BACKGROUND:Although the use of non-heart beating donors(NHBDs)could bridge the widening gap between organ demand and supply,its application to liver transplantation is limited due to the high incidence of primary graf...BACKGROUND:Although the use of non-heart beating donors(NHBDs)could bridge the widening gap between organ demand and supply,its application to liver transplantation is limited due to the high incidence of primary graft loss.Prevention of liver injury in NHBDs will benefit the results of transplantation.This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS:One hundred and four Wistar rats were randomly divided into 7 groups:normal control(n=8) controls 1,2 and 3(C1,C2,C3,n=16),and experimenta 1,2 and 3(E1,E2,E3,n=16).For groups C1 and E1,C2 and E2,and C3 and E3,the warm ischemia time was 0,30,and 45 minutes,respectively.Liver grafts were flushed with and preserved in 4℃Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group Recipients of each experimental group were injected with L-arginine(10 mg/kg body weight)by tail vein 10 minutes before portal vein reperfusion.Donors and recipients of each experimental control group were treated with norma saline.Then transplantation was performed.At 1,3,and 24 hours after portal vein reperfusion,blood samples were obtained to determine the levels of alanine aminotransferase (ALT),aspartate aminotransferase(AST),nitric oxide (NO)and plasma endothelin(ET).At 3 hours after porta vein reperfusion,grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation.RESULTS:At 1 hour after portal vein reperfusion,the levels of NO in groups E1,E2,E3 and C1,C2,C3 were lower,while the levels of plasma ET,serum ALT and AST were higher than those in the normal control group(P<0.05).At 1,3,and 24 hours,the levels of NO in groups E1,E2,E3 were higher,while the levels of plasma ET,serum ALT and AST were lower than those in the corresponding control groups(C1,C2,C3) (P<0.05).The levels of NO in groups C2 and C3 were lower than in group C1(P<0.05),and the level of NO in group C3 was lower than in group C2(P<0.05).At 1,3 and 24 hours, the levels of plasma ET,serum ALT,and AST in groups E1, E2,E3 were lower than those in the corresponding control groups(C1,C2,C3)(P<0.05).The levels of plasma ET,serum ALT,and AST were lower in group C3 than in groups C1 and C2(P<0.05).Pathological changes in groups E1,E2,E3 were milder than those in the corresponding experimental control groups(C1,C2,C3). CONCLUSIONS:The imbalance between NO and ET plays an important role in the development of ischemia- reperfusion injury of liver grafts from NHBDs.L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.展开更多
Background:Prenatal nutrition is crucial for embryonic development and neonatal growth,and has the potential to be a main determinant of life-long health.In the present study,we used a layer chick model to investigate...Background:Prenatal nutrition is crucial for embryonic development and neonatal growth,and has the potential to be a main determinant of life-long health.In the present study,we used a layer chick model to investigate the effects of in ovo feeding(IOF)of L-arginine(Arg)on growth,intestinal development,intestinal microbiota and metabolism.The treatments included the non-injected control,saline-injected control,and saline containing 2,6,or 10 mg Arg groups.Results:IOF Arg increased early intestinal index and villus height,and enhanced uptake of residual yolk lipid,contributing to subsequent improvement in the early growth performance of chicks.Prenatal Arg supplementation also increased the early microbialα-diversity,the relative abundance of Lactobacillales and Clostridiales,and decreased the relative abundance of Proteobacteria of cecum in chicks.Furthermore,the shift of cecal microbiota composition and the colonization of potential probiotics were accelerated by IOF of Arg.Simultaneously,metabolomics showed that metabolisms of galactose,taurine-conjugated bile acids and lipids were modulated to direct more energy and nutrients towards rapid growth of intestine at the beginning of post-hatch when embryos received IOF of Arg.Conclusions:Prenatal Arg supplementation showed beneficial effects on the early intestinal development,cecal microbiota and host metabolism of layer chicks,contributing to subsequent improvement in the early growth performance.These findings provide new insight into the role of IOF of Arg in the establishment of the gut microbiota of newly-hatched layer chicks,and can expand our fundamental knowledge about prenatal nutrition,early bacterial colonization and intestinal development in neonate.展开更多
BACKGROUND: Post-transplantation pancreatitis andgraft thrombosis are two major complications of pancreastrans-plantation that contribute to morbidity, mortality, andgraft loss. Nitric oxide (NO) is a potent vasodilat...BACKGROUND: Post-transplantation pancreatitis andgraft thrombosis are two major complications of pancreastrans-plantation that contribute to morbidity, mortality, andgraft loss. Nitric oxide (NO) is a potent vasodilator agentformed when L-arginine ( L-Arg) is converted to L-citrul-line by the action of NO synthase (NOS), and plays a ma-jor role in microcirculatory changes. We therefore investi-gated the effect of L-Arg on reperfusion injury followingpancreaticoduodenal transplantation in rats.METHODS: The homologous male Wistar rat model ofheterotopic total pancreaticoduodenal transplantation wasused. The L-Arg-treated rats received the intravenous in-jection of L-Arg 5 minutes before and after reperfusion at adose of 200 mg/kg while the N-Nitro-L-arginine methyl es-ter (L-NAME) -treated rats at a dose