Melatonin reduces phenylhydrazine-induced oxidative damage to cellular membranes: Evidence for the involvement of iron

Małgorzata Karbownik, Russel J. Reiter, Joaquin J. Garcia, Dun Xian Tan

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Phenylhydrazine and iron overload result in augmented oxidative damage and an increased likelihood of cancer. Melatonin is a well known antioxidant and free radical scavenger. The aim of this study was to determine whether melatonin would protect against phenylhydrazine-induced oxidative damage to cellular membranes and to evaluate the possible role of iron in this process. Changes in lipid peroxidation and microsomal membrane fluidity were estimated after the treatment of rats with phenylhydrazine (15 mg/kg body weight, daily, 7 days) alone and melatonin or ascorbic acid (15 mg/kg body weight, two times daily, 8 days), or their combination. Additionally, lipid peroxidation was measured in liver homogenates from untreated and melatonin or ascorbic acid-treated rats in vivo and exposed to iron in vitro. Melatonin, but not ascorbic acid, reduced phenylhydrazine-induced lipid peroxidation in vivo in spleen (3.16 ± 0.06 vs. 3.83 ± 0.12 nmol/mg protein, P < 0.05) and plasma (7.73 ± 0.52 vs. 9.96 ± 0.71 nmol/ml, P < 0.05) and attenuated the decrease in hepatic microsomal membrane fluidity (1/polarization, 3.068 ± 0.007 vs. 3.027 ± 0.008, P < 0.05). In vitro exposure to iron significantly enhanced the lipid peroxidation in liver homogenates from untreated (3.34 ± 0.75 vs. 1.25 ± 0.28, P < 0.05) or ascorbic acid-treated rats (2.72 ± 0.39 vs. 0.88 ± 0.06, P < 0.05) but not from melatonin-treated rats (1.49 ± 0.55 vs. 0.68 ± 0.20, NS). It is concluded that free radical mechanisms are involved in the toxicity of phenylhydrazine and that the antioxidant melatonin, but not ascorbic acid, reduces the toxic affects of phenylhydrazine in vivo and of iron in vitro in cell membranes. Therefore, melatonin co-treatment in conditions of iron overload may prove beneficial. (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)1045-1054
Number of pages10
JournalInternational Journal of Biochemistry and Cell Biology
Issue number10
StatePublished - 2000


  • Cancer
  • Iron
  • Melatonin
  • Membrane oxidative damage
  • Phenylhydrazine

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology


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