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Objectives: The study aimed to determine the effect of coffee intake on AGEs formation and platelet aggregation in diabetic Wistar rats. Methods: Coffee powder samples were used to prepare a 10% beverage. Diabetes mellitus was induced in the animals by administering 2% alloxan. All animal experiments were approved by the ethics committee for animal experiments under N°. 420/2012 and 536/2013. Diabetic and non-diabetic rats were divided into 6 groups treated and untreated with coffee (7.2 mL/Kg body weight) and aminoguanidine (AGE inhibiting agent) (100 mg/Kg body weight) for 50 days. After 50 days, the animals were fasted for 12 h and anesthetized (40 mg/Kg sodium pentobarbital) intraperitoneally. Blood samples were collected from the abdominal artery puncture. Hematological parameters (red cells, hemoglobin, hematocrit and leukocyte) and glycemic and HbA1c levels were measured. AGEs quantification (spectrofluorometric method) and the platelet aggregation test (aggregation of cuvettes in a four-channel platelet aggregometer) were also conducted. The rats' renal function was evaluated by measuring serum urea and creatinine. Results: Data showed that coffee intake had no effect on the hematological parameters. Fasting glucose and HbA1c dosage were significantly higher in diabetic animals compared to non-diabetic animals (confirmed the effectiveness of inducing and maintaining diabetic status). Results showed that coffee reduced AGE formation and platelet aggregation in our animal model, not altering the animals' renal function. Conclusions: These results suggest beneficial effects on vasculopathy, a common complication in diabetic patients.
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Objectives: To investigate the GABAergic and nitriergic mechanism involved in the anxiolytic-like profile of ethanolic extract of garlic (GE). Materials and Methods: Male Swiss albino mice were employed in the present study. Stress was produced in mice by immobilizing them for 6h. Elevated plus maze, light/dark box and social interaction test were used for the assessment of anxiety in mice. Concentrations of GABA in brain and nitrite level in plasma were estimated to determine the possible involvement of GABAergic and nitriergic mechanisms in the anxiolytic profile of GE. Results: The present study showed that the GE produced significant antianxiety- like activity in unstressed and stressed mice. In unstressed mice, GE significantly increased GABA levels, but could not produce any change in nitrite levels. Meanwhile, in stressed mice, GE significantly increased GABA levels along with a significant decrease in nitrite levels. Pre-treatment with aminoguanidine, an inducible nitric oxide synthase inhibitor, significantly enhanced the anxiolytic-like activity of GE, as compared to GE and aminoguanidine alone in stressed mice, but not in unstressed mice. On the other hand, pretreatment with 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, did not produce any significant change in antianxiety- like activity of GE in unstressed as well as stressed mice. Conclusion: It has been concluded that the garlic may possess anxiolytic- like activity and possess NOS inhibiting property in stressed mice, which may add to its status to be used in stress-induced anxiety conditions.
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Objective To observe the effects of quercetin liposome (LQ) on formation of advanced glycation end prod-ucts(AGEs)and receptor for advanced glycation end products (RAGE) in kidney of diabetic rats. Methods LQ was made by rotary evaporation, and the model of type 2 diabetic rats were established by being fed on high-sugar and high-fat diet combined with intraperitoneally injection of streptozotocin (STZ). Then type 2 diabetic rats were randomly divided into six groups:diabetic model group (group DM), low level of LQ group (group LQ-L ), medium level of LQ group (group LQ-M), high level of LQ group (group LQ-H), positive control group (group aminoguanidine, AG) and control group (group N). After 8 weeks of interventions, blood glucose, body weight, kidney hypertrophy index (KI), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured in each group. ELISA was used to detect serum AGEs, and 24 h urine albumin. The pathologi-cal change of glomerular basement membranes was observed by PAS staining and the expressions of AGEs in kidney was as-sessed by immunohistochemical method. The transcription level of RAGE mRNA in kidney was determined by RT-PCR. Re-sults Compared with the group N, the level of blood glucose, KI, BUN, Scr, serum AGEs and 24 h urine albumin were in-creased significantly in group DM, while the level of body weight decreased. Also the volume of kidney glomerulus increased and glomerular basement membranes thickened, the transcription levels of AGEs and RAGE mRNA in kidney tissue in-creased in DM group (P<0.05). Compared with group DM, the level of blood glucose, KI, BUN, Scr, serum AGEs and 24 h urinary albumin decreased, while the level of body weight increased in all three LQ groups. Meantime, the change of patho-logical morphology of glomerular basement membranes reduced and the expressions of AGEs and RAGE mRNA in kidney tissue decreased in all three LQ groups. All changes in the medium LQ dose group were more obvious than those of other two LQ groups (P<0.05). Conclusion Similar to AG, LQ has effect on inhibiting the action of proteinum unenzymatic glycosyl-ation and on decreasing the production of AGEs in serum as well as the expression of RAGE mRNA in kidney. Therefore, LQ play important protective role in kidneys of diabetic rats.
