Melatonin Protects on Toxicity by Acetaminophen But Not on Pharmacological Effects in Mice(Pharmacology)

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概要

• 論文の詳細を見る

• 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 (100μM) had a significant protective effect on the AA (7mM)-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 6h and was followed by an increase in lipid peroxidation at 12h in hepatocytes. MLT (0.1, 1, 10 or 100μM) 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, intraperitonealy)-induced mortality and hepatotoxicity were significantly decreased by MLT (10 mg/kg, subcutaneously). Pretreatment with MLT had a greater protective effect on the hepatotoxicity of AA than post-treatment. However, MLT had no protective effect on the antipyretic effect or antinociception caused by AA. These results suggest that MLT is potentially useful for preventing AA-induced toxicity, but not the antipyretic effect or antinociception caused by AA.

• 公益社団法人日本薬学会の論文
• 2006-03-01

著者

• ISHIKAWA Masaaki

  Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi

• KANNO Syu-ichi

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• KITAJIMA Yasue

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• KAKUTA Mai

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• OSANAI Yuu

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• UJIBE Mayuko

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• Kakuta Mai

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

• Osanai Yuu

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

• Ujibe Mayuko

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

• Kanno Syu-ichi

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

• Kanno Syu-ichi

  東北薬科大学癌研究所

• Kimura Katsuhiko

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

• Kitajima Yasue

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

• Kanno Syu-ichi

  東北薬科大学 薬物治療学教室

• OHTAKE Takaharu

  Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University

• KOIWAI Kimiko

  Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku College of Pharmacy

• Kanno Syu-ichi

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• TOMIZAWA Ayako

  Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi

• HIURA Takako

  Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi

• OHTAKE Takaharu

  Tohoku Employee's Pension Welfare Hospital

• Ishikawa Masaaki

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

• Ishikawa Masaaki

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Ishikawa Masaaki

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku College Of Pharmacy

• Hiura Takako

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

• Koiwai Kimiko

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Tomizawa Ayako

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Ohtake Takaharu

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

• Ishikawa Masaaki

  Dep. Of Clinical Pharmacotheraputics Tohoku Pharmaceutical Univ. Jpn

• Koiwai Kimiko

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

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