Cocaine-induced liver injury in mice is mediated by nitric oxide and reactive oxygen species

被引:53
作者
Aoki, K [1 ]
Ohmori, M [1 ]
Takimoto, M [1 ]
Ota, H [1 ]
Yoshida, T [1 ]
机构
[1] SHOWA UNIV,SCH MED,DEPT PATHOL 2,SHINAGAWA KU,TOKYO 142,JAPAN
关键词
cocaine; hepatotoxicity; nitric oxide (NO); reactive oxygen species; (mouse);
D O I
10.1016/S0014-2999(97)01230-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 injection of cocaine in adult male ICR mice. Pretreatment with aminoguanidine (an inhibitor of NO synthase), N-methyl-D-glucamine dithiocarbamate complex with iron ion (II) (Fe2+(MGD)(2), a trapping reagent of NO) or deferoxamine complex with iron ion (III) (Fe3+-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 (O-2(-)) via peroxynitrite may be involved in the pathogenesis of cocaine hepatotoxicity. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:43 / 49
页数:7
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