| Objective To study the protective effects of Aminoguanidine(Ag) and Resveratrol(Res) and combination of two drugs(Ag+Res) on oxidative stress in liver and diabetic hepatopathy of diabetic rats.Methods Fifty male Wistar rats (three months old) were fed by high-glucose-high-fat diet, the rats were randomly divided into five groups when they grow up to about 400g.The model of diabetes mellitus was set up by injection of streptozotocin(35mg·kg-1body weight) in freshly prepared 0.1mol·L-1 sodium citrate in four groups. The diabetic rats were randomly divided into Diabetes Mellitus control rats(group DM), Aminoguanidine (50mg·kg-1·d-1) treated group (group Ag), Resveratrol (10mg·kg-1·d-1) treated group (group Res) and combination of two drugs (50mg·kg-1·d-1 Ag+10mg·kg-1·d-1 Res )treated group(group Ag+Res). Both diabetes mellitus control rats (group DM) and normal rats as control (group NC) were treated daily with same volume vehicle. The rats were killed by exsanguination 9 week after treatment. We measured malondialdehyde(MDA) as biomarkers of lipid peroxidation, and activities of the antioxidant enzymes Cu/Zn superoxide dismutase(Cu/Zn -SOD)and total antioxidant capacity(T-AOC) in liver homogenate and mitochondria. The levels of fasting blood glucose, alanine aminotransferase(ALT) activity, aspartate aminotransferase(AST) activity and triglyceride(TG) and total cholesterol(TC)in serum were measured. The content of hydroxyproline in serum and activity of cytochrome P450 2E1 in liver mitochondria were detected by chromatometry. The pathologic changes 6f liver tissues were observed by light microscopic examination and electron microscopy examination.Results 1.The contents of liver homogenate and mitochondria MDA in group DM were significantly higher than that in the group NC (P<0.01), the levels of liver homogenate and mitochondria Cu/Zn-SOD and T-AOC were significantly decreased in group DM as compared with group NC (P<0.05, P<0.01), it was also mentioned these biomarkers in diabetic rats treated with Aminoguanidine, Resveratrol and combination of two drugs were significantly improved(P<0.05, P<0.01). 2. The level of fasting blood glucose of diabetic rats was significantly higher than that in the group NC (P<0.01) , no significant difference was found between the groups treated with different drug and group DM. 3. The levels of ALT, AST, TG and TC in serum of group DM rats were significantly increased as compared with group NC (P<0.05, P<0.01) , but different protective effects were shown between three groups treated with different drugs. 4. Both Aminoguanidine and Resveratrol can decrease the content of hydroxyproline in serum and activity of cytochrome P450 2E1 in liver mitochondria of diabetic rats compared with group DM (P<0.05). 5. The protective effects of Aminoguanidine and Resveratrol and combination of two drugs on diabetic hepatopathy of rats were also confirmed by light microscope examination and transmission electron microscope examination.Conclusion The unbalance of oxidantion and antioxidantion in diabetic rats was discovered in present work, which indicated oxidative stress may play an important role in the progress of diabetic hepatopathy. Both Aminoguanidine and Resveratrol can effectively decrease activity of cytochrome P450 2E1 and prevent lipid peroxidation in liver mitochondria and remedy pathological changes of diabetic rats. Combination of two drugs may have cooperation therapeutic efficacy. |
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