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Objective Recent studies have indicated that early brain injury is the leading cause of death in patients with subarachnoid hemorrhage ( SAH) .Our study investigated the role of aminoguanidine ( AG) in early brain injury after SAH . Methods Sixty-eight male SD rats were equally randomized into four groups of equal number :control, sham, SAH, and AG.The animals in the sham group were injected with isotonic saline solution , while those of the latter two groups with femoral artery blood ( FAB) and FAB+AG, respectively, into the pre-chiasmatic cistern to induce SAH. At 24 hours after modeling , all the rats were killed for HE staining , obtainment of behavioral neurological assessment ( BNA ) scores by Garcia, measurement of the apoptosis of neurons by TUNEL , and de-termination of the expressions of the iNOS and NSE proteins by West-ern blot. Results The results of HE staining showed the presence of more red blood cells in the subarachnoid cavity of the rats in the SAH group, with a significantly decreased BNA score ( 14.47 ± 0.62) as compared with those in the control (17.94 ±0.24), sham (17.59 ±0.51), and AG group (15.71 ±0.47) (P<0.05). The rate of positive cells was remarkably higher in the SAH group ([42.38 ±2.38]%) than in the control ([6.35 ±0.94]%), sham ([6.85 ±0.69]%), and AG group ([30.48 ±2.89]%) ( P<0.01), with significant differences among the latter three groups (P<0.05).The expressions of iNOS and NSE were markedly higher in the SAH group ([3.86 ±0.07] and [1.59 ±0.06]) than in the control (0 and[0.35 ±0.09]), sham ([2.96 ±0.34] and [0.38 ±0.08]), and AG group ([3.41 ±0.04] and [0.70 ±0.12]) ( P<0.05).Both the expression levels of iNOS and NSE were positively correlated with the rate of positive cells (r=0 .879 and 0.935, P<0.01). Conclusion AG can alleviate early brain injury after SAH in SD rats by improving the neuro-ethologic function , suppressing the apoptosis of neurons , and reducing the expressions of iNOS and NSE .
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Objective To investigate the treatment and mechanism of aminoguanidine in retina of diabetic of rats .Methods To-tal 60 rats were divided into control group(n=20) ,diabetic group(n=20) and aminoguanidine treatment group(n=20)which would be treated by aminoguanidine for 14 days .Then the eye tissue of rats were took after 14 days administration for pathological obser-vation(HE staining) ,and the induced nitric oxide synthase(iNOS) ,endothelial nitric oxide synthase(eNOS) ,nerve type of nitric ox-ide synthase(nNOS) level and the expression of differences content and expression were investigated by ELISA ,Western blot and PT-PCR .Results HE staining showed that retinal tissue defects decreased and neuronal cells of rats in aminoguanidine treatment group were increased and significant (P 0 .05) .Compared with diabetes group ,iNOS ,eNOS ,nNOS protein expression in the rat retina in aminoguanidine treatment group were reduced (P0 .05) .The iNOS mRNA expres-sion was lower than that of eNOS mRNA and nNOS mRNA in aminoguanidine treatment group .Conclusion Aminoguanidine can improve retinal tissue of diabetic rats with lesions ,the pathways may be selectively inhibit inducible nitric oxide synthase activity of iNOS .