of 10 mg/kg. Theamount of NO in the pancreas graft was measured. Serumconcentration of cytokine-induced neutrophil chemoattrac-tant ( CINC) was determined by enzyme-linked immu-nosorbant assay, the expression of CINC mRNA was detect-ed by Northern blot assay in the pancreas graft, and the ac-tivity of myeloperoxidase (MPO) was measured. Histolo-gical examination was performed.RESULTS: The amount of NO was higher in the L-Arggroup than in the control group, while it was lower in theL-NAME group than in the control group (P <0.05). Thepeak of serum CINC concentration occurred 3 hours afterreperfusion with the difference among the groups being sig-nificant. The expression peak of CINC mRNA in the pan-creas graft occurred 3 hours after reperfusion. The expres-sion level in the L-Arg group (7.66 ± 1.53 μg/L) was lowerthan in the control group (26.31±2.01 μg/L), while in theL-NAME group (34.18 ±3.12 μg/L) it was higher than thatin the control group (P <0. 05). The activity of MPO inthe L-Arg group was obviously decreasd as compared within the other groups. The pancreas inflammation was ame-liorated when L-Arg was administered, whereas the panc-reas damage was aggravated when L-NAME was adminis-tered.CONCLUSIONS: L-Arg can increase the amount of NOand inhibit the elevation of CINC, the CINC mRNA ex-pression and early neutrophil accumulation in the pancreas.NO has protective effects on ischemia/reperfusion injury inpancreaticoduodenal transplantation.展开更多
Background: Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposi...Background: Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposition in high fat diet-fed Nile tilapia(Oreochromis niloticus).Results: In the present study, we found that dietary supplementation with 1% or 2% arginine decreased the deposition and concentration of fats in the liver;the concentrations of triglycerides, low-density lipoprotein, total cholesterol, and high-density lipoprotein in the serum;and the diameter of adipocytes in intraperitoneal adipose tissue. Compared with the un-supplementation control group, the hepatic activities of alanine aminotransferase,aspartate aminotransferase, and lactate dehydrogenase, and hepatic concentration of malondialdehyde were reduced but these for catalase and superoxide dismutase were enhanced by dietary supplementation with 2% arginine. Arginine supplementation reduced the total amounts of monounsaturated fatty acids, while increasing the total amounts of n-3 and n-6 polyunsaturated fatty acids in the liver. These effects of arginine were associated with reductions in mRNA levels for genes related to lipogenesis(sterol regulatory element-binding protein-1, acetyl-CoA carboxylase α, stearoyl-CoA desaturase, and fatty acid synthase) but increases in mRNA levels for genes involved in fatty acid β-oxidation(carnitine palmitoyltransferase 1α and peroxisome proliferator-activated receptor α). In addition, hepatic mRNA levels for Δ4 fatty acyl desaturase 2 and elongase 5 of very long-chain fatty acids were enhanced by arginine supplementation.Conclusion: These results revealed that dietary L-arginine supplementation to tilapia reduced high fat diet-induced fat deposition and fatty acid composition in the liver by regulating the expression of genes for lipid metabolism.展开更多
In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was developed.As such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis.Various proc...In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was developed.As such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis.Various processing methods were used to manufacture highdose formulation batches consisting various amounts of ARG and excipients.The formulations were evaluated using several analytical methods to assess suitability for further investigation.Several batches had enhanced in vitro aerolization properties.Significant future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs.展开更多
AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system involvement.METHODS Male Wistar rats underwent superior anterior pancreati...AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system involvement.METHODS Male Wistar rats underwent superior anterior pancreaticoduodenal vein(SAPDV)-ligation and were treated with a bath at the ligated SAPDV site(BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 m L bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation(filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein(IAPDV) and superior mesenteric vein(SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO-and oxidative stress [malondialdehyde(MDA)]-levels in duodenum.RESULTS Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues.CONCLUSION BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, aneffect related to the NO system and reduction of free radical formation.展开更多
