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 Stable microtubules （MTs） is involved the mechanism of diabetic cardiomyopathy （DCM）, which is induced by acetylation of α-tubulin. The present study investigated whether SIRT2, a deacetylase, regulates MT st...Aim Stable microtubules （MTs） is involved the mechanism of diabetic cardiomyopathy （DCM）, which is induced by acetylation of α-tubulin. The present study investigated whether SIRT2, a deacetylase, regulates MT stability through α-tubulin deacetylation in DCM and whether the receptor of advanced glycation end products （AGEs） signaling pathway is involved in this effect. Methods Type 1 diabetic mellitus （T1DM） rats model was established by a single intraperitoneal injection of streptozotocin （STZ, 65 mg · kg^-1） , and neonatal rat cardio- myocytes were also cultured. Heart function was detected by Doppler. MT stability was elevated by β-tubulin ex- pression density. The protein expression of SIRT2, acetylated α-tubulin and AGEs receptor were detected by immu- nohistochemistry or Western blots. The interaction of SIRT2 and acetylated α-tubulin was detected by Co-immuno- precipitation. Results In an animal model of T1DM, Western blot and immunohistochemistry revealed downregu- lation of SIRT2 but upregulation of the acetylated α-tubulin protein. These effects were reduced by treatment of aminoguanidine, an inhibitor of AGEs production. HDAC6 expression did not regulated in heart. In primary cul- tures of neonatal rat cardiomyocytes, the AGEs treatment impaired the SIRT2/acetylated α-tubulin signaling path- way, and SIRT2-overexpression reversed the function of AGEs on cardiomyocytes. In addition, gene silencing of AGEs receptor alleviated the impairment effect of AGEs on cardiomyocytes. Conclusion In conclusion, these data demonstrate that AGEs/AGEs receptor promote MT stabilization via the suppression of the SIRT2/acetylated α-tu- bulin signaling pathway in DCM development.展开更多
Aminoguanidine lanthanide thiodipropionate hydrates of composition [Ln(Agun)2(tdp)3·nH2O], Agun = Aminoguanidine, tdp = thiodipropionic acid, where Ln = La, Pr, Nd and Sm if n = 2, have been prepared and chara...Aminoguanidine lanthanide thiodipropionate hydrates of composition [Ln(Agun)2(tdp)3·nH2O], Agun = Aminoguanidine, tdp = thiodipropionic acid, where Ln = La, Pr, Nd and Sm if n = 2, have been prepared and characterized by physic-chemical techniques.展开更多
Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been sho...Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been shown that statins have antiinflammatory effects independent of their lipid-lowering effects and these anti-inflammatory effects inhibit the inflammation and pain process. This study evaluated the antinociceptive and anti-inflammatory effects of rosuvastatin using the acetic acid writhing, the formalin hind paw, the orofacial formalin and the hot plate tests. The following experimental group were used: control, acute (1 day) and chronic (3 days) after oral gavage with rosuvastatin (3, 10, 30, 100 and 300 mg/kg). Rosuvastatin produced a dose-dependent antinociception, with different potency, in all the tests. Additionally, nitric oxide synthase inhibitors (Abbreviationsand aminoguanidine) were used to assess the nitric oxide participation on this induced rosuvastatin antinociception. The data demonstrated the antinociceptive and anti-inflammatory activity of rosuvastatin in algesiometer models of tonic or phasic pain. These activities seem to be induced by modulation of iNOS expression, a result that may be relevant in the pharmacological treatment of human pain where rosuvastatin and nitric oxide synthase inhibitors must be used.展开更多