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Background Many eye diseases such as central retinal artery occlusion,glaucoma and ischemic optic neuropathy,etc.lead to retinal ischemia-reperfusion injury (RIRI) and furthmore visual functional damage.It is neeessary to study the treatment of RIRI.Objective This study was to observe and discuss the influence of aminoguanidine on the retina morphological changes and its mechanism after RIRI.Methods Eighty clean healthy male Japanese white rabbits were randomly divided into normal injury group,RIRI group and aminoguanidine (AG)treated group.The model of RIRI was established by infusing saline solution into the anterior chamber to elevate intraocular pressure (IOP) in both RIRI group and AG group.AG was intraperitoneally injected in the models of the AG group,and normal saline solution was used at the same method in tbe normal group and the RIRI group.The fundus photography and fundus fluorescein angiography(FFA) were pertormed on the rabbits at the moment of retina ischemia and 6,24 and 72 hours after reperfusion.The parts of rabbits were sacrificed 1,6,24 and 72 hours after reperfusion,followed by the enucleation of the eyeballs.Retinal section was prepared for TUNEL examination to evaluate the apoptosis of retinal cells.Nitric oxide (NO) concentration in retina was detected with nitrate reductase,and the activity of inducible nitric oxide synthase (iNOS) was measured by colorimetric detection.The use of the animals followed the Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.Results The fundus photography and FFA showed that the retinal edema was more mild,and the percentage of vascular occlusion was lower in the AG treatment group than that in RIRI group and the amount and area of fluorescein leakage were also smaller than the treatment group.The numbers of TUNEL positive cells in the AG treatment group were less than those in the RIRI model group at 1,6,24 and 72 hours after experiment (F分组 =2762.37,P =0.00 ; F时间 =894.24,P =0.00).Numbers of TUNEL positive cells between adjacent time points were significantly different in both RIRI model group and AG treatment group (RIRI group:q =24.475,36.591,-20.37,P＜0.05;AG group:q =20.94,16.79,-6.92,P＜0.05),with the peak value at 24 hours after experiment.NO contents were significantly higher in the RIRI model group compared to AG group at various time points(q =3.84,4.01,8.91,3.75,P＜0.05),and those between adjacent time points showed significant differences (RIRI group:q=4.77,13.403,-10.29,P＜0.05;AG group:q=4.55,9.05,-5.08,P＜0.05).iNOS activity was significantly elevated in the RIRI model group compared with AG group(q=-3.74,-4.94,-6.53,-3.98,P＜0.05),and obvious differences also were seen between the adjacent time points in both two groups(RIRI group:q =8.43,6.71,-6.39,P＜0.05 ;AG group:q =4.16,5.08,-3.93,P＜0.05).Conclusions Aminoguanidine can protect the retinal function and morpbology from oxidative stress damage after RIRI by reducing the NO level and inhibiting the iNOS activity in retina.