AIM To study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide(NO) system agents.METHODS Alongside with the agents' application(after 1 min, medication(/kg, 10 ml/2 min bath/rat) includes...AIM To study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide(NO) system agents.METHODS Alongside with the agents' application(after 1 min, medication(/kg, 10 ml/2 min bath/rat) includes: BPC 157(10 μg), L-NAME(5 mg), L-arginine(100mg) alone or combined, and saline baths(controls)) on the rat perforate cecum injury, we continuously assessed the gross reappearance of the vessels(USB microcamera) quickly propagating toward the defect at the cecum surface, defect contraction, bleeding attenuation, MDA-and NO-levels in cecum tissue at 15 min, and severity of cecum lesions and adhesions at 1 and 7 d. RESULTS Post-injury, during/after a saline bath, the number of vessels was significantly reduced, the defect was slightly narrowed, bleeding was significant and MDA-levels increased and NO-levels decreased. BPC 157 bath: the vessel presentation was markedly increased, the defect was noticeably narrowed, the bleeding time was shortened and MDA-and NO-levels remained normal. L-NAME: reduced vessel presentation but not more than the control, did not change defect and shortened bleeding. L-arginine: exhibited less vessel reduction, did not change the defect and prolonged bleeding. In combination, mutual counteraction occurred(L-NAME + L-arginine) or the presentation was similar to that of BPC 157 rats(BPC 157 + L-NAME; BPC 157 + L-arginine; BPC 157 + L-NAME + L-arginine), except the defect did not change. Thereby at day 1 and 7, saline, L-NAME, L-arginine and L-NAME + L-arginine failed(defect was still open and large adhesions present). CONCLUSION The therapeutic effect was achieved with BPC 157 alone or in combination with L-NAME and L-arginine as it was able to consolidate the stimulating and inhibiting effects of the NO-system towards more effective healing recruiting vessels.展开更多
A 2 × 2 factorial arrangement was designed to test effects of supplementation of a low (L, 75 mg/kg BW) vs. high (H, 150 mg/kg BW) L-arginine given at early (first 56 days) vs. late (last 56 days) pregnancy on ma...A 2 × 2 factorial arrangement was designed to test effects of supplementation of a low (L, 75 mg/kg BW) vs. high (H, 150 mg/kg BW) L-arginine given at early (first 56 days) vs. late (last 56 days) pregnancy on maternal hormones and neonatal traits. Thirty Najdi pregnant ewes were randomly allocated into 6 groups. Ewes in G1 and G2 served as controls (C), given 50 ml saline at either early (CE) or late (CL) pregnancy, respectively. G3 and G4 ewes in early pregnancy received low (LE) and high L-arginine (HE), respectively. G5 and G6 ewes in late pregnancy received low (LL) and high (HL) L-arginine, respectively. A weekly blood sample was collected from initiation of the treatment till parturition. Serum growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin, progesterone (P4) and estradiol 17 β (E2) profiles were determined. Neonatal traits were also determined. Insulin was higher (P 0.05). Lamb survival rates at birth in LE ewes were highest (100%) compared to other treatments. In conclusion, supplementing pregnant ewes with low dosage of L-arginine at early stage of gestation increased lamb birth weight and survival, and improved maternal health.展开更多
AIM: To study the benef icial effects of triterpene α,β-amyrin and the underlying mechanisms in an experimental pancreatitis model. METHODS: Acute pancreatitis was induced in five groups of rats (n = 8) by L-arginin...AIM: To study the benef icial effects of triterpene α,β-amyrin and the underlying mechanisms in an experimental pancreatitis model. METHODS: Acute pancreatitis was induced in five groups of rats (n = 8) by L-arginine (2 × 2.5 g/kg, intraperitoneal, 1 h apart) and 1 h later, they received a single oral dose of α,β-amyrin (10, 30 and 100 mg/kg),methylprednisolone (30 mg/kg) and vehicle (3% Tween 80). A saline (0.9% NaCl) treated group served as a normal control. Efficacy was assessed at 24 h by determination of serum levels of amylase, lipase and proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-6], pancreatic myeloperoxidase (MPO) activity, lipid peroxidation [thiobarbituric acid reactive substances (TBARS)], nitrate/nitrite levels, and the wet weight/body weight ratio. Tissue histology and the immunoreactivity for TNF-α and inducible nitric oxide synthetase (iNOS) were performed. RESULTS: α,β-amyrin and methylprednisolone treatments significantly (P < 0.05) attenuated the L-arginine-induced increases in pancreatic wet weight/body weight ratio, and decreased the serum levels of amylase and lipase, and TNF-α and IL-6, as compared to the vehicle control. Also, pancreatic levels of MPO activity, TBARS, and nitrate/nitrite were signifi cantly lower. Histological f indings and TNF-α and iNOS immunostaining further confirmed the amelioration of pancreatic injury by α,β-amyrin. CONCLUSION: α,β-amyrin has the potential to combat acute pancreatitis by acting as an anti-in? ammatory and antioxidant agent.展开更多
Hepatic injury can be induced by the administration of carbon tetrachloride (CCl4) via the production of free radicals. The present work was initiated to investigate the kidney response to hepatic injury induced by CC...Hepatic injury can be induced by the administration of carbon tetrachloride (CCl4) via the production of free radicals. The present work was initiated to investigate the kidney response to hepatic injury induced by CCl4 and its treatment by L-arginine. Female Swiss albino mice were supplied with L-arginine for 6 days (orally, 200 mg/kg body weight) prior or post to hepatic injury induction through i.p. injection with a single dose of CCl4 (20 mg/kg body weight) for 24 h. After hepatic injury induction, renal MDA content was significantly elevated while renal GSH level and the activities of antioxidant enzymes (GR, GPx, GST, catalase, and SOD) were significantly decreased. These results suggest that CCl4 not only induces hepatic injury but also induces kidney dysfunction side by side. Following the treatment with L-arginine, all levels were almost back to normal. Therefore, Larginine administration is found to be an effective protector of both liver and kidney against CCl4-intoxication.展开更多
