title: Indomethacin ameliorates trimethyltin-induced neuronal damage in vivo by attenuating oxidative stress in the dentate gyrus of mice.
abstract: 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.
authors: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573–0101, Japan.
authors: Nguyen Quynh
authors: NQ
authors: Huong
authors: Yukary
authors: Y
authors: Nakamura
authors: Nobuyuki
authors: N
authors: Kuramoto
authors: Masanori
authors: M
authors: Yoneyama
authors: Reiko
authors: R
authors: Nagashima
authors: Tatsuo
authors: T
authors: Shiba
authors: Taro
authors: T
authors: Yamaguchi
authors: Shigeru
authors: S
authors: Hasebe
authors: Kiyokazu
authors: K
authors: Ogita
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014298:Trimethyltin Compounds / Q000633:toxicity
chemical_list: D000447:Aldehydes; D016861:Cyclooxygenase Inhibitors; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D014298:Trimethyltin Compounds; C040533:trimethyltin chloride; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D053148:Caspase 3; C027576:4-hydroxy-2-nonenal; D007213:Indomethacin