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OBJECTIVE: The objective of this study was to evaluate the involvement of peripheral nitric oxide (NO) in vagotomy-induced pulmonary edema by verifying whether the nitric oxide synthases (NOS), constitutive (cNOS) and inducible (iNOS), participate in this mechanism. INTRODUCTION: It has been proposed that vagotomy induces neurogenic pulmonary edema or intensifies the edema of other etiologies. METHODS: Control and vagotomized rats were pretreated with 0.3 mg/kg, 3.0 mg/kg or 39.0 mg/kg of L-NAME, or with 5.0 mg/kg, 10.0 mg/kg or 20.0 mg/kg of aminoguanidine. All animals were observed for 120 minutes. After the animals' death, the trachea was catheterized in order to observe tracheal fluid and to classify the severity of pulmonary edema. The lungs were removed and weighed to evaluate pulmonary weight gain and edema index. RESULTS: Vagotomy promoted pulmonary edema as edema was significantly higher than in the control. This effect was modified by treatment with L-NAME. The highest dose, 39.0 mg/kg, reduced the edema and prolonged the survival of the animals, while at the lowest dose, 0.3 mg/kg, the edema and reduced survival rates were maintained. Aminoguanidine, regardless of the dose inhibited the development of the edema. Its effect was similar to that observed when the highest dose of L-NAME was administered. It may be that the non-selective blockade of cNOS by the highest dose of L-NAME also inhibited the iNOS pathway. CONCLUSION: Our data suggest that iNOS could be directly involved in pulmonary edema induced by vagotomy and cNOS appears to participate as a protector mechanism.
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Animals , Male , Rats , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III/metabolism , Nitric Oxide/metabolism , Pulmonary Edema/metabolism , Vagotomy/adverse effects , Enzyme Inhibitors/therapeutic use , Guanidines/therapeutic use , NG-Nitroarginine Methyl Ester/therapeutic use , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type III/antagonists & inhibitors , Pulmonary Edema/drug therapy , Pulmonary Edema/etiology , Pulmonary Edema/prevention & control , Rats, Wistar , Severity of Illness Index , Time FactorsABSTRACT
Trimethyltin chloride (TMT) has been used as a neurotoxin for inducing brain dysfunction and neuronal death. Neuronal death in the hippocampus by TMT may generate excessive nitric oxide, but there are few studies about nitric oxide synthase enzyme involved in the synthesis of nitric oxide. The purpose of present study is to analyze the TMT toxicity in each region of rat hippocampus. To evaluate the involvement of nitric oxide, we analyzed the effects of aminoguanidine known as a selective inhibitor for inducible nitric oxide synthase on behavioral changes and the hippocampus of rat by TMT toxicity. 6-week-old male Sprague-Dawley rats were administered with a single dose of TMT (8 mg/kg b.w., i.p.) and the control group was similarly administered with distilled water. TMT + aminoguanidine-treated groups were administered with aminoguanidine (10 mg/kg or 100 mg/kg b.w., i.p.) for 3 days prior to TMT injection. The rats were sacrificed 2 days after TMT administration. In the TMT-treated group, a number of cell losses were seen in CA1, CA3 and the dentate gyrus. In the TMT + aminoguanidine-treated group, neuronal death was seen in CA1 and CA3, but reduced in the dentate gyrus compared to the TMT-treated group. Western blot analysis showed that cleaved caspase-3 expression was increased in the TMT-treated group compared to the control group. However, the expression significantly declined in the TMT + aminoguanidine-treated group. The present findings suggest that inducible nitric oxide synthase is involved in neuronal death induced by TMT.
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Animals , Humans , Male , Rats , Blotting, Western , Brain , Caspase 3 , Dentate Gyrus , Guanidines , Hippocampus , Neurons , Nitric Oxide , Nitric Oxide Synthase , Nitric Oxide Synthase Type II , Rats, Sprague-Dawley , Trimethyltin Compounds , WaterABSTRACT
Avaliaram-se o papel do óxido nítrico (NO) por meio da inibição da enzima óxido nítrico sintase induzível (iNOS), após a adição da aminoguanidina (AG), na motilidade, no vigor e na integridade da membrana plasmática nos tempos de 15, 60, 120, 180, 240 e 300min e a atividade mitocondrial e a capacitação de espermatozoides bovinos após 300min de cultivo. Adicionaram-se diferentes concentrações (0,001, 0,01 e 0,1M) de AG durante a capacitação induzida pela heparina e 500μM de nitroprussiato de sódio (SNP, doador de NO) à concentração deletéria. A adição de 0,1M de AG diminuiu a motilidade e o vigor espermático e a integridade da membrana (P<0,05). A adição de SNP ao meio de cultivo com 0,1M de AG somente reverteu a integridade da membrana após 300min. A inibição da síntese de NO pela adição de AG não alterou a atividade mitocondrial. A percentagem de oócitos penetrados com espermatozoides tratados com 0,01 e 0,1M de AG diminuiu 20,3 e 100 por cento, respectivamente, em relação aos não tratados (controle) (P<0,05), contudo houve aumento de 15 por cento na percentagem de oócitos desnudados penetrados com espermatozoides capacitados em presença de 0,1M de AG. Conclui-se que a inibição da síntese de NO pela AG diminuiu a qualidade espermática durante a capacitação de espermatozoides bovinos in vitro, exceto a atividade mitocondrial. Somente a integridade da membrana foi revertida após adição de NO, sugerindo diferentes vias de ação do NO na qualidade espermática ao longo da capacitação in vitro de espermatozoides bovinos.