The heavy lanthanide ions（Dy,Ho,Er,Tm and Yb）were used to probe the conformation of L-arginine inaqueous solution.The results showed that the contact contribution to the observed<sup>13</sup>C paramagnet...The heavy lanthanide ions（Dy,Ho,Er,Tm and Yb）were used to probe the conformation of L-arginine inaqueous solution.The results showed that the contact contribution to the observed<sup>13</sup>C paramagnetic shift is verysmall for nuclei four or more bonds away from the bound lanthanide ion and it is significant for those in closeproximity to the lanthanide ion.The overall conformation of L-arginine was established by fitting the calculatedgeometric factors for the corresponding experimental data.In the lanthanide-L-arginine complex,the wholebackbone of the ligand is located outsite the zero-dipolar shift cone of the lanthanide ion with the carboxyl groupselectively coordinated to the metal.The calculated RE-O distance is 0.21 nm for the bidentate coordinationmode and the ligand is in an extended conformation in the solution with the molecular backbone corresponding tothe trans form.展开更多
BACKGROUND: There is much debate over the regulation of mitochondrial calcium overload and reducing the impairment of energy metabolism in hepatic cells. It has not been reported whether L-arginine (L-Arg) can affect ...BACKGROUND: There is much debate over the regulation of mitochondrial calcium overload and reducing the impairment of energy metabolism in hepatic cells. It has not been reported whether L-arginine (L-Arg) can affect hepatic mitochondrial calcium overload. This study was undertaken to investigate the protective effect of L-Arg on Ca2+ handling of hepatic mitochondrion in rats with obstructive jaundice and to clarify its possible mechanism. METHODS: Seventy-two male SD rats were randomly divided into 3 groups: sham operation+normal saline group (SO group), common bile duct ligation+normal saline group (BDL group), and common bile duct ligation+ L-Arg group (L-Arg group). The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and Ca2+ in rat hepatic mitochondrion were examined at the 7th, 14th and 21st day after operation. RESULTS: The Ca2+ and MDA levels of hepatic mitochondrion increased significantly but their SOD content decreased markedly at each time point in the BDL group. Except at the 21st day, the Ca2+ and MDA, contents of hepatic mitochondrion were significantly lower, and SOD concentrations were higher in the L-Arg group than those in the BDL group at the 7th and 14th day (P【0.01). CONCLUSION: L-Arg has a protective effect on mitochondrion in the early and mid stages of obstructive jaundice.展开更多
Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics.The newly emerging role of nitric oxide(NO)to conquer drug resistance has been recognized as a potential strategy.However,it remains...Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics.The newly emerging role of nitric oxide(NO)to conquer drug resistance has been recognized as a potential strategy.However,it remains a great challenge to realize targeted delivery as well as accurate release of NO at desired sites.Herein,we developed a PEGylated indocyanine green(m PEG-ICG)integrated nanovesicle system(PIDA)to simultaneously load doxorubicin hydrochloride(DOX·HCl)and the NO donor L-arginine(L-Arg),which can produce NO triggered by NIR light irradiation and exert multimodal therapy to sensitize drug-resistant cancers.Upon 808 nm irradiation,the NO released from PIDA led to a decrease in mitochondrial membrane potential,an increase in ROS and significant ATP depletion in K562/ADR cells,thus inhibiting cell growth and resolving the problem of drug resistance.Consequently,the in vivo experiment on K562/ADR-bearing nude mice indicated that PIDA nanovesicles achieved significant anticancer efficacy with a tumor inhibition rate of 80.8%.Above all,PIDA nanovesicles offer guidance for designing nanoplatforms for drug-resistant cancer treatment.展开更多
Objective:To evaluate the levels of estrogen,albumin and gonadotropins(luteinizing hormone,follicle-stimulating hormone)as well as the activity of dopamine beta hydroxylase(DAβH)in aged female rats treated with nitri...Objective:To evaluate the levels of estrogen,albumin and gonadotropins(luteinizing hormone,follicle-stimulating hormone)as well as the activity of dopamine beta hydroxylase(DAβH)in aged female rats treated with nitric oxide precursor L-arginine and neuronal nitric oxide synthase antagonist L-NAME.Methods:A total of 224 Wistar rats(36 weeks old,weighing 250 g)based on a random sampling were divided into the control and experimental groups after Pap smear test.The control group received only saline(1 mL/kg)intraperitoneally(i.p.).The experiential groups were treated with L-arginine(5,25 and 50 mg/kg,i.p.)and L-NAME(5 and 25 mg/kg,i.p.)for 3 to 21 days,once a day.Blood samples were taken from the rats and the levels of estrogen and albumin and gonadotropins in the serum were monitored by enzyme-linked immunosorbent assay kit,and the ovaries were examined immunohistopathologically for DAβH activity.Results:L-arginine(5 mg/kg)significantly increased estrogen level(P<0.05),which was associated with DAβH activation in the ovaries.L-NAME reduced this effect when administered prior to L-arginine dose.L-arginine caused no significant change in the levels of luteinizing hormone and follicle-stimulating hormone.Except for the lowest dose of L-arginine in the shortest period,albumin levels significantly decreased in other treatments compared to the control group(P<0.05).Conclusions:L-arginine is likely to reduce postmenopausal problems due to an increased nitric oxide level.展开更多
基金a grant from the Science & Technology Development Foundation of Guangdong Health Bureau(No.2006345).
