EXPERIMENTAL DIABETES MELLITUS AND OXYGEN FREE RADICALS
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Oxygen free radicals (OFRs) have been implicated as a causal or contributory factor in various disease states. These oxygen radicals are highly reactive species and cause cellular damage. In diabetes, various sources may lead to an increase in the production of OFRs. These sources include glucose oxidation, autoxidative glycosylation, alteration in sorbitol pathway activity and changes in level of inflammatory mediators. It is hypothesized that the complications in diabetes mellitus could be due to an increase in the levels of OFRs as a result of its increased production and/or its decreased destruction. To test this hypothesis diabetes was induced in male Sprague Dawley rats by streptozotocin (STZ). The rats were sacrificed after 1st, 2nd, 3rd, 4th, 5th and 6th week (wk) of development of diabetes. The various tissues (liver, heart, pancreas, aorta and kidney) and blood involved either in the development or in the complications were selected for the study. Plasma glucose levels were measured to confirm the diabetic state of the animal. Malondialdehyde (MDA) content (product of lipid peroxidation) and antioxidant enzymes [Catalase (CAT), Glutathione-peroxidase (GSH-Px) and Superoxide dismutase (SOD-Total, Cu-Zn and Mn)] were measured in blood and tissues in control and streptozotocin induced diabetic rats. An increase of 3-4 fold in plasma glucose levels and decrease in body weight was observed in diabetic rats as compared to controls at each time interval. MDA levels were increased in all tissues in the diabetic state. With the progression of the disease liver, aorta, kidney and blood showed significant increases in MDA, being maximal on the 6th wk. However, the pancreas showed the highest MDA levels up to the 4th wk. Catalase activity increased significantly in all diabetic tissues as compared to controls at most of the time intervals except the kidney which showed a significant increase on the 1st wk and after that the activity decreased. In aorta and blood the activity increased with time. However, activity decreased in the liver and the heart on the 5th and 6th wk as compared to the 4th wk. Its activity in pancreas decreased with time. GSH-Px activity increased significantly in all the diabetic tissues as compared to controls. Liver, aorta and blood showed increased activity of GSH-Px with progression of disease. Heart and pancreas showed lower activity on the 5th and 6th wk as compared to the 4th wk. The kidney did not show any change. Total SOD and Cu-Zn SOD activity in diabetic tissues showed a significant increase as compared to controls at most of the time intervals. Liver, pancreas and aorta showed decreasing trend after 4 wks; however heart and kidney showed no change. Mn-SOD activity was variable in control and diabetic tissues. While the activity decreased in liver and heart at 4th wk, it increased in heart at 6th wk. No changes were observed in pancreas and kidney. In general, pancreas and aorta showed the lowest antioxidant enzyme activities and higher MDA content as compared to other tissues. The results of the present study suggest that oxidative stress is associated with the diabetic state and starts at early onset of disease. The marked changes in MDA and antioxidant enzymes suggest higher production of OFRs in diabetes which may cause oxidative damage to tissues leading to various complications.