Melatonin protects on toxicity by acetaminophen but not on pharmacological effects in mice

Biological & Pharmaceutical Bulletin
Syu-ichi KannoMasaaki Ishikawa

Abstract

The pineal gland and its main hormone, melatonin (MLT), are involved in a variety of physiological processes. MLT is a member of the indolamine family and has significant antioxidative activity. Acetaminophen (AA) is the most widely used medication in the world, both by prescription and over the counter. In large doses, AA is hepatotoxic causing oxidative stress and lipid peroxidation. Therefore, antioxidants have been used to protect against the toxicity of AA. Here, we examined in vitro and in vivo the protective effects of MLT against AA-induced toxicity in mice. MLT (100 microM) had a significant protective effect on the AA (7 mM)-induced loss of cell viability in mouse primary cultured hepatocytes as determined using the 3H-thymidine incorporation assay and MTT assay. The AA-induced generation of reactive oxygen species (ROS) peaked at 6 h and was followed by an increase in lipid peroxidation at 12 h in hepatocytes. MLT (0.1, 1, 10 or 100 microM) dose-dependently attenuated the increase in both production of ROS and lipid peroxidation by AA. Similarly, in vivo, AA (400, 600 or 800 mg/kg, intraperitoneally)-induced mortality and hepatotoxicity were significantly decreased by MLT (10 mg/kg, subcutaneously). Pretreatment with...Continue Reading

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Dec 25, 2010·World Journal of Gastroenterology : WJG·Alexander M Mathes
Jan 2, 2009·International Urology and Nephrology·Yusuf Ozlem IlbeyFatih Mete
Sep 2, 2008·Biological & Pharmaceutical Bulletin·Ayantika Ghosh, Parames Chandra Sil
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