Potent protective effect of melatonin on chromium(VI)-induced DNA single-strand breaks, cytotoxicity, and lipid peroxidation in primary cultures of rat hepatocytes.
Incubation of primary cultures of rat hepatocytes with K2Cr2O7 plus the pineal hormone melatonin resulted in a marked decrease in cellular levels of DNA single-strand breaks caused by K2Cr2O7. Cellular treatment with melatonin also suppressed both dichromate-induced cytotoxicity, as evaluated by the leakage of lactate dehydrogenase, and lipid peroxidation, as monitored by malondialdehyde formation. In addition, treatment with melatonin attenuated the suppression of the levels of vitamins E and C as well as the inhibition of catalase activity attributed to K2Cr2O7. However, melatonin had no influence on cellular level of glutathione and the activity of glutathione reductase, glutathione peroxidase, superoxide dismutase, and alkaline phosphatase suppressed by dichromate. Under the same experimental conditions, cellular uptake and distribution of Cr were not affected by melatonin. Electron spin resonance (ESR) studies showed that melatonin did not affect the formation of Cr(V) complexes in the reaction of K2Cr2O7 with reduced glutathione; however, melatonin caused a 25% decrease in the levels of Cr(V)-related hydroxyl radicals in vitro. These results indicate that melatonin protects cells from Cr(VI)-induced DNA strand breaks, cytotoxicity, and lipid peroxidation, possibly through its ability to increase cellular levels of vitamins E and C as well as catalase activity and/or to directly scavenge toxic hydroxyl radicals in cells.
Susa
N
N
Department of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori, Japan.
Ueno
S
S
Furukawa
Y
Y
Ueda
J
J
Sugiyama
M
M
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000633:toxicity; D001205:Ascorbic Acid / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002857:Chromium / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D011192:Potassium Dichromate / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000378:metabolism
D000890:Anti-Infective Agents; D004277:DNA, Single-Stranded; D002857:Chromium; D014810:Vitamin E; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D008550:Melatonin; D001205:Ascorbic Acid; D011192:Potassium Dichromate