Gallagher E P, Kedderis G L, Di Giulio R T
Ecotoxicology Laboratory, School of Forestry and Environmental Studies, Duke University, Durham, NC 27706.
Biochem Pharmacol. 1991 Jun 21;42(1):139-45. doi: 10.1016/0006-2952(91)90692-x.
Chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile) is a broad spectrum fungicide that is a potent acute toxicant to fish. Therefore, the metabolism of chlorothalonil was investigated in liver and gill cytosolic and microsomal fractions from channel catfish (Ictalurus punctatus) using HPLC. All fractions catalyzed the metabolism of chlorothalonil to polar metabolites. Chlorothalonil metabolism by cytosolic fractions was reduced markedly when glutathione (GSH) was omitted from the reaction mixtures. The lack of microsomal metabolism in the presence of either NADPH or an NADPH-regenerating system indicated direct glutathione S-transferase (GST)-catalyzed conjugation with GSH without prior oxidation by cytochrome P450. Cytosolic and microsomal GSTs from both tissues were also active toward 1-chloro-2,4-dinitrobenzene (CDNB), a commonly employed reference substrate. In summary, channel catfish detoxified chlorothalonil in vitro by GST-catalyzed GSH conjugation in the liver and gill. The present report is the first to confirm microsomal GST activity toward CDNB in gill and toward chlorothalonil in liver, and also of gill cytosolic GST activity towards chlorothalonil, in an aquatic species.
百菌清（2,4,5,6-四氯间苯二腈）是一种广谱杀菌剂，对鱼类具有很强的急性毒性。因此，利用高效液相色谱法研究了斑点叉尾鮰肝脏和鳃的胞质溶胶及微粒体部分中百菌清的代谢情况。所有部分均催化百菌清代谢为极性代谢产物。当反应混合物中省略谷胱甘肽（GSH）时，胞质溶胶部分对百菌清的代谢显著降低。在存在烟酰胺腺嘌呤二核苷酸磷酸（NADPH）或NADPH再生系统的情况下微粒体缺乏代谢，这表明是直接由谷胱甘肽S-转移酶（GST）催化与GSH结合，而无需细胞色素P450预先氧化。来自这两种组织的胞质溶胶和微粒体GST对常用的参考底物1-氯-2,4-二硝基苯（CDNB）也有活性。总之，斑点叉尾鮰在体外通过肝脏和鳃中GST催化的GSH结合作用对百菌清进行解毒。本报告首次证实了在一个水生物种中，微粒体GST对鳃中的CDNB以及对肝脏中的百菌清具有活性，同时也证实了鳃胞质溶胶GST对百菌清具有活性。
