ transplantations and of autoimmune and inflammatory diseases, such as rheumatoid arthritis, uveitis, psoriasis, and atopic dermatitis. Renal impairment represents the main limitation to CsA long-term continuous therapy. However, it has been shown that nephrotoxicity is associated with longer treatment duration, larger cumulative doses and higher daily dose of CsA. With low dose regimens (<5 mg/kg/day), stable serum creatinine levels have been observed up to 15-20 years after kidney transplantation. Intermittent therapy may offer a good therapeutic strategy to limit long-term renal dysfunction, given the fact that renal structural changes are dose- and time-dependent. The best predictor of permanent renal damage is a persistent increase in serum creatinine level one month after treatment withdrawal. In patients with autoimmune diseases, the percentage increase in serum creatinine above baseline value during CsA therapy has been shown to predict CsA-induced nephropathy. Before CsA therapy initiation, patients should undergo a thorough baseline evaluation including laboratory assessments, in particular electrolytes, serum creatinine, and urea levels. Furthermore, patients should be evaluated for factors that might increase the risk of nephrotoxicity, such as obesity, older age, hypertension, concomitant use of nephrotoxic drugs, and pre-existing renal conditions. In the present paper, CsA-induced nephropathy will be reviewed in terms of pathophysiology, pathologic and clinical findings, and strategies for prevention and management.
文摘Objective:To investigate the antioxidant ef ect of an orally administered ethanol extract of nettle(Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin-induced nephrotoxicity in male rabbits. Methods: Twenty rabbits were divided into 4 equal groups:(G1) control group,(G2) gentamicin treated group(100 mg/kg),(G3) nettle treated group(100 mg/kg),(G4) combination treated group with both gentamicin(100 mg/kg) and nettle(100 mg/kg) for 10 days. The antioxidant properties of nettle were evaluated using dif erent antioxidant tests, such as determination of glutathione and malondialdehyde levels and total phenolic content analysis. Results: Biochemical and histopathological study revealed that gentamicin caused nephrotoxicity observed clearly in the histopathological section of the kidney in the gentamicin treated group. Serum creatinine and blood urea nitrogen were biochemical indicators for nephrotoxicity which increased signii cantly in gentamicin treated group; other groups have no signii cant change in these two parameters. Nettle extract protected the rabbits from alteration in the level of blood urea nitrogen and serum creatinine when given after inducing of gentamicin nephrotoxicity. The nettle treated group showed a great ef ect as an antioxidant factor by increasing the glutathione level and reducing malondialdehyde level. No signii cant changes in biochemical parameters and no renal histopathological changes observed in the groups treated with nettle extract, which meant nettle had powerful antioxidant activity. Conclusions: Therefore, it can be assumed that the nephroprotective ef ect shown by nettle in gentamicin-induced nephrotoxicity can reserve intracellular levels of biological pathways and supportively enhance excretion of toxic levels of gentamicin.
基金supported by Chairman,Mother Mary education Society,Vikas nagar,Hyderabad,Andhra Pradesh,India
文摘Objective:To highlight the nephroprotective activity of ethyl acetate extract of dried flowers of Tecomu stans for its protective effects on genlamicin-induced nephrotoxicity in albino rats. Methods:For studying acute toxicity study,single oral dose of 5（KM） mg ethyl acetate floral extract/kg hodv weight was administered to albino rats（five females,five males）.Nephrotoxicity was induced in albino rats by intraperitoneal administration of gentamicin 80 mg/kg/day for eight days.Effect of concurrent administration of ethyl acetate floral extract of Tecoma stans at a dose of 100.200 and 300 mg/kg/day given by oral mute was determined using serum creatinine,serum uric acid,blood urea nitrogen and serum urea as indicators of kidney damage.The study groups contained six rats in each group.As nephrotoxicity of gentamicin is known to involve induction of oxidative stress,in vitro antioxidant aclivity and free radical-scavenging activity of this extract was also evaluated.Results:For acute toxicity testing both female and male rats administered with the extract at a dose of 5 000 mg/kg.The results showed no toxicity in terms of general behavior change,mortality,or change in gross appearance of internal organs(LD<sub>50</sub>】5 000 mg/kg). It was observed that the ethyl acetate floral extract of Tecoma stans significantly protected rat kidneys from gentamicin-induced histopathological changes.Gentamicin-induced glomerular congestion,peritubular and blood vessel congestion,epithelial desquamation,accumulation ol inflamnialoiy cells and necrosis of the kidney cells were found to be reduced in the groups receiving the ethyl acetate floral extract of Tecoma starts along with gentamicin in a dose dependent manner.The floral extract also reduced the gentamicin-induced increase in serum creatinine,serum uric acid,blood urea nitrogen and serum urea levels（P】0.01）.Conclusions: The present study indicates a verv important role of reactive oxygen species（BOS） and the relation to renal dysfunction and point to the therapeutic potential of Tecoma stans in gentamicin induced nephrotoxicity.