To investigate the effect of advanced glycosylation end products (AGEs) on the activity of protein kinase C (PKC) in human peripheral blood mononuclear cells (PBMC) and to observe whether aminoguanidine (AG) can influ...To investigate the effect of advanced glycosylation end products (AGEs) on the activity of protein kinase C (PKC) in human peripheral blood mononuclear cells (PBMC) and to observe whether aminoguanidine (AG) can influence the effect of AGEs Methods After PBMC were isolated from human peripheral blood and incubated with different concentrations of AGEs BSA for various periods, total PKC activity in PBMC was determined by measuring the incorporation of 32 P from [γ 32 P] ATP into a special substrate using Promega PKC assay kit Results AGEs BSA increased the total PKC activity in PBMC from 83 43±6 57?pmol/min/mg protein to 116 8±13 82?pmol/min/mg protein with a peak at 15?min AGEs BSA also increased the total PKC activity in a concentration dependent manner from 83 1±6 4?pmol/min/mg protein (control) to 119 1±13 3?pmol/min/mg protein (control vs AGEs BSA 400?mg/L, P <0 01) Furthermore, AGEs BSA induced an elevation of PKC activity in a glycosylating time related manner, from 80 9±8 2 (control) to 118 3±11 5?pmol/min/mg protein (glycosylation for 12 wk, P <0 01) The total PKC activity stimulated by AGEs BSA pretreated with AG (100, 200?mg/L) was markedly lower than that of AGEs BSA group not pretreated with AG ( P <0 05, P <0 01) Conclusions AGEs BSA increased the total PKC activity in PBMC in a concentration and incubation time dependent manner The ability of AGEs BSA to stimulate PKC activity was markedly decreased by pretreatment of AGEs BSA with展开更多
To study the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on renal alteration in diabetic rats Methods Insulin or aminoguanidine was administered to diab...To study the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on renal alteration in diabetic rats Methods Insulin or aminoguanidine was administered to diabetic rats Blood glucose, hemoglobin A 1C (HbA 1C ), glomerular tissue extracts AGE (GTE AGE), PKC, glomerular basement membrane thickness (GBMT) and urine protein/creatinine (Pr/Cr) ratio in diabetic rats were measured and analysed Results Levels of blood glucose, HbA 1C and AGE, PKC activity, the Pr/Cr ratio and GBMT were all significantly increased ( P values all less than 0 01) in diabetic rats Insulin could decrease the formation of HbA 1C and AGE, and improve PKC activity Aminoguanidine had no influence on PKC activity ( P >0 05) although it decreased the formation of AGE Both drugs could delay the increase of urine Pr/Cr ratio and GBMT ( P <0 05 or P <0 01) Conclusions Chronic hyperglycemia may lead to an increase of PKC activity HbA 1C and AGE may not directly contribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GBM thickening It is important to inhibit the formation of AGE and reduce the PKC activity so as to prevent or delay the development of diabetic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.
文摘Aim Stable microtubules （MTs） is involved the mechanism of diabetic cardiomyopathy （DCM）, which is induced by acetylation of α-tubulin. The present study investigated whether SIRT2, a deacetylase, regulates MT stability through α-tubulin deacetylation in DCM and whether the receptor of advanced glycation end products （AGEs） signaling pathway is involved in this effect. Methods Type 1 diabetic mellitus （T1DM） rats model was established by a single intraperitoneal injection of streptozotocin （STZ, 65 mg · kg^-1） , and neonatal rat cardio- myocytes were also cultured. Heart function was detected by Doppler. MT stability was elevated by β-tubulin ex- pression density. The protein expression of SIRT2, acetylated α-tubulin and AGEs receptor were detected by immu- nohistochemistry or Western blots. The interaction of SIRT2 and acetylated α-tubulin was detected by Co-immuno- precipitation. Results In an animal model of T1DM, Western blot and immunohistochemistry revealed downregu- lation of SIRT2 but upregulation of the acetylated α-tubulin protein. These effects were reduced by treatment of aminoguanidine, an inhibitor of AGEs production. HDAC6 expression did not regulated in heart. In primary cul- tures of neonatal rat cardiomyocytes, the AGEs treatment impaired the SIRT2/acetylated α-tubulin signaling path- way, and SIRT2-overexpression reversed the function of AGEs on cardiomyocytes. In addition, gene silencing of AGEs receptor alleviated the impairment effect of AGEs on cardiomyocytes. Conclusion In conclusion, these data demonstrate that AGEs/AGEs receptor promote MT stabilization via the suppression of the SIRT2/acetylated α-tu- bulin signaling pathway in DCM development.
