Potent protective effect of melatonin on chromium(VI)-induced DNA single-strand breaks, cytotoxicity, and lipid peroxidation in primary cultures of rat hepatocytes

Toxicology and Applied Pharmacology
N SusaM Sugiyama

Abstract

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, cyt...Continue Reading

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