文摘Aim Ethnopharmacological relevance： Ribes diacanthum Pall. （Saxifragaceae） , a Mongolian folk me- dicinal plant, was used to treat urinary system diseases. The present work aims to investigate the protective effects of Ribes diacanthum Pall （RDP） against cisplatin-induced nephrotoxicity. Methods The renal injury was mod- eled by intraperitoneal injection of cisplatin for 5 consecutive days （5 mg·kg^-1 ）. Nephroprotection of RDP was investigated by oral administration of RDP aqueous extract at a daily dose of 40 mg · kg^- 1 for 14 consecutive days, starting 7 days prior to cisplatin administration. Results We demonstrated that pretreatment with RDP aqueous ex- tract protected the mice from death induced by cisplatin administration. RDP treatment also significantly reduced blood urea nitrogen （BUN） and serum creatinine （Cr） levels observed in cisplatin-administrated mice. Histopatho- logical analysis demonstrated that RDP administration protected cisplatin-induced renal tubular cell apoptosis. Fur- ther western blotting analysis revealed that RDP significantly reversed cisplatin-increased expression levels of cleaved-Caspase-3, Bax and cisplatin-decreased expression level of Bcl-2 in renal tissue. Finally, RDP markedly enhanced enzyme activities of reduced superoxide dismutase （SOD）, Heine oxygenase 1 （HO-1） and catalase （CAT）, suppressed lipid peroxidation as well as reactive oxygen species （ROS） production. Conclusion We concluded that RDP displayed nephroprotective effects against cisplatin-induced renal tubular cell apoptosis, possi- bly associated with both enhanced antioxidase activity and suppressed ROS generation. Given the major nephrotox- icity of cisplatin cancer chemotherapy, RDP might be a potential candidate for neoadjuvant chemotherapy.
文摘Objective: To investigate the effects of probiotic bacteria on cisplatin(CP)-induced nephrotoxicity. Methods: In the present study, 50 Sprague-Dawley rats were used and randomly divided into five groups including control, CP, probiotic bacteria treatment groups with different doses(0.5 and 1 mL) and only probiotic bacteria group. After CP and probiotic administration on seven days, rats sacrificed under anesthesia on the eighth day. The serum urea, creatinine, and blood urea nitrogen levels were analyzed. In renal tissue, malondialdehyde levels, superoxide dismutase and glutathione activity, interleukin-8, interleukin-1β and tumor necrosis factor-alpha levels were determined and histopathological and immunohistochemical changes were also examined. Results: According to results, urea, creatinine and blood urea nitrogen levels as well as kidney weights increased in CP group. Also, CP induced inflammation, oxidative stress, DNA damage and apoptosis in kidney tissue and caused histopathological changes. Administration of the high dose of probiotic bacteria could prevent these changes and damages. Conclusions: This study reveals that probiotic bacteria has protective effects on CP-induced renal damage in rats.
