Melatonin reduces phenylhydrazine-induced oxidative damage to cellular membranes: evidence for the involvement of iron.
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.
Karbownik
M
M
Department of Cellular and Structural Biology, University of Texas Health Science Center, Mail Code 7762, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Reiter
R J
RJ
Garcia
J J
JJ
Tan
D
D
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000031:analogs & derivatives / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010659:Phenylhydrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016166:Free Radical Scavengers; D010659:Phenylhydrazines; C030299:phenylhydrazine; D008315:Malondialdehyde; D007501:Iron; D008550:Melatonin; D001205:Ascorbic Acid