文摘BACKGROUND:Although the use of non-heart beating donors(NHBDs)could bridge the widening gap between organ demand and supply,its application to liver transplantation is limited due to the high incidence of primary graft loss.Prevention of liver injury in NHBDs will benefit the results of transplantation.This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS:One hundred and four Wistar rats were randomly divided into 7 groups:normal control(n=8) controls 1,2 and 3(C1,C2,C3,n=16),and experimenta 1,2 and 3(E1,E2,E3,n=16).For groups C1 and E1,C2 and E2,and C3 and E3,the warm ischemia time was 0,30,and 45 minutes,respectively.Liver grafts were flushed with and preserved in 4℃Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group Recipients of each experimental group were injected with L-arginine(10 mg/kg body weight)by tail vein 10 minutes before portal vein reperfusion.Donors and recipients of each experimental control group were treated with norma saline.Then transplantation was performed.At 1,3,and 24 hours after portal vein reperfusion,blood samples were obtained to determine the levels of alanine aminotransferase (ALT),aspartate aminotransferase(AST),nitric oxide (NO)and plasma endothelin(ET).At 3 hours after porta vein reperfusion,grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation.RESULTS:At 1 hour after portal vein reperfusion,the levels of NO in groups E1,E2,E3 and C1,C2,C3 were lower,while the levels of plasma ET,serum ALT and AST were higher than those in the normal control group(P<0.05).At 1,3,and 24 hours,the levels of NO in groups E1,E2,E3 were higher,while the levels of plasma ET,serum ALT and AST were lower than those in the corresponding control groups(C1,C2,C3) (P<0.05).The levels of NO in groups C2 and C3 were lower than in group C1(P<0.05),and the level of NO in group C3 was lower than in group C2(P<0.05).At 1,3 and 24 hours, the levels of plasma ET,serum ALT,and AST in groups E1, E2,E3 were lower than those in the corresponding control groups(C1,C2,C3)(P<0.05).The levels of plasma ET,serum ALT,and AST were lower in group C3 than in groups C1 and C2(P<0.05).Pathological changes in groups E1,E2,E3 were milder than those in the corresponding experimental control groups(C1,C2,C3). CONCLUSIONS:The imbalance between NO and ET plays an important role in the development of ischemia- reperfusion injury of liver grafts from NHBDs.L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.
基金This study was supported by National Key R&D Program of China(2017YFD0500500)the earmarked fund for Modern Agro-industry Technology Research System(CARS-40-K12)+1 种基金Beijing Innovation Consortium of Agriculture Research System(BAIC04–2018)the Agricultural Science and Technology Innovation Program(ASTIP)of the Chinese Academy of Agricultural Sciences.
文摘Background:Prenatal nutrition is crucial for embryonic development and neonatal growth,and has the potential to be a main determinant of life-long health.In the present study,we used a layer chick model to investigate the effects of in ovo feeding(IOF)of L-arginine(Arg)on growth,intestinal development,intestinal microbiota and metabolism.The treatments included the non-injected control,saline-injected control,and saline containing 2,6,or 10 mg Arg groups.Results:IOF Arg increased early intestinal index and villus height,and enhanced uptake of residual yolk lipid,contributing to subsequent improvement in the early growth performance of chicks.Prenatal Arg supplementation also increased the early microbialα-diversity,the relative abundance of Lactobacillales and Clostridiales,and decreased the relative abundance of Proteobacteria of cecum in chicks.Furthermore,the shift of cecal microbiota composition and the colonization of potential probiotics were accelerated by IOF of Arg.Simultaneously,metabolomics showed that metabolisms of galactose,taurine-conjugated bile acids and lipids were modulated to direct more energy and nutrients towards rapid growth of intestine at the beginning of post-hatch when embryos received IOF of Arg.Conclusions:Prenatal Arg supplementation showed beneficial effects on the early intestinal development,cecal microbiota and host metabolism of layer chicks,contributing to subsequent improvement in the early growth performance.These findings provide new insight into the role of IOF of Arg in the establishment of the gut microbiota of newly-hatched layer chicks,and can expand our fundamental knowledge about prenatal nutrition,early bacterial colonization and intestinal development in neonate.