基金financially supported by the grants of Bu-Ali Sina University
文摘Objective: To investigate nephroprotective potential of Meristotropis xanthioides(M.xanthioides) extract against ethanol-induced nephrotoxicity in Wistar rats, and also its total phenolics content, antioxidant and antibacterial activities.Methods: Total phenol and flavonoid amounts of the leaf and stem extracts were determined by Folin–Ciocalteu and aluminum chloride reagents, respectively.Antioxidant and antibacterial activities of the extracts were investigated by 2,2-diphenyl-1-picrylhydrazyl radical scavenging and disc diffusion methods, respectively.In addition,protective potential of the leaf extract against ethanol-induced nephrotoxicity was studied by histological and biochemical analyses.Results: Obtained results indicated high total phenol [(10.26 ± 0.46) mg GAE/g of dry extract] and flavonoid [(3.63 ± 0.62) mg QE/g of dry extract] amounts in the leaf extract.The leaf and stem extracts possessed stronger antioxidant activity [IC_(50):(0.119 ± 0.006)mg/mL and IC_(50):(0.133 ± 0.009 mg/mL)] than that of ascorbic acid [IC_(50):(0.142 ± 0.002)mg/mL].Also, the extracts showed good antibacterial activity against the most of bacteria taken in this research, especially Gram-positive ones.Histological examinations revealed tissue injury in the kidney of rats treated with ethanol.Results from biochemical assays showed reduction in total protein content and also in superoxide dismutase activity.In addition, remarkable increased levels(P < 0.05) of H_2O_2 and malondialdehyde were found in ethanol-treated rats in comparison to control group.However, these injuries were significantly improved in rats treated by M.xanthioides leaf extract.Conclusions: Results from present study demonstrates strong pharmaceutical potential of M.xanthioides extract to apply as a new drug supplement.
文摘Tisplatin is one of the valuable icancer agents against several types of neoplasm. However, nephrotoxicity is the major adverse effect representing in cisplatin therapy. In this study, the animal tests detecting protective effects of a natural compound, Decursin, on cisplatin-induced nephrotoxicity were examined by using in vivo model. Pretreatment Decursin 10, 20 and 40 mg · kg-1 at 48, 24 and 6 h, and administration of a single dose of Cisplatin 5.2 mg · kg-1. Nephrotoxicity was evaluated by serum BUN and creatinine examination. There was significant difference in body weights, serum BUN and creatinine levels of the normal group. Based on the new understanding of the protective mechanisms of cisplatin-induced nephrotocivity, new strategies can be developed to prevent renal injury or to enhance recovery after cisplatin treatment.
基金This work was supported by Cumhuriyet University Scientific Research Projects Coordination Unit(CUBAP,Sivas,Turkey,Grant No.V-087).
文摘Side effects of cisplatin,especially dose-dependent nephrotoxicity,are major factors limiting its use in cancer.Boldine((S)-2,9-dihydroxy-1,10-dimethoxy-aporphine)is a natural alkaloid known for its strong antioxidant activity present in leaves/bark of boldo tree(Peumus boldus Molina),a native tree in Chile.Here,we aimed to investigate the nephroprotective effect of boldine and its underlying mechanisms on cisplatin-induced rat renal injury.Thirty Wistar albino rats divided into 5 groups(Control,Cis,Bold.40,Cis+Bold.20,Cis+Bold.40 groups)were used.Rats received boldine(20 or 40 mg/kg/day),or vehicle(saline)intraperitoneal for 14 days and a single dose cisplatin(7 mg/kg,ip)was applied on the 10th day to induce nephrotoxicity.Rats and kidney tissue were weighed to determine kidney index.Blood urea nitrojen(BUN)and creatinine levels,the amount of thiobarbituric acid reactive substances(TBARS,an index of lipid peroxidation),superoxide dismutase(SOD),glutathione peroxidase(GPx)enzyme activities and tumor necrosis factor alpha(TNF-α)levels were measured and histopathologic examination was performed.Inducible nitric oxide synthase(iNOS)and caspase-3 expressions were detected immunohistochemically.Nephrotoxicity induced by cisplatin was apparent by elevated levels of BUN,creatinine,kidney index,TBARS and TNF-α,and decreased body weight,SOD and GPx enzyme levels.Pretreatment with boldine protected the renal function at both boldine doses by fixing the renal damage markers,oxidative stress,caspase-3 and iNOS expression.Histopathological findings supported biochemical findings.Taken together these findings indicate that boldine has promising protective effect against cisplatin nephrotoxicity by improving oxidative stress,inflammation,histopathological alterations and by alleviating caspase 3 expression.
