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

Abstract

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.