基金This study was supported by a grant from foundation of Liaoning ProvincialKey Projects ( No. 0025001 ), China.
文摘BACKGROUND: Post-transplantation pancreatitis andgraft thrombosis are two major complications of pancreastrans-plantation that contribute to morbidity, mortality, andgraft loss. Nitric oxide (NO) is a potent vasodilator agentformed when L-arginine ( L-Arg) is converted to L-citrul-line by the action of NO synthase (NOS), and plays a ma-jor role in microcirculatory changes. We therefore investi-gated the effect of L-Arg on reperfusion injury followingpancreaticoduodenal transplantation in rats.METHODS: The homologous male Wistar rat model ofheterotopic total pancreaticoduodenal transplantation wasused. The L-Arg-treated rats received the intravenous in-jection of L-Arg 5 minutes before and after reperfusion at adose of 200 mg/kg while the N-Nitro-L-arginine methyl es-ter (L-NAME) -treated rats at a dose of 10 mg/kg. Theamount of NO in the pancreas graft was measured. Serumconcentration of cytokine-induced neutrophil chemoattrac-tant ( CINC) was determined by enzyme-linked immu-nosorbant assay, the expression of CINC mRNA was detect-ed by Northern blot assay in the pancreas graft, and the ac-tivity of myeloperoxidase (MPO) was measured. Histolo-gical examination was performed.RESULTS: The amount of NO was higher in the L-Arggroup than in the control group, while it was lower in theL-NAME group than in the control group (P <0.05). Thepeak of serum CINC concentration occurred 3 hours afterreperfusion with the difference among the groups being sig-nificant. The expression peak of CINC mRNA in the pan-creas graft occurred 3 hours after reperfusion. The expres-sion level in the L-Arg group (7.66 ± 1.53 μg/L) was lowerthan in the control group (26.31±2.01 μg/L), while in theL-NAME group (34.18 ±3.12 μg/L) it was higher than thatin the control group (P <0. 05). The activity of MPO inthe L-Arg group was obviously decreasd as compared within the other groups. The pancreas inflammation was ame-liorated when L-Arg was administered, whereas the panc-reas damage was aggravated when L-NAME was adminis-tered.CONCLUSIONS: L-Arg can increase the amount of NOand inhibit the elevation of CINC, the CINC mRNA ex-pression and early neutrophil accumulation in the pancreas.NO has protective effects on ischemia/reperfusion injury inpancreaticoduodenal transplantation.
基金Supported by the National Natural Science Foundation of China (No. 31625025, 31572410, 31572412, 31272450, 31272451)the “111” Project (B16044)。
文摘Background: Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposition in high fat diet-fed Nile tilapia(Oreochromis niloticus).Results: In the present study, we found that dietary supplementation with 1% or 2% arginine decreased the deposition and concentration of fats in the liver;the concentrations of triglycerides, low-density lipoprotein, total cholesterol, and high-density lipoprotein in the serum;and the diameter of adipocytes in intraperitoneal adipose tissue. Compared with the un-supplementation control group, the hepatic activities of alanine aminotransferase,aspartate aminotransferase, and lactate dehydrogenase, and hepatic concentration of malondialdehyde were reduced but these for catalase and superoxide dismutase were enhanced by dietary supplementation with 2% arginine. Arginine supplementation reduced the total amounts of monounsaturated fatty acids, while increasing the total amounts of n-3 and n-6 polyunsaturated fatty acids in the liver. These effects of arginine were associated with reductions in mRNA levels for genes related to lipogenesis(sterol regulatory element-binding protein-1, acetyl-CoA carboxylase α, stearoyl-CoA desaturase, and fatty acid synthase) but increases in mRNA levels for genes involved in fatty acid β-oxidation(carnitine palmitoyltransferase 1α and peroxisome proliferator-activated receptor α). In addition, hepatic mRNA levels for Δ4 fatty acyl desaturase 2 and elongase 5 of very long-chain fatty acids were enhanced by arginine supplementation.Conclusion: These results revealed that dietary L-arginine supplementation to tilapia reduced high fat diet-induced fat deposition and fatty acid composition in the liver by regulating the expression of genes for lipid metabolism.
基金The Finnish Cultural Foundation and The Emil Aaltonen Foundation for the financial support.
文摘In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was developed.As such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis.Various processing methods were used to manufacture highdose formulation batches consisting various amounts of ARG and excipients.The formulations were evaluated using several analytical methods to assess suitability for further investigation.Several batches had enhanced in vitro aerolization properties.Significant future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs.
文摘AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system involvement.METHODS Male Wistar rats underwent superior anterior pancreaticoduodenal vein(SAPDV)-ligation and were treated with a bath at the ligated SAPDV site(BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 m L bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation(filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein(IAPDV) and superior mesenteric vein(SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO-and oxidative stress [malondialdehyde(MDA)]-levels in duodenum.RESULTS Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues.CONCLUSION BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, aneffect related to the NO system and reduction of free radical formation.