The role of nitric oxide (NO) was evaluated by inhibition of inducible nitric oxide synthase (iNOS), with aminoguanidine (AG) on motility, vigor, and plasmatic membrane integrity of bovine spermatozoa culture after 15, 60, 120, 180, 240, and 300min and on mitochondrial activity and capacitation after 300min, respectively. Different concentrations, 0.001, 0.01, and 0.1M of AG were added during the heparin induced capacitation and sodium nitroprusside (SNP, NO donor-500μM) to the deleterious concentration. The addition of 0.1M of AG diminished progressive motility, spermatic vigor, and membrane integrity (P<0.05). SNP addition to the 0.1M of AG did revert only plasmatic membrane integrity after 300min. Mitochondrial activity was not influenced by addition of AG. Percentage of penetrated oocytes after addition of 0.01 and 0.1M of AG diminished, 20.3 and 100 percent, respectively, in relation to the control oocytes (P<0.05). However, an increase of 15 percent was observed when denuded oocytes were used with 0.1M AG treated sperm (P<0.05). It was concluded that the inhibition of NO synthesis with aminoguanidine diminished sperm quality during in vitro capacitation of bovine spermatozoa, except the mitochondrial activity. Only membrane integrity was reverted with the addition of NO to culture medium, suggesting different pathways of NO action on bovine sperm quality during in vitro capacitation.
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Animals , Male , Cattle , Sperm Capacitation , Nitric Oxide Synthase/antagonists & inhibitors , Cattle , SpermatozoaABSTRACT
Objective: To observe the changes of visual evoked potential (VEP) in diabetic rats and the influence of nerve growth factor (NGF) and aminoguanidine (AG) on VEP. Methods: Diabetes was induced in adult male Wistar rats with streptozotocin (STZ). Rats were divided into normal control group (CON), diabetes model group (DM), NGF-treated group (D +N) and AG-treated group(D+A). VEP was measured during the 3rd month, 6th month, 9th month, and 12th month. Results: Compared with the CON group, all rest groups had longer latencies and lower amplitudes (P<0.01). During the 6th and 9th months, the latencies in group D+N and group D+A were significantly decreased (P<0.05) compared with DM group, and the amplitude was partially recoved during the 6th month. The changes during the 12th month were similar to those of the 9th month, except that the amplitude in D+A group was slightly higher than that in the DM group. Conclusion: NGF and AG can improve DM-induced elongation of VEP latency and decrease of VEP amplitude.
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Objective To evaluate the therapeutic effect and mechanism of specific inducible nitric oxide synthase(iNOS)aminoguanidine(AG)in rats with obstructive jaundice.Methods Forty male Wistar rats were divided randomly into four groups: normal control group, sham operation group, obstructive jaundice group and aminoguanidine therapeutic group.Each group had 10 rats.We assayed levels of liver function,hemobilirubin, endotoxin,lactic acid and malondialdehyde before and after therapy, and we also analyzed pathology of the liver and small intestine.Then we could explore the therapeutic effect of AG in rats with obstructive jaundice.Results The levels of endotoxin,lactic acid and malondialdehyde in blood increased progressively along with the pathological changes of the liver and small intestine.Each of the AG group parameters was significantly lower, and the pathological changes of liver and small intestine were improved.Conclusion AG could protect liver and small intestine by attenuating lipid peroxidative and endotoxemia,and provide a new way to cure obstructive jaundice.
