Effects of Melatonin on Oxidative Stress in Streptozotocin-Induced Diabetic Rats

Abstract

Oxidative stress plays an important role in diabetes and other oxygen-related diseases. Melatonin, a pineal hormone thought to be a scavenger of oxygen radicals and a potentially advantageou s ther- apeutic agent in diseases having oxidative stress, was administered (10 mg / kg ip, in gum tragacanth to prolong its absorption, once a day for 4 successive days) to normal and 30-day streptozotocin induced diabetic Sprague-Dawley rats, after which markers of ox- idative stress were assessed in the liver, kidney, intestine, and spleen. Alanine and aspartate aminotransferase activities in serum, which were increased after diabetes, were not increased further by melato- nin administration, indicating that there was no melatonin-related liver toxicity. Most melatonin-induced effects were seen in the liver, and very few in extrahepatic tissues. In livers of diabetic rats, re- duced concentration of nitrite and increased lipid peroxidation were both restored to normal levels following treatment with mela- tonin. Hepatic glutathione peroxidase activity was not changed in diabetics, but was decreased after melatonin administration in both normal and diabetic animals. Total glutathione concentra- tions were signi® cantly decreased in livers of all diabetics and were not normalized by melatonin treatment. Hepatic superoxide dis- mutase activity was elevated following melatonin dosing in normal rats, but dropped below normal levels in diabetic rats and was not restored by melatonin treatment. Glutathione S -transferase activ- ity was higher than normal in melatonin-dosed normal rat livers. These results suggest that after 4 days of administration, melatonin may enable various enzymes of the hepatic antioxidative defense system to better detoxify harmful oxygen radicals without produc- ing overt toxicity in a disease such as diabetes.