文摘AIM To study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide(NO) system agents.METHODS Alongside with the agents' application(after 1 min, medication(/kg, 10 ml/2 min bath/rat) includes: BPC 157(10 μg), L-NAME(5 mg), L-arginine(100mg) alone or combined, and saline baths(controls)) on the rat perforate cecum injury, we continuously assessed the gross reappearance of the vessels(USB microcamera) quickly propagating toward the defect at the cecum surface, defect contraction, bleeding attenuation, MDA-and NO-levels in cecum tissue at 15 min, and severity of cecum lesions and adhesions at 1 and 7 d. RESULTS Post-injury, during/after a saline bath, the number of vessels was significantly reduced, the defect was slightly narrowed, bleeding was significant and MDA-levels increased and NO-levels decreased. BPC 157 bath: the vessel presentation was markedly increased, the defect was noticeably narrowed, the bleeding time was shortened and MDA-and NO-levels remained normal. L-NAME: reduced vessel presentation but not more than the control, did not change defect and shortened bleeding. L-arginine: exhibited less vessel reduction, did not change the defect and prolonged bleeding. In combination, mutual counteraction occurred(L-NAME + L-arginine) or the presentation was similar to that of BPC 157 rats(BPC 157 + L-NAME; BPC 157 + L-arginine; BPC 157 + L-NAME + L-arginine), except the defect did not change. Thereby at day 1 and 7, saline, L-NAME, L-arginine and L-NAME + L-arginine failed(defect was still open and large adhesions present). CONCLUSION The therapeutic effect was achieved with BPC 157 alone or in combination with L-NAME and L-arginine as it was able to consolidate the stimulating and inhibiting effects of the NO-system towards more effective healing recruiting vessels.
文摘A 2 × 2 factorial arrangement was designed to test effects of supplementation of a low (L, 75 mg/kg BW) vs. high (H, 150 mg/kg BW) L-arginine given at early (first 56 days) vs. late (last 56 days) pregnancy on maternal hormones and neonatal traits. Thirty Najdi pregnant ewes were randomly allocated into 6 groups. Ewes in G1 and G2 served as controls (C), given 50 ml saline at either early (CE) or late (CL) pregnancy, respectively. G3 and G4 ewes in early pregnancy received low (LE) and high L-arginine (HE), respectively. G5 and G6 ewes in late pregnancy received low (LL) and high (HL) L-arginine, respectively. A weekly blood sample was collected from initiation of the treatment till parturition. Serum growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin, progesterone (P4) and estradiol 17 β (E2) profiles were determined. Neonatal traits were also determined. Insulin was higher (P 0.05). Lamb survival rates at birth in LE ewes were highest (100%) compared to other treatments. In conclusion, supplementing pregnant ewes with low dosage of L-arginine at early stage of gestation increased lamb birth weight and survival, and improved maternal health.
基金Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil
文摘AIM: To study the benef icial effects of triterpene α,β-amyrin and the underlying mechanisms in an experimental pancreatitis model. METHODS: Acute pancreatitis was induced in five groups of rats (n = 8) by L-arginine (2 × 2.5 g/kg, intraperitoneal, 1 h apart) and 1 h later, they received a single oral dose of α,β-amyrin (10, 30 and 100 mg/kg),methylprednisolone (30 mg/kg) and vehicle (3% Tween 80). A saline (0.9% NaCl) treated group served as a normal control. Efficacy was assessed at 24 h by determination of serum levels of amylase, lipase and proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-6], pancreatic myeloperoxidase (MPO) activity, lipid peroxidation [thiobarbituric acid reactive substances (TBARS)], nitrate/nitrite levels, and the wet weight/body weight ratio. Tissue histology and the immunoreactivity for TNF-α and inducible nitric oxide synthetase (iNOS) were performed. RESULTS: α,β-amyrin and methylprednisolone treatments significantly (P < 0.05) attenuated the L-arginine-induced increases in pancreatic wet weight/body weight ratio, and decreased the serum levels of amylase and lipase, and TNF-α and IL-6, as compared to the vehicle control. Also, pancreatic levels of MPO activity, TBARS, and nitrate/nitrite were signifi cantly lower. Histological f indings and TNF-α and iNOS immunostaining further confirmed the amelioration of pancreatic injury by α,β-amyrin. CONCLUSION: α,β-amyrin has the potential to combat acute pancreatitis by acting as an anti-in? ammatory and antioxidant agent.
文摘Hepatic injury can be induced by the administration of carbon tetrachloride (CCl4) via the production of free radicals. The present work was initiated to investigate the kidney response to hepatic injury induced by CCl4 and its treatment by L-arginine. Female Swiss albino mice were supplied with L-arginine for 6 days (orally, 200 mg/kg body weight) prior or post to hepatic injury induction through i.p. injection with a single dose of CCl4 (20 mg/kg body weight) for 24 h. After hepatic injury induction, renal MDA content was significantly elevated while renal GSH level and the activities of antioxidant enzymes (GR, GPx, GST, catalase, and SOD) were significantly decreased. These results suggest that CCl4 not only induces hepatic injury but also induces kidney dysfunction side by side. Following the treatment with L-arginine, all levels were almost back to normal. Therefore, Larginine administration is found to be an effective protector of both liver and kidney against CCl4-intoxication.
