AIM: To investigate the effect of aminoguanidine(AG) on the expression of caspase-3 in rat retina after ischemiareperfusion injury.METHODS: The rats were anesthetized with 30mg/kg sodium pentobarbital introperitoneal(...AIM: To investigate the effect of aminoguanidine(AG) on the expression of caspase-3 in rat retina after ischemiareperfusion injury.METHODS: The rats were anesthetized with 30mg/kg sodium pentobarbital introperitoneal(ip) injections.After topical application of 10g/L dicaine,the anterior chamber was punctured with a 5-gauge needle connected to a bottle containing normal saline.Intraocular pressure was raised to 100 mmHg by elevating the saline container.The infusion needle was removed from the anterior chamber 60 minutes later.Reperfusion of the retinal vasculature was confirmed by fundus examination.AG 100mg/kg was ip injected in drug group.The rats were then euthanatized at 6,24,and 72 hours after reperfusion,and their eyes were enucleated for immunohistochemistry.RESULTS: No specific staining was detected by using the caspase-3 antibody in the retina of control group.In ischemia group,the protein of caspase-3 was over-expressed at 6 hours and relieved at 24 hours and 72 hours,while with drug treatment,the expression of protein of caspase-3 was decreased at each time point.CONCLUSION: AG provides retinal protection against ischemia-reperfusion injury in rat retina,probably through an inducible NOS-dependent mechanism.展开更多
AIM:To explore the protective effects of amino-guanidine(AG) on retinal apoptosis in mice with oxygeninduced retinopathy(OIR).·METHODS:A total of 80 C57BL/6J mice,aged 7 days,were randomly divided into four group...AIM:To explore the protective effects of amino-guanidine(AG) on retinal apoptosis in mice with oxygeninduced retinopathy(OIR).·METHODS:A total of 80 C57BL/6J mice,aged 7 days,were randomly divided into four groups:normal,high oxygen,high oxygen saline and high oxygen treated with AG.In the normal group,mice were housed in normoxic conditions from postnatal day P7 to P17.Mice in the other 3 groups were placed under hyperoxic conditions(75 ±2% O2) in an oxygen-regulated chamber for 5 days and subsequently placed in normoxic conditions for 5days.Mice in the AG group were treated once daily,from P12 to P17,with AG hemisulfate(100mg/kg body weight,intraperitoneally) dissolved in physiological saline.An equivalent amount of 0.9% physiological saline was administered,as above,to mice in the high oxygen saline group.Ten mice were randomly selected from each group on P14 and on P17,euthanized and the retinas examined.Apoptotic cells in the retina were detected using the terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) method.The expression of nitric oxide synthase(iNOS) in the retina was detected by immunohistochemistry and changes in rod cells were observed using electron microscopy.·RESULTS:TUNEL-positive cells and iNOS immunoreactive neurons were present in the inner nuclear and ganglion cell retinal layers of mice in the high oxygen group.The number of TUNEL-positive cells was significantly greater in the high oxygen group compared with the normal group(t =-20.81,P14d<0.05;t =-15.05,P17d<0.05).However,the number of TUNEL-positive cells in the AG treatment group was significantly lower(t =-13.21,P14d<0.05;t =-6.61,P17d<0.05) compared with thehigh oxygen group.The expression of iNOS was significantly higher in the high oxygen group compared with the normal group(t =-21.95,P14d<0.05;t =-17.30,P17d<0.05).However,the expression of iNOS in the AG treatment group was significantly lower(t =-12.17,P14d<0.05;t =-10.30,P17d<0.05) compared with the high oxygen group.The outer segments of the rods were disorganized and short in the high oxygen group.Rod morphology appeared to be slightly improved in the AG group.·CONCLUSION:AG may protect retinal neurons in OIR by inhibiting apoptosis.The mechanism may be related to iNOS.展开更多
The present study aimed at investigating physicochemical changes in modified LDL by sugars specifically fructose due to recent reports on its involvement in cardiovascular diseases and also glucose and their role in s...The present study aimed at investigating physicochemical changes in modified LDL by sugars specifically fructose due to recent reports on its involvement in cardiovascular diseases and also glucose and their role in subsequent in vitro accumulation of cholesterol in macrophages. Antiglycation action of aminoguanidine was also investigated. LDL isolated from human blood was incubated with fructose or glucose and aminoguanidine where indicated. The physicochemical changes in modified LDL were detected by electrophoretic, spectroscopic