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Protective effect of melatonin on paraquat-induced cytotoxicity in isolated rat hepatocytes
Unit of Pharmacology and Toxicology, Department of Animal Medicine and Health, Faculty of Veterinary, University of Extremadura, Cáceres, Spain
Unit of Pharmacology and Toxicology, Department of Animal Medicine and Health, Faculty of Veterinary, University of Extremadura, Cáceres, Spain; Unit of Pharmacology and Toxicology, Faculty of Veterinary, Avda. de la Universidad s/n, 10071 Cáceres, Spain mpmiguez{at}unex.es Paraquat (PQ) is a known herbicide that causes acute cell injury by undergoing redox cycling. In previous reports, it has been reported that melatonin reduces PQ-induced hepatic toxicity in vivo, but, at the moment, there is no evidence that this effect occurs in this organ in vitro. In the present study we examined the effect of melatonin on PQ-induced oxidative damage in the liver using a hepatocyte suspension as a biological model. Preincubation of hepatocytes with melatonin (0.5, 1 or 2 mM), 30 min prior to PQ (10 mM) addition, prevented in a dose-and time-dependent manner the loss of viability, the leakage of lactate dehydrogenase, depletion of intra-cellular glutathione and malondialdehyde accumulation induced by the herbicide. Melatonin at the highest dose assayed (2 mM) completely prevented cell damage caused by PQ. These effects of melatonin are similar to those described in studies carried out in vivo. These results confirm that melatonin confers protection against PQ-induced hepatic oxidative stress and show that freshly isolated hepatocyte suspension is an adequate in vitro system for evaluating the cytoprotective effects of melatonin on oxidative injury caused by xenobiotics.
Key Words: hepatocytes • melatonin • oxidative stress • paraquat
Human & Experimental Toxicology, Vol. 24, No. 9,
475-480 (2005) |
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