Comparative Study Of The Effects Of Various Antioxidants On Oxidative Stress In The Early Stage Of Alloxan-Induced Diabetic Rats

Objective: To investigate the variations of oxidative stress, glycometabolism, lipometabolism, renal function and histopathology of pancreas, liver and kidney in the early stage of alloxan-induced diabetic rats.Methods: Sparague-Dawley rats were randomly divided into normal control (NC) group and diabetes (DM) group. Alloxan(200mg/kg) was adiministered by i.p. to induce the diabetic models of rats. After 14 days, the concentrations of malondialdehyde(MDA), nitric oxide(NO), and the activity of antioxidant enzymes including superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) in serum and tissues (liver, kidney, pancreas, muscle) were measured, respectively. Other diabetic related pathophysiologic parameters such as blood glucose, blood lipid, kidney weight/body weight ratio, blood urea nitrogen, serum creatinine and histopathology of pancreas, liver and kidney were observed as well, respectively.Results: The concentrations of MDA and NO and the activity of GSH-Px in serum and tissues of liver, kidney, pancreas of DM group were increased significantly compared with NC group, respectively, while the activity of SOD decreased significantly, otherwise, both the concentrations of MDA, NO and the activity of GSH-Px, SOD in muscle tissues of DM group were increased significantly compared with NC group. DM group showed a significant increasing of blood glucose, total cholesterol, triglyceride, kidney weight/body weight ratio, blood urea nitrogen compared with NC group, respectively, there was no statistical significant difference of serum creatinine to be observed between DM and NC group. Histopathological study of pancreas showed significant difference in DM group as compared to NC group, but without significant variations to be observed in liver and kidney.Conclusion: These data confirm that there was severe oxidative stress state existed in early of stage of diabetic rats induced by alloxan. Oxidative stress probably plays an important role in the development of diabetes and its chronic complications.Objective: To investigate the effects of melatonin, vitamin E and glutathione on oxidative stress, glycometabolism, lipometabolism and renal function in the early stage of alloxan-induced diabetic rats.Methods: Sparague-Dawley rats were randomly divided into five groups: (1)Normal control(NC) group; (2)diabetic control (DMC)group, induced by alloxan i.p.; (3)melatonin group, diabetic rats treated with melatonin (DM+M); (4)vitamin E group, diabetic rats treated with vitamin E (DM+E); (5)glutathione group, diabetic rats treated with glutathione(DM+G). Melatonin(2mg/kg), vitamin E(100mg/kg) or glutathione(100mg/kg) was administered i.p. respectively for 14 consecutive days after induction of diabetes by alloxan(200mg/kg i.p.). The concentrations of malondialdehyde (MDA), nitric oxide (NO), and the activity of antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum and tissues (liver, kidney, pancreas, muscle) were measured, respectively. Other diabetic related pathophysiologic parameters such as blood glucose, blood lipid, kidney weight/body weight ratio, blood urea nitrogen and serum creatinine were observed as well, respectively.Results: Either treated with melatonin, vitamin E or glutathione, in tissues of liver, kidney, pancreas, muscle and serum of diabetic rats, the MDA and NO levels were decreased significantly, and the elevated GSH-Px activity decreased in tissues, while SOD activity increased significantly in liver, kidney and pancreas, respectively, compared with DMC group, except that glutathione had no effect on liver SOD activity. The antioxidative effects of melatonin were more efficient than that of vitamin E and glutathione in kidney and pancreas, but vitamin E was more potent than melatonin and glutathione in liver, whereas glutathione was better than melatonin and vitamin E in muscle. Melatonin, vitamin E and glutathione also caused a significant decrease of total cholesterol and triglyceride, but there were no significant difference to be observed in blood glucose and serum creatinine compared with DMC group. The elevated kidney weight, kidney weight/body weight ratio, blood urea nitrogen were reduced significantly by melatonin, but without significant variations to be observed in the vitamin E and glutathione treated group.Conclusion: These data suggest that melatonin enhanced the antioxidative activity and inhibited the oxidative stress in diabetic rat induced by alloxan; the antioxidative ability of melatonin is more efficient than vitamin E and glutathione. Melatonin plays a protective effect on the kidney of diabetic rat. Those antioxidative effects of three antioxidants may play a beneficial role to the metabolism of lipid.