and chemical analysis. Accumulation of cholesterol and its inhibiton in human monocyte-derived macrophages incubated with modified LDL was determined by HPLC. Results showed increased relative electrophoretic mobility, hyperchromicity at 280 nm, development of AGE fluorescence, decrease in free amino groups and increased carbonyl content in glycated LDL as compared to native LDL. Also total cholesterol accumulated in macrophages was more for glycated LDL as compared to native LDL. The magnitude of changes was more prominent in case of fructose as compared to glucose. Aminoguanidine showed remarkable restriction of glycation-induced alterations in LDL and also in accumulation of cholesterol in macrophages. The study thus proclaims that LDL-AGEs formed by fructose may contribute to accelerated initiation of diabetes induced atherosclerosis via foam cells generation and aminoguanidine may have therapeutic potential against it.展开更多
Aminoguanidine hydrazones (AGHs) are a class of compounds that have interesting pharmacological activities. They are derived from the same chemical group as aminoguanidine, so it has mixed properties (receptor and don...Aminoguanidine hydrazones (AGHs) are a class of compounds that have interesting pharmacological activities. They are derived from the same chemical group as aminoguanidine, so it has mixed properties (receptor and donor) in the formation of hydrogen bonds. Its anticancer agent properties were recently highlighted, but the molecules of this class have solubility in aqueous solutions that can be considered low. The identification of this class, by a simple, sensitive and low-cost technique, such as electrochemistry, which also allows the evaluation of its solubilization process through agents such as PAMAM dendrimer is the main objective of the work described here. The electrochemical response of the LQM10 (AGH derivative) was evaluated, as well as its behavior in different electrochemical sensors. Electrochemical experiments were performed in buffered (phosphate at pH 7.02 and acetate at 4.5). LQM10 has a reversible oxidation peak with a potential of +0.22 V. It was efficiently detected in different electrodes tested (glass carbon/CNT, glass carbon/CNT/PAMAM), which proves the viability of the electrodes for various analyses and has the determination of the apparent constant association, indicating its interaction with the analysis that is higher in the presence of the PAMAM encapsulating agent. This was corroborated by the results for the modified gold electrode with MUA and PAMAM. The sum of the results shows the possibility of electrochemically evaluating the Aminoguanidine hydrazone derivative, the viability of electrodes employed and the greater solubilization of LQM10 in the presence of the PAMAM dendrimer.展开更多
AIM:To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation,apoptosis,redox status and vascularization.METHODS:Xenografts of PANC-1 cells were developed in nude mice. Th...AIM:To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation,apoptosis,redox status and vascularization.METHODS:Xenografts of PANC-1 cells were developed in nude mice. The animals were separated into two groups:control and aminoguanidine treated. Tumor growth,survival and appearance of metastases were determined in vivo in both groups. Tumors were excised and ex vivo histochemical studies were performed. Cell growth was assessed by Ki-67 expression. Apoptosis was studied by intratumoral expression of B cell lymphoma-2 protein (Bcl-2) family proteins and Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (Tunel). Redox status was evaluated by the expression of endothelial nitric oxide synthase (eNOS),catalase,copper-zinc superoxide dismutase (CuZnSOD),manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx). Finally,vascularization was determined by Massons trichromic staining,and by VEGF and CD34 expression.RESULTS:Tumor volumes after 32 d of treatment by aminoguanidine (AG) were significantly lower than in control mice (P < 0.01). Median survival of AG mice was significantly greater than control animals (P < 0.01). The appearance of both homolateral and contralateral palpable metastases was significantly delayed in AG group. Apoptotic cells,intratumoral vascularization (trichromic stain) and the expression of Ki-67,Bax,eNOS,CD34,VEGF,catalase,CuZnSOD and MnSOD were diminished in AG treated mice (P < 0.01),while the expression of Bcl-2 and GPx did not change.CONCLUSION:The antitumoral action of aminoguanidine is associated with decreased cell proliferation,reduced angiogenesis,and reduced expression of antioxidant enzymes.展开更多