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AIM: To investigate the effect of aminoguanidine (AG) on plasma and renal levels of angiogenesis Ⅱ (AngⅡ), and to identify the relationship of AGEs with AngⅡ in STZ-induced diabetic rats. METHODS: Wistar rats were randomly assigned to three groups. Diabetes was induced, rats were then received AG in treatment group. At the end of 12th week, urine albumin excretion rate (UAER) and calculate creatinine clearance (Ccr) were detected. Periodic acid-Schiff reagent was used to evaluate renal pathology. Plasma and renal AngⅡ were analyzed by radioimmunoassay and immunohistochemistry, respectively. RESULTS: AG treatment significantly prevented the increase in UAER (P<0.01), renal pathology (P<0.01), and level of renal AngⅡ (P<0.01). However, plasma concentration of AngⅡ was higher than that in diabetic rats without AG treatment (P<0.01). CONCLUSION: AG down-regulates renal Ang Ⅱ level, probably by reducing the formation of AGEs, which may be one of the renoprotective factors in diabetic nephropathy. More proofs are needed to identify the result that plasma AngⅡ concentration increases in DMA group.
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Nitric oxide (NO) has both neuroprotective and neurotoxic effects depending on its concentration and the experimental model. We tested the effects of NG-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) inhibitor, and aminoguanidine, a selective inducible NOS (iNOS) inhibitor, on kainic acid (KA)-induced seizures and hippocampal CA3 neuronal death. L-NAME (50 mg/kg, i.p.) and/or aminoguanidine (200 mg/kg, i.p.) were administered 1 h prior to the intracerebroventricular (i.c.v.) injection of KA. Pretreatment with L-NAME significantly increased KA-induced CA3 neuronal death, iNOS expression, and activation of microglia. However, pretreatment with aminoguanidine significantly suppressed both the KA-induced and L-NAME-aggravated hippocampal CA3 neuronal death with concomitant decreases in iNOS expression and microglial activation. The protective effect of aminoguanidine was maintained for up to 2 weeks. Furthermore, iNOS knockout mice (iNOS-/-) were resistant to KA-induced neuronal death. The present study demonstrates that aminoguanidine attenuates KA-induced neuronal death, whereas L-NAME aggravates neuronal death, in the CA3 region of the hippocampus, suggesting that NOS isoforms play different roles in KA-induced excitotoxicity.
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Animals , Mice , Guanidines , Hippocampus , Kainic Acid , Mice, Knockout , Microglia , Models, Theoretical , Neurons , NG-Nitroarginine Methyl Ester , Nitric Oxide , Nitric Oxide Synthase , Protein Isoforms , SeizuresABSTRACT
Objective To investigate the thyroid ultrastructural pathological changes of diabetes mellitus (DM) rats as well as the intervention effects of insulin and aminoguanidine. Methods Totally 87 rats were treated with streptozotocin to establish DM animal models and divided into DM group(n=27),insulin intervention group(n=32) and aminoguanidine intervention group(n=28),25 rats were taken as normal controls. Twelve and 20 weeks after the animal model establishment, animals were sacrificed, thyroid tissue was taken and ultrastructure was observed. Results In the thyroid of DM rats, follicular epithelial cells present as applanate shape, microvilli were depleted, rough endoplasmic reticulum dilated to irregular vesicular. None pinocytotic vacuole and casual primary or secondary lysosome were seen. Follicular cavity was dilated, colloid in the cavity had higher electronic-density. Interstitial edema, capillary base lamian was thickened at different stage. Proteo-substance deposition with granulo-shape, cloud shape or homogeneity appeared. The number of thyroid parafollicular cells increased. But endocrine granule in parafollicular cells was few. When compared with DM group, the thyroid tissue injury of insulin intervention group and aminoguanidine intervention group were lessened to different degree. Conclusion The hypofunctional thyroid follicular cells, large quantity of proteo-substance deposition in the interstitium and increased parafollicular cells of DM rats may be related with hyperglycemia toxicity. Insulin and aminoguanidine treatment have some protection effects.
