Effects of melatonin on oxidative stress in streptozotocin-induced diabetic rats

Alice C. Maritim, Brian H. Moore, Ruth A. Sanders, John B. Watkins

Research output: Contribution to journalArticle

30 Scopus citations


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 advantageous therapeutic 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 oxidative 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 melatonin 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, reduced concentration of nitrite and increased lipid peroxidation were both restored to normal levels following treatment with melatonin. Hepatic glutathione peroxidase activity was not changed in diabetics, but was decreased after melatonin administration in both normal and diabetic animals. Total glutathione concentrations were significantly decreased in livers of all diabetics and were not normalized by melatonin treatment. Hepatic superoxide dismutase 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 activity 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 producing overt toxicity in a disease such as diabetes.

Original languageEnglish (US)
Pages (from-to)161-166
Number of pages6
JournalInternational Journal of Toxicology
Issue number3
StatePublished - May 1 1999


  • Antioxidant
  • Catalase
  • Diabetes
  • Free Radical
  • Glutathione
  • Glutathione Peroxidase
  • Glutathione Reductase
  • Glutathione S-Transferase
  • Lipid Peroxidation
  • Melatonin
  • Oxidative Stress
  • Rat
  • Streptozotocin
  • Superoxide Dismutase
  • Thiobarbituric Acid

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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