The single crystal of aminoguanidine sulfate monohydrate [(AG)2SO4·H2O] is obtained and its structure is determined by X-ray diffraction analysis. The compound crystallizes in orthorhombic system with space group...The single crystal of aminoguanidine sulfate monohydrate [(AG)2SO4·H2O] is obtained and its structure is determined by X-ray diffraction analysis. The compound crystallizes in orthorhombic system with space group Pnma and the empirical formula C2H 16N8O5S. The unit cell parameters are as follows: a= 0.6759(2)nm, b=1.4131(5)nm, c=1.1650(4)nm, V=1.1128(6)nm3, Z=4, Dc= 1.578g/cm3, F(000)=560, s=1.069, μ(MoKα)=0.318mm -1. The final R and wR are 0.0312 and 0.0833, respectively. The title compound is an ionic compound and its structure unit consists of two aminoguanidium cations, one sulfate anion and one crystal water molecule, which are interconnected by electrostatic forces and hydrogen bonds into net structure, making the title compound very stable. Under a linear heating rate, the thermal decomposition processes of (AG)2SO4·H2O have one endothermal dehydration stage, one melting process and one exothermic decomposition stage at 50-400℃, and can evolve abundant gas products.展开更多
Background The accumulation of free radicals and advanced glycation end products(AGEs)in cell plays a veryimportant role in replicative senescence.Aminoguanidine(AG)has potential antioxidant effects and decreases AGEl...Background The accumulation of free radicals and advanced glycation end products(AGEs)in cell plays a veryimportant role in replicative senescence.Aminoguanidine(AG)has potential antioxidant effects and decreases AGElevels.This study aimed to investigate its effect on replicative senescence in vitro.Methods The effects of aminoguanidine on morphology,replicative lifespan,cell growth and proliferation,AGEs,DNAdamage,DNA repair ability and telomere length were observed in human fetal lung diploid fibroblasts(2BS).Results Aminoguanidine maintained the non-senescent phenotype of 2BS cells even at late population doubling(PD)and increased cumulative population doublings by at least 17-21 PDs.Aminoguanidine also improved the potentials ofgrowth and proliferation of 2BS cells as detected by the MTT assay.The AGE levels of late PD cells grown from early PDin DMEM containing aminiguanidine decreased significantly compared with those of late PD control cells and were similarto those of young control cells.In addition,the cells pretreated with aminoguanidine had a significant reduction in DNAstrand breaks when they were exposed to 200 μmol/L H_2O_2 for 5 minutes which indicated that the compound had astrong potential to protect genomic DNA against oxidative stress.And most of the cells exposed to 100 μmol/L H_2O_2 hadmuch shorter comet tails and smaller tail areas after incubation with aminoguanidine-supplemented DMEM,whichindicated that the compound strongly improved the DNA repair abilities of 2BS cells.Moreover,PD55 cells grown fromPD28 in 2 mmol/L or 4 mmol/L aminoguanidine retain telomere lengths of 7.94 kb or 8.12 kb,which was 0.83 kb or 1.11kb longer than that of the control cells.Conclusion Aminoguanidine delays replicative senescence of 2BS cells and the senescence-delaying effect ofaminoguanidine appear to be due to its many biological properties including its potential for proliferation improvement,itsinhibitory effect of AGE formation,antioxidant effect,improvement of DNA repair ability and the slowdown of telomereshortening.展开更多
文摘AIM: To investigate the effect of aminoguanidine(AG) on the expression of caspase-3 in rat retina after ischemiareperfusion injury.METHODS: The rats were anesthetized with 30mg/kg sodium pentobarbital introperitoneal(ip) injections.After topical application of 10g/L dicaine,the anterior chamber was punctured with a 5-gauge needle connected to a bottle containing normal saline.Intraocular pressure was raised to 100 mmHg by elevating the saline container.The infusion needle was removed from the anterior chamber 60 minutes later.Reperfusion of the retinal vasculature was confirmed by fundus examination.AG 100mg/kg was ip injected in drug group.The rats were then euthanatized at 6,24,and 72 hours after reperfusion,and their eyes were enucleated for immunohistochemistry.RESULTS: No specific staining was detected by using the caspase-3 antibody in the retina of control group.In ischemia group,the protein of caspase-3 was over-expressed at 6 hours and relieved at 24 hours and 72 hours,while with drug treatment,the expression of protein of caspase-3 was decreased at each time point.CONCLUSION: AG provides retinal protection against ischemia-reperfusion injury in rat retina,probably through an inducible NOS-dependent mechanism.