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It has been demonstrated that inhibitors of advanced glycation end products (AGE), such as aminoguanidine, can suppress peritoneal AGE in rats on peritoneal dialysis (PD). However, it is unknown whether late administration of a putative crosslink breaker, alagebrium, could reverse peritoneal AGE. We therefore compared alagebrium with aminoguanidine in their ability to reverse peritoneal AGE in rats on PD. Male Sprague-Dawley rats were randomly divided into 3 groups: group I dialyzed with 4.25% glucose solution for all exchanges; group II dialyzed with 4.25% glucose solution containing aminoguanidine, and group III dialyzed with 4.25% glucose solution containing alagebrium for last 8 weeks of 12-week dialysis period. Dialysis exchanges were performed 2 times a day for 12 weeks. Immunohistochemistry was performed using a monoclonal anti-AGE antibody. One-hour PET was performed for comparison of transport characteristics. The immunolabelling of AGE in peritoneal membrane was markedly decreased in the alagebrium group. Consistent with this, the alagebrium group exhibited significantly higher D/Do glucose and lower D/P urea, suggesting low peritoneal membrane transport. But there were no significant differences between the control and the aminoguanidine group. These results suggest that the alagebrium may be the optimal therapeutic approach, compared with treatment with inhibitors of AGE formation, in rats on PD.
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Animals , Male , Rats , Biological Transport , Body Weight , Cell Membrane/metabolism , /metabolism , Guanidines/metabolism , Immunohistochemistry/methods , Peritoneal Dialysis/methods , Peritoneum/metabolism , Permeability , Rats, Sprague-DawleyABSTRACT
Objective To investigate the effect of inducible nitric oxide synthase(iNOS) inhibitor aminoguanidine on pancreas islets cultured with cytokines TNF-? and IL-1? in rats.Methods Islets isolated from Wistar rats were purified and cultured.According to whether cytokines TNF-?,IL-1? and aminoguanidine were added into the medium respectively or not,islets were divided into 4 groups: cultured with islet only was taken as blank control group,cultured with TNF-?+IL-1? as cytokine group,cultured with aminoguanidine as aminoguanidine group,and cultured with TNF-?+IL-1? and aminoguanidine as aminoguanidine+cytokine group.NO level in culture medium and iNOS activity in islets tissue(Test Kit),apoptosis(TUNEL method) and viability of islets cell(acridine orange/ethidium bromide stain),and the function of islets(insulin release test) were measured.Results Compared with blank control group,the activity of iNOS in islet tissue and level of NO in culture medium increased,and the mass mortality and apoptosis appeared in islet cells,while insulin secretion decreased in cytokine group(P
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Objective:To investigate the effects of Jiejufushenning on advanced glycation end products(AGEs)in serum and expression of receptor for advanced glycation end products(RAGE) in kidney in diabetic rats.Methods:Diabetic SD rats were induced by injection of streptozotocin,then the diabetic rats were randomly divided into four groups:diabetic control group(group B),Jiejufushenning group(group C),aminoguanidine group(group D),Jiejufushenning and aminoguanidine group(group E),age-matched norma1 SD rats served as norma1 contro1 group(group A).After 12 weeks of treatment by corresponding intervention,blood glucose,renal function,the quantitation of urine protein of 24 hours(24hPro)and urine creatinine were determined by the normal methods.The levels of AGEs in serum were determined by fluorospectrophotometry,and the expressions of RAGE in kidney were determined by immunohistochemical methods.Results:The levels of blood glucose,urea nitrogen(BUN),serum creatinine(Scr)and 24hPro in rats of group C,group D and group E were obviously lower than those of group B,but higher than those of group A;The levels of urine creatinine of group C,D and E were obviously higher than that of group B(P
