毒理学相关资料,第五章内容参考文献18.pdfVIP

European Journal of Pharmacology 336 1997 43–49 Cocaine-induced liver injury in mice is mediated by nitric oxide and reactive oxygen species Kimiko Aoki a, , Mitsuyo Ohmori a , Masafumi Takimoto b , Hidekazu Ota b , Takemi Yoshida a a Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa Uniersity, Shinagawa-ku, 1-5-8 Hatanodai, Tokyo 142, Japan b 2nd Department of Pathology, School of Medicine, Showa Uniersity, Shinagawa-ku, 1-5-8 Hatanodai, Tokyo 142, Japan Received 17 April 1997; revised 28 July 1997; accepted 1 August 1997 Abstract The modulating effects of nitric oxide NO and reactive oxygen species on cocaine-induced hepatotoxicity were examined by measuring plasma alanine aminotransferase activity and by carrying out histological studies. Liver injury was induced by a single D-glucamine injection of cocaine in adult male ICR mice. Pretreatment with aminoguanidine an inhibitor of NO synthase , N-methyl- dithiocarbamate complex with iron ion II Fe2 MGD2 , a trapping reagent of NO or deferoxamine complex with iron ion III 3 Fe -deferoxamine, a scavenger of NO produced a marked inhibition of the hepatotoxicity induced by cocaine. In addition, pretreatment with allopurinol an inhibitor of xanthine oxidase and 1,3-dimethylthiourea a scavenger of hydroxyl radical also produced a potent inhibition. These findings suggest that a hydroxyl radical produced by the reaction of NO and superoxide anion O2 via peroxynitrite may be involved