文摘AIM:To explore the protective effects of amino-guanidine(AG) on retinal apoptosis in mice with oxygeninduced retinopathy(OIR).·METHODS:A total of 80 C57BL/6J mice,aged 7 days,were randomly divided into four groups:normal,high oxygen,high oxygen saline and high oxygen treated with AG.In the normal group,mice were housed in normoxic conditions from postnatal day P7 to P17.Mice in the other 3 groups were placed under hyperoxic conditions(75 ±2% O2) in an oxygen-regulated chamber for 5 days and subsequently placed in normoxic conditions for 5days.Mice in the AG group were treated once daily,from P12 to P17,with AG hemisulfate(100mg/kg body weight,intraperitoneally) dissolved in physiological saline.An equivalent amount of 0.9% physiological saline was administered,as above,to mice in the high oxygen saline group.Ten mice were randomly selected from each group on P14 and on P17,euthanized and the retinas examined.Apoptotic cells in the retina were detected using the terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) method.The expression of nitric oxide synthase(iNOS) in the retina was detected by immunohistochemistry and changes in rod cells were observed using electron microscopy.·RESULTS:TUNEL-positive cells and iNOS immunoreactive neurons were present in the inner nuclear and ganglion cell retinal layers of mice in the high oxygen group.The number of TUNEL-positive cells was significantly greater in the high oxygen group compared with the normal group(t =-20.81,P14d<0.05;t =-15.05,P17d<0.05).However,the number of TUNEL-positive cells in the AG treatment group was significantly lower(t =-13.21,P14d<0.05;t =-6.61,P17d<0.05) compared with thehigh oxygen group.The expression of iNOS was significantly higher in the high oxygen group compared with the normal group(t =-21.95,P14d<0.05;t =-17.30,P17d<0.05).However,the expression of iNOS in the AG treatment group was significantly lower(t =-12.17,P14d<0.05;t =-10.30,P17d<0.05) compared with the high oxygen group.The outer segments of the rods were disorganized and short in the high oxygen group.Rod morphology appeared to be slightly improved in the AG group.·CONCLUSION:AG may protect retinal neurons in OIR by inhibiting apoptosis.The mechanism may be related to iNOS.
文摘The present study aimed at investigating physicochemical changes in modified LDL by sugars specifically fructose due to recent reports on its involvement in cardiovascular diseases and also glucose and their role in subsequent in vitro accumulation of cholesterol in macrophages. Antiglycation action of aminoguanidine was also investigated. LDL isolated from human blood was incubated with fructose or glucose and aminoguanidine where indicated. The physicochemical changes in modified LDL were detected by electrophoretic, spectroscopic and chemical analysis. Accumulation of cholesterol and its inhibiton in human monocyte-derived macrophages incubated with modified LDL was determined by HPLC. Results showed increased relative electrophoretic mobility, hyperchromicity at 280 nm, development of AGE fluorescence, decrease in free amino groups and increased carbonyl content in glycated LDL as compared to native LDL. Also total cholesterol accumulated in macrophages was more for glycated LDL as compared to native LDL. The magnitude of changes was more prominent in case of fructose as compared to glucose. Aminoguanidine showed remarkable restriction of glycation-induced alterations in LDL and also in accumulation of cholesterol in macrophages. The study thus proclaims that LDL-AGEs formed by fructose may contribute to accelerated initiation of diabetes induced atherosclerosis via foam cells generation and aminoguanidine may have therapeutic potential against it.
基金Brazilian agencies CNPq,CAPES,FAPEAL and UFAL for financial support
文摘Aminoguanidine hydrazones (AGHs) are a class of compounds that have interesting pharmacological activities. They are derived from the same chemical group as aminoguanidine, so it has mixed properties (receptor and donor) in the formation of hydrogen bonds. Its anticancer agent properties were recently highlighted, but the molecules of this class have solubility in aqueous solutions that can be considered low. The identification of this class, by a simple, sensitive and low-cost technique, such as electrochemistry, which also allows the evaluation of its solubilization process through agents such as PAMAM dendrimer is the main objective of the work described here. The electrochemical response of the LQM10 (AGH derivative) was evaluated, as well as its behavior in different electrochemical sensors. Electrochemical experiments were performed in buffered (phosphate at pH 7.02 and acetate at 4.5). LQM10 has a reversible oxidation peak with a potential of +0.22 V. It was efficiently detected in different electrodes tested (glass carbon/CNT, glass carbon/CNT/PAMAM), which proves the viability of the electrodes for various analyses and has the determination of the apparent constant association, indicating its interaction with the analysis that is higher in the presence of the PAMAM encapsulating agent. This was corroborated by the results for the modified gold electrode with MUA and PAMAM. The sum of the results shows the possibility of electrochemically evaluating the Aminoguanidine hydrazone derivative, the viability of electrodes employed and the greater solubilization of LQM10 in the presence of the PAMAM dendrimer.