基金This project was supported by the Natural Science Foundation of China
文摘The heavy lanthanide ions（Dy,Ho,Er,Tm and Yb）were used to probe the conformation of L-arginine inaqueous solution.The results showed that the contact contribution to the observed<sup>13</sup>C paramagnetic shift is verysmall for nuclei four or more bonds away from the bound lanthanide ion and it is significant for those in closeproximity to the lanthanide ion.The overall conformation of L-arginine was established by fitting the calculatedgeometric factors for the corresponding experimental data.In the lanthanide-L-arginine complex,the wholebackbone of the ligand is located outsite the zero-dipolar shift cone of the lanthanide ion with the carboxyl groupselectively coordinated to the metal.The calculated RE-O distance is 0.21 nm for the bidentate coordinationmode and the ligand is in an extended conformation in the solution with the molecular backbone corresponding tothe trans form.
文摘BACKGROUND: There is much debate over the regulation of mitochondrial calcium overload and reducing the impairment of energy metabolism in hepatic cells. It has not been reported whether L-arginine (L-Arg) can affect hepatic mitochondrial calcium overload. This study was undertaken to investigate the protective effect of L-Arg on Ca2+ handling of hepatic mitochondrion in rats with obstructive jaundice and to clarify its possible mechanism. METHODS: Seventy-two male SD rats were randomly divided into 3 groups: sham operation+normal saline group (SO group), common bile duct ligation+normal saline group (BDL group), and common bile duct ligation+ L-Arg group (L-Arg group). The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and Ca2+ in rat hepatic mitochondrion were examined at the 7th, 14th and 21st day after operation. RESULTS: The Ca2+ and MDA levels of hepatic mitochondrion increased significantly but their SOD content decreased markedly at each time point in the BDL group. Except at the 21st day, the Ca2+ and MDA, contents of hepatic mitochondrion were significantly lower, and SOD concentrations were higher in the L-Arg group than those in the BDL group at the 7th and 14th day (P【0.01). CONCLUSION: L-Arg has a protective effect on mitochondrion in the early and mid stages of obstructive jaundice.
基金financially supported by the National Natural Science Foundation of China(81673384)。
文摘Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics.The newly emerging role of nitric oxide(NO)to conquer drug resistance has been recognized as a potential strategy.However,it remains a great challenge to realize targeted delivery as well as accurate release of NO at desired sites.Herein,we developed a PEGylated indocyanine green(m PEG-ICG)integrated nanovesicle system(PIDA)to simultaneously load doxorubicin hydrochloride(DOX·HCl)and the NO donor L-arginine(L-Arg),which can produce NO triggered by NIR light irradiation and exert multimodal therapy to sensitize drug-resistant cancers.Upon 808 nm irradiation,the NO released from PIDA led to a decrease in mitochondrial membrane potential,an increase in ROS and significant ATP depletion in K562/ADR cells,thus inhibiting cell growth and resolving the problem of drug resistance.Consequently,the in vivo experiment on K562/ADR-bearing nude mice indicated that PIDA nanovesicles achieved significant anticancer efficacy with a tumor inhibition rate of 80.8%.Above all,PIDA nanovesicles offer guidance for designing nanoplatforms for drug-resistant cancer treatment.
文摘Objective:To evaluate the levels of estrogen,albumin and gonadotropins(luteinizing hormone,follicle-stimulating hormone)as well as the activity of dopamine beta hydroxylase(DAβH)in aged female rats treated with nitric oxide precursor L-arginine and neuronal nitric oxide synthase antagonist L-NAME.Methods:A total of 224 Wistar rats(36 weeks old,weighing 250 g)based on a random sampling were divided into the control and experimental groups after Pap smear test.The control group received only saline(1 mL/kg)intraperitoneally(i.p.).The experiential groups were treated with L-arginine(5,25 and 50 mg/kg,i.p.)and L-NAME(5 and 25 mg/kg,i.p.)for 3 to 21 days,once a day.Blood samples were taken from the rats and the levels of estrogen and albumin and gonadotropins in the serum were monitored by enzyme-linked immunosorbent assay kit,and the ovaries were examined immunohistopathologically for DAβH activity.Results:L-arginine(5 mg/kg)significantly increased estrogen level(P<0.05),which was associated with DAβH activation in the ovaries.L-NAME reduced this effect when administered prior to L-arginine dose.L-arginine caused no significant change in the levels of luteinizing hormone and follicle-stimulating hormone.Except for the lowest dose of L-arginine in the shortest period,albumin levels significantly decreased in other treatments compared to the control group(P<0.05).Conclusions:L-arginine is likely to reduce postmenopausal problems due to an increased nitric oxide level.