基金Supported by The Hunan Province Natural Science Foundation,No.2022JJ80043Nature Science Foundation of Changsha,No.kq2014268+1 种基金Hunan Engineering Research Center of Intelligent Prevention and Control for Drug Induced Organ Injury,No.40Scientific Research Fund Project of Hunan Pharmaceutical Society,No.2020YXH010.
文摘BACKGROUND Polymyxin-induced nephrotoxicity is a major safety concern in clinical practice due to long-term adverse outcomes and high mortality.AIM To conducted a systematic review and meta-analysis of the prevalence and potential predictors of polymyxin-induced nephrotoxicity in adult intensive care unit(ICU)patients.METHODS PubMed,EMBASE,the Cochrane Library and Reference Citation Analysis database were searched for relevant studies from inception through May 30,2022.The pooled prevalence of polymyxin-induced nephrotoxicity and pooled risk ratios of associated factors were analysed using a random-effects or fixed-effects model by Stata SE ver.12.1.Additionally,subgroup analyses and meta-regression were conducted to assess heterogeneity.RESULTS A total of 89 studies involving 12234 critically ill adult patients were included in the meta-analysis.The overall pooled incidence of polymyxin-induced nephrotoxicity was 34.8%.The pooled prevalence of colistin-induced nephrotoxicity was not higher than that of polymyxin B(PMB)-induced nephrotoxicity.The subgroup analyses showed that nephrotoxicity was significantly associated with dosing interval,nephrotoxicity criteria,age,publication year,study quality and sample size,which were confirmed in the univariable meta-regression analysis.Nephrotoxicity was significantly increased when the total daily dose was divided into 2 doses but not 3 or 4 doses.Furthermore,older age,the presence of sepsis or septic shock,hypoalbuminemia,and concomitant vancomycin or vasopressor use were independent risk factors for polymyxin-induced nephrotoxicity,while an elevated baseline glomerular filtration rate was a protective factor against colistin-induced nephrotoxicity.CONCLUSION Our findings indicated that the incidence of polymyxin-induced nephrotoxicity among ICU patients was high.It emphasizes the importance of additional efforts to manage ICU patients receiving polymyxins to decrease the risk of adverse outcomes.
文摘Piroxicam is commonly used as anti-inflammatory and pain relieving drug;however, its side effects include fluid retention, renal damage and heart failure. This study aimed at evaluating the nephroprotective role of different doses of the tannin-rich extract of Chasmanthera dependens stem (TRECDS) on piroxicam-induced nephrotoxicity in adult male Wistar rats. Thirty-two adult rats were divided into four groups of eight rats per group and treated orally for ten days. Rats in group one received 0.5 ml normal saline (0.9% v/v) and served as normal control group. Rats in group two received 20 mg/kg body weight piroxicam alone. Rats in groups three and four received 20 mg/kg body weight of piroxicam with concomitant administration of 200 and 400 mg/kg body weight of TRECDS. At the expiration of the experiment, rats were sacrificed and the kidney was removed. Renal function was evaluated. The results showed that administration of piroxicam alone caused a significant elevation in the serum concentrations of albumin, creatinine, total protein, urea concentrations and the activity of renal nucleotidase with a reduction in the activity of glucose-6-phosphate dehydrogenase (G6PD) when compared to normal control (p < 0.05). Furthermore, renal tissue from the piroxicam alone treated group revealed a significant decrease in the activities of renal superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase as well as reduced glutathione with concomitant increase in lipid peroxidation and hydrogen peroxide generation. In addition, histological assessment of the renal tissue showed noticeable damage in piroxicam alone treated group. However, concomitant administration of TRECDS showed a dose-dependent reduction in the concentrations and the activity of the kidney markers with significant increase in the activities of G6PD and restores the antioxidant status of the kidney. The results show the nephroprotective potential of TREDS against piroxicam-induced renal damage.
