Effect of melatonin on phase I and II biotransformation enzymes in streptozotocin-induced diabetic rats

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

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3 Scopus citations


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-hydroxybiphenyl in liver of normal rats. Hepatic glutathione S-transferase activity 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.

Original languageEnglish (US)
Pages (from-to)277-283
Number of pages7
JournalInternational Journal of Toxicology
Issue number4
StatePublished - Jan 1 2000


  • Antioxidant
  • Biotransformation
  • Diabetes Mellitus
  • Intestine
  • Kidney
  • Liver
  • Melatonin
  • Rat
  • Spleen

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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