Aoki K, Ohmori M, Takimoto M, Ota H, Yoshida T
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Eur J Pharmacol. 1997 Oct 1;336(1):43-9. doi: 10.1016/s0014-2999(97)01230-2.
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 (O2-) via peroxynitrite may be involved in the pathogenesis of cocaine hepatotoxicity.
通过测量血浆丙氨酸转氨酶活性并进行组织学研究，考察了一氧化氮（NO）和活性氧对可卡因诱导的肝毒性的调节作用。成年雄性ICR小鼠单次注射可卡因诱导肝损伤。用氨基胍（一种一氧化氮合酶抑制剂）、N-甲基-D-葡糖胺二硫代氨基甲酸盐与铁离子（II）的络合物（Fe2+(MGD)2，一种一氧化氮捕获剂）或去铁胺与铁离子（III）的络合物（Fe3+-去铁胺，一种一氧化氮清除剂）预处理，可显著抑制可卡因诱导的肝毒性。此外，用别嘌呤醇（一种黄嘌呤氧化酶抑制剂）和1,3-二甲基硫脲（一种羟自由基清除剂）预处理也可产生强效抑制作用。这些发现表明，NO与超氧阴离子（O2-）通过过氧亚硝酸盐反应产生的羟自由基可能参与了可卡因肝毒性的发病机制。
