Indomethacin Ameliorates Trimethyltin-Induced Neuronal Damage in Vivo by Attenuating Oxidative Stress in the Dentate Gyrus of Mice
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概要
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The organotin trimethyltin (TMT) is well known to cause neuronal degeneration in the hippocampal dentate gyrus of mice. The first purpose of the present study was to examine whether the cyclooxygenase (COX) inhibitor indomethacin could ameliorate neuronal degeneration in the dentate gyrus of mice following TMT treatment in vivo. The systemic injection into mice of TMT at 2.8 mg/kg produced activation of endogenous caspase-3 and calpain, enhanced the gene expression of COX-1 and COX-2, activated microglial cells, and caused the formation of the lipid peroxidation product 4-hydroxynonenal in the hippocampus. Given at 12-h post-TMT treatment, the systemic injection of indomethacin (5 or 10 mg/kg, subcutaneously) significantly decreased the TMT-induced damage to neurons having active caspase-3 and single-stranded DNA in the dentate granule cell layer of the hippocampus. The results of the α-Fodrin degradation test revealed that the post-treatment with indomethacin was effective in attenuating TMT-induced activation of endogenous caspases and calpain in the hippocampus. In TMT-treated animals, interestingly, the post-treatment with indomethacin produced not only activation of microglial cells in the dentate gyrus but also the formation of 4-hydroxynonenal in the dentate granule cell layer. Taken together, our data suggest that COX inhibition by indomethacin ameliorated TMT-induced neuronal degeneration in the dentate gyrus by attenuating intensive oxidative stress.
- 公益社団法人 日本薬学会の論文
著者
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Ogita Kiyokazu
Department Of Parmacology Setsunan University
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Yoneyama Masanori
Department Of Pharmacology Setsunan University Faculty Of Pharmaceutical Sciences
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Kuramoto Nobuyuki
Department Of Pharmacology Setsunan University
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Huong Nguyen
Department Of Bioproduction And Environmental Science Faculty Of Agriculture Kyushu University
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Shiba Tatsuo
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Setsunan University
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Nagashima Reiko
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Setsunan University
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Hasebe Shigeru
Department Of Pharmacology Setsunan University Faculty Of Pharmaceutical Sciences
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Yamaguchi Taro
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Setsunan University
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Huong Nguyen
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
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NAKAMURA Yukary
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
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Ogita Kiyokazu
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
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Yoneyama Masanori
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
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Shiba Tatsuo
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
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Kuramoto Nobuyuki
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
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