文摘Aminoguanidine lanthanide thiodipropionate hydrates of composition [Ln(Agun)2(tdp)3·nH2O], Agun = Aminoguanidine, tdp = thiodipropionic acid, where Ln = La, Pr, Nd and Sm if n = 2, have been prepared and characterized by physic-chemical techniques.
文摘Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been shown that statins have antiinflammatory effects independent of their lipid-lowering effects and these anti-inflammatory effects inhibit the inflammation and pain process. This study evaluated the antinociceptive and anti-inflammatory effects of rosuvastatin using the acetic acid writhing, the formalin hind paw, the orofacial formalin and the hot plate tests. The following experimental group were used: control, acute (1 day) and chronic (3 days) after oral gavage with rosuvastatin (3, 10, 30, 100 and 300 mg/kg). Rosuvastatin produced a dose-dependent antinociception, with different potency, in all the tests. Additionally, nitric oxide synthase inhibitors (Abbreviationsand aminoguanidine) were used to assess the nitric oxide participation on this induced rosuvastatin antinociception. The data demonstrated the antinociceptive and anti-inflammatory activity of rosuvastatin in algesiometer models of tonic or phasic pain. These activities seem to be induced by modulation of iNOS expression, a result that may be relevant in the pharmacological treatment of human pain where rosuvastatin and nitric oxide synthase inhibitors must be used.
基金ThisprojectwassupportedbytheNationalNaturalScience FoundationofChina (No .39470 314 )
文摘To investigate the effect of advanced glycosylation end products (AGEs) on the activity of protein kinase C (PKC) in human peripheral blood mononuclear cells (PBMC) and to observe whether aminoguanidine (AG) can influence the effect of AGEs Methods After PBMC were isolated from human peripheral blood and incubated with different concentrations of AGEs BSA for various periods, total PKC activity in PBMC was determined by measuring the incorporation of 32 P from [γ 32 P] ATP into a special substrate using Promega PKC assay kit Results AGEs BSA increased the total PKC activity in PBMC from 83 43±6 57?pmol/min/mg protein to 116 8±13 82?pmol/min/mg protein with a peak at 15?min AGEs BSA also increased the total PKC activity in a concentration dependent manner from 83 1±6 4?pmol/min/mg protein (control) to 119 1±13 3?pmol/min/mg protein (control vs AGEs BSA 400?mg/L, P <0 01) Furthermore, AGEs BSA induced an elevation of PKC activity in a glycosylating time related manner, from 80 9±8 2 (control) to 118 3±11 5?pmol/min/mg protein (glycosylation for 12 wk, P <0 01) The total PKC activity stimulated by AGEs BSA pretreated with AG (100, 200?mg/L) was markedly lower than that of AGEs BSA group not pretreated with AG ( P <0 05, P <0 01) Conclusions AGEs BSA increased the total PKC activity in PBMC in a concentration and incubation time dependent manner The ability of AGEs BSA to stimulate PKC activity was markedly decreased by pretreatment of AGEs BSA with
文摘To study the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on renal alteration in diabetic rats Methods Insulin or aminoguanidine was administered to diabetic rats Blood glucose, hemoglobin A 1C (HbA 1C ), glomerular tissue extracts AGE (GTE AGE), PKC, glomerular basement membrane thickness (GBMT) and urine protein/creatinine (Pr/Cr) ratio in diabetic rats were measured and analysed Results Levels of blood glucose, HbA 1C and AGE, PKC activity, the Pr/Cr ratio and GBMT were all significantly increased ( P values all less than 0 01) in diabetic rats Insulin could decrease the formation of HbA 1C and AGE, and improve PKC activity Aminoguanidine had no influence on PKC activity ( P >0 05) although it decreased the formation of AGE Both drugs could delay the increase of urine Pr/Cr ratio and GBMT ( P <0 05 or P <0 01) Conclusions Chronic hyperglycemia may lead to an increase of PKC activity HbA 1C and AGE may not directly contribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GBM thickening It is important to inhibit the formation of AGE and reduce the PKC activity so as to prevent or delay the development of diabetic
