Vitarius J A, O'Shaughnessy J A, Sultatos L G
Department of Pharmacology and Toxicology, New Jersey Medical School, Newark 07103, USA.
Pharmacol Toxicol. 1995 Jul;77(1):16-22. doi: 10.1111/j.1600-0773.1995.tb01908.x.
The effects of induction of various forms of cytochromes P450 by chemicals like phenobarbital on the hepatic oxidative desulfuration and acute toxicity of the phosphorothioate insecticide parathion have been well-characterized. However, the effects of these chemicals on the metabolism and acute toxicity of the active metabolite paraoxon are less understood. In the present study, daily pretreatment of mice with phenobarbital (intraperitoneally 75 mg/kg) for up to eight days resulted in a transient increase in hepatic microsomal A-esterase activity, with a corresponding transient decrease in serum A-esterase activity (A-esterase was defined as hydrolysis of paraoxon which could be inhibited by EDTA). These alterations could be accounted for by a temporary decrease in the rate of secretion of A-esterase from liver. However, the same pretreatment resulted in a sustained protective effect against the acute toxicity of paraoxon. These data suggest that alterations in A-esterase activity as a result of phenobarbital pretreatment cannot account for the observed antagonism of the acute toxicity of paraoxon. Furthermore, these data demonstrate that the protective effect of phenobarbital pretreatment on phosphorothioate insecticides like parathion cannot be attributed exclusively to alterations in oxidative desulfuration of these compounds.
像苯巴比妥这样的化学物质诱导各种形式的细胞色素P450对肝脏氧化脱硫作用以及对硫磷杀虫剂对硫磷急性毒性的影响已得到充分表征。然而，这些化学物质对活性代谢物对氧磷的代谢和急性毒性的影响了解较少。在本研究中，给小鼠每日腹腔注射75 mg/kg苯巴比妥预处理长达8天，导致肝脏微粒体A酯酶活性短暂增加，同时血清A酯酶活性相应短暂降低（A酯酶定义为可被EDTA抑制的对氧磷水解）。这些改变可由肝脏A酯酶分泌速率暂时降低来解释。然而，相同的预处理对氧磷急性毒性产生了持续的保护作用。这些数据表明，苯巴比妥预处理导致的A酯酶活性改变不能解释所观察到的对氧磷急性毒性的拮抗作用。此外，这些数据表明，苯巴比妥预处理对硫代磷酸酯类杀虫剂如对硫磷的保护作用不能完全归因于这些化合物氧化脱硫的改变。