基金Supported by Grants from University of Buenos Aires (B098 and B112)
文摘AIM:To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation,apoptosis,redox status and vascularization.METHODS:Xenografts of PANC-1 cells were developed in nude mice. The animals were separated into two groups:control and aminoguanidine treated. Tumor growth,survival and appearance of metastases were determined in vivo in both groups. Tumors were excised and ex vivo histochemical studies were performed. Cell growth was assessed by Ki-67 expression. Apoptosis was studied by intratumoral expression of B cell lymphoma-2 protein (Bcl-2) family proteins and Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (Tunel). Redox status was evaluated by the expression of endothelial nitric oxide synthase (eNOS),catalase,copper-zinc superoxide dismutase (CuZnSOD),manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx). Finally,vascularization was determined by Massons trichromic staining,and by VEGF and CD34 expression.RESULTS:Tumor volumes after 32 d of treatment by aminoguanidine (AG) were significantly lower than in control mice (P < 0.01). Median survival of AG mice was significantly greater than control animals (P < 0.01). The appearance of both homolateral and contralateral palpable metastases was significantly delayed in AG group. Apoptotic cells,intratumoral vascularization (trichromic stain) and the expression of Ki-67,Bax,eNOS,CD34,VEGF,catalase,CuZnSOD and MnSOD were diminished in AG treated mice (P < 0.01),while the expression of Bcl-2 and GPx did not change.CONCLUSION:The antitumoral action of aminoguanidine is associated with decreased cell proliferation,reduced angiogenesis,and reduced expression of antioxidant enzymes.
基金the National Natural Science Foundation of China(20471008) the Basic Research Foundation of Beijing Institute of Technology(200302B01)
文摘The single crystal of aminoguanidine sulfate monohydrate [(AG)2SO4·H2O] is obtained and its structure is determined by X-ray diffraction analysis. The compound crystallizes in orthorhombic system with space group Pnma and the empirical formula C2H 16N8O5S. The unit cell parameters are as follows: a= 0.6759(2)nm, b=1.4131(5)nm, c=1.1650(4)nm, V=1.1128(6)nm3, Z=4, Dc= 1.578g/cm3, F(000)=560, s=1.069, μ(MoKα)=0.318mm -1. The final R and wR are 0.0312 and 0.0833, respectively. The title compound is an ionic compound and its structure unit consists of two aminoguanidium cations, one sulfate anion and one crystal water molecule, which are interconnected by electrostatic forces and hydrogen bonds into net structure, making the title compound very stable. Under a linear heating rate, the thermal decomposition processes of (AG)2SO4·H2O have one endothermal dehydration stage, one melting process and one exothermic decomposition stage at 50-400℃, and can evolve abundant gas products.
基金This work was supported by the grants from the National Natural Science Foundation of China(No.30672469)the Beijing Natural Science Foundation(No.7062030)
文摘Background The accumulation of free radicals and advanced glycation end products(AGEs)in cell plays a veryimportant role in replicative senescence.Aminoguanidine(AG)has potential antioxidant effects and decreases AGElevels.This study aimed to investigate its effect on replicative senescence in vitro.Methods The effects of aminoguanidine on morphology,replicative lifespan,cell growth and proliferation,AGEs,DNAdamage,DNA repair ability and telomere length were observed in human fetal lung diploid fibroblasts(2BS).Results Aminoguanidine maintained the non-senescent phenotype of 2BS cells even at late population doubling(PD)and increased cumulative population doublings by at least 17-21 PDs.Aminoguanidine also improved the potentials ofgrowth and proliferation of 2BS cells as detected by the MTT assay.The AGE levels of late PD cells grown from early PDin DMEM containing aminiguanidine decreased significantly compared with those of late PD control cells and were similarto those of young control cells.In addition,the cells pretreated with aminoguanidine had a significant reduction in DNAstrand breaks when they were exposed to 200 μmol/L H_2O_2 for 5 minutes which indicated that the compound had astrong potential to protect genomic DNA against oxidative stress.And most of the cells exposed to 100 μmol/L H_2O_2 hadmuch shorter comet tails and smaller tail areas after incubation with aminoguanidine-supplemented DMEM,whichindicated that the compound strongly improved the DNA repair abilities of 2BS cells.Moreover,PD55 cells grown fromPD28 in 2 mmol/L or 4 mmol/L aminoguanidine retain telomere lengths of 7.94 kb or 8.12 kb,which was 0.83 kb or 1.11kb longer than that of the control cells.Conclusion Aminoguanidine delays replicative senescence of 2BS cells and the senescence-delaying effect ofaminoguanidine appear to be due to its many biological properties including its potential for proliferation improvement,itsinhibitory effect of AGE formation,antioxidant effect,improvement of DNA repair ability and the slowdown of telomereshortening.
