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International Journal of Toxicology
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Effect of Melatonin on Phase I and II Biotransformation Enzymes in Streptozotocin-Induced Diabetic Rats

Alice C. Maritim

Moi University, Eldoret, Kenya

Brian H. Moore

Medical Sciences Program, Indiana University School of Medicine, Bloomington, Indiana, USA

Ruth A. Sanders

Medical Sciences Program, Indiana University School of Medicine, Bloomington, Indiana, USA

John B. Watkins, III

Medical Sciences Program, Indiana University School of Medicine, Bloomington, Indiana, USA

Melatonin, a pineal secretory product known to be a scavenger of oxygen radicals, is widely used as a dietary supplement, although its toxicity has not been well characterized. Melatonin was administered (10 mg/kg IP in gum tragacanth, once a day for 4 successive days) to normal and 30-day streptozotocin-induced diabetic male Sprague-Dawley rats, after which activities of phase I and phase II biotransformation enzymes were assessed in the liver, kidney, intestine, and spleen. Most melatonin-induced effects were seen in the liver, and a few in extrahepatic tissues. In the liver, the effects of diabetes were reversed in two instances: hydroxylation of benzo[a]pyrene and glutathione S-transferase activity toward 1-chloro-2,4-dinitrobenzene. In contrast to its effect on the phase I enzymes studied, whose activities were inhibited or unaffected by melatonin treatment, this treatment led to increased activity of glucuronyl transferase toward 4-methylumbelliferone in intestine of diabetic rats and toward 4-hydroxybiphenylin liver of normal rats. Hepatic glutathione S-transferaseactivity was also induced in normal rats after melatonin treatment, though the diabetic induction of this enzyme activity was reversed by melatonin. These results suggest that in addition to being a radical scavenger, melatonin, after 4 days of administration, does not induce the phase I enzymes studied, but may induce some hepatic phase II enzymes in normal but not diabetic rats.

Key Words: Antioxidant • Biotransformation • Diabetes Mellitus • Intestine • Kidney • Liver • Melatonin • Rat • Spleen

International Journal of Toxicology, Vol. 19, No. 4, 277-283 (2000)
DOI: 10.1080/10915810050202088
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