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PURPOSE: To evaluate the effect of a combined treatment with aminoguanidine (AG) and methylprednisolone (MP) on the neurological recovery after a spinal cord injury (SCI). MATERIALS AND METHODS: SCI models (weight-drop) of Sprague Dawley rat were divided into 4 groups after the SCI. Group I was injected with normal saline, Group II with MP, Group III with AG and Group IV with MP and AG. The behavioral and immunohistochemical changes along with RT-PCR of TNFRI, TNFRII, XIAP, IL-6, and IL-6R were analyzed quantitatively and compared. RESULTS: At 7 days, motor recovery was observed in groups II, IV, III, and I with the level of improvement increasing in that order. Neuron cells were observed in groups II, IV=III, and I. TNFRI was not expressed in group I, but was expressed at a similar level in groups II, III and IV. TNFRII was expressed the most in group II but was not expressed in group I. The level of XIAP expression was similar to that of TNFRII. Groups II and IV showed almost no IL-6 expression, while groups I and III showed similar levels of expression. IL-6-R showed an opposite pattern to IL-6. CONCLUSION: Both drugs have a neuroprotective effect but there was no synergistic effect for simultaneous administration.
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Animals , Rats , Interleukin-6 , Methylprednisolone , Neurons , Neuroprotective Agents , Spinal Cord Injuries , Spinal CordABSTRACT
BACKGROUND: Clinically relevant cerebral ischemia is encountered most frequently as a cardiac arrest or as single or multiple occlusions of the intracranial or extracranial cerebral arteries. Yamaguchi et al. has introduced a one-stage anterior approach to occlude the common carotid arteries (CCAs) and vertebral arteries (VAs). METHODS: We used a 2-stage anterior approach for producing transient global ischemia by 4-vessel occlusion (4-VO). Four to five days after electrocauterization of two VAs using the anterior neck approach, two CCAs were clipped for 10 min under anesthesia. Aminoguanidine (100 mg/kg) was administered intraperitoneally immediately after 4-VO, and then twice a day for three consecutive days. Cresyl violet staining and immunohistochemical analysis for the expression of GFAP, CD11b, nitrotyrosine, iNOS, and Bax were performed, using brain slices obtained from the rats that were sacrificed 1, 3, 5 and 7 days after reperfusion. RESULTS: Aminoguanidine reduced neuronal cell death in the CA1 region of the hippocampus. Expression of GFAP, CD11b, nitrotyrosine, iNOS, and Bax were significantly increased in the CA1 region of the hippocampus three days after 4-VO. CONCLUSIONS: We believe that modified 4-VO is a good method to study transient forebrain ischemia as it is simple and inexpensive to perform and can be utilized without stereotaxis, a pivoting dissection microscope, EEG, a laser flowmeter or the use of Mongolian gerbils.
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Animals , Rats , Anesthesia , Brain , Brain Ischemia , Carotid Artery, Common , Cell Death , Cerebral Arteries , Electroencephalography , Flowmeters , Gerbillinae , Heart Arrest , Hippocampus , Ischemia , Neck , Neurons , Prosencephalon , Reperfusion , Vertebral Artery , ViolaABSTRACT
Objective To evaluate the therapeutic effects of aminoguanidine(AG) on cerebral ischemia-reperfusion damage in rats. Methods The intravascular thread models with 2 h of occlusion and 22 h of reperfusion were made in the rats.The brain infarction size and the degree of blood brain barrier(BBB) disruption in the ischemic regions were evaluated by staining with 2,3,5-triphenyl tetrazolium chloride and observing with Evans blue fluorescence microscope.HE staining was utilized for observing neutrophil infiltration. Results The brain infarction(volume,) the area of BBB disruption and the degree of neutrophil infiltration were dramatically decreased in the treatment group as compared to the control group(P