Sultatos L G
Toxicol Appl Pharmacol. 1986 Oct;86(1):105-11. doi: 10.1016/0041-008x(86)90403-5.
Single-pass perfusion of mouse livers in situ with the phosphorothioate pesticide parathion resulted in formation of the cholinesterase inhibitor paraoxon (PO), p-nitrophenol (PNP), p-nitrophenyl sulfate (PNPS), and p-nitrophenyl glucuronide (PNPG). Daily pretreatment of mice with phenobarbital (80 mg/kg, ip) for 4 days induced hepatic cytochrome P-450 content, as well as oxidative activation and oxidative detoxification of parathion, as measured in vitro. However, phenobarbital pretreatment did not alter production of PO from parathion in mouse livers perfused in situ, although it increased production of PNP, PNPS, and PNPG. Additionally, phenobarbital pretreatment antagonized the acute toxicity of parathion in mice. These results indicate that phenobarbital pretreatment clearly induces that form(s) of cytochrome P-450 catalyzing conversion of parathion to PO. Yet increased amounts of PO do not exit perfused livers from phenobarbital pretreated mice. Instead, the enhanced detoxification of parathion to PNP, PNPS, and PNPG likely results in the observed antagonism of parathion's acute toxicity.
用硫代磷酸酯农药对硫磷对小鼠肝脏进行原位单次灌注，会导致胆碱酯酶抑制剂对氧磷（PO）、对硝基苯酚（PNP）、对硝基苯硫酸酯（PNPS）和对硝基苯葡萄糖醛酸酯（PNPG）的形成。每天用苯巴比妥（80毫克/千克，腹腔注射）对小鼠进行预处理，持续4天，可诱导肝脏细胞色素P - 450含量增加，以及对硫磷的氧化活化和氧化解毒，这是在体外测量的结果。然而，苯巴比妥预处理并没有改变原位灌注的小鼠肝脏中对硫磷生成PO的情况，尽管它增加了PNP、PNPS和PNPG的生成。此外，苯巴比妥预处理可拮抗对硫磷对小鼠的急性毒性。这些结果表明，苯巴比妥预处理明显诱导了催化对硫磷转化为PO的细胞色素P - 450形式。然而，苯巴比妥预处理的小鼠的灌注肝脏中并没有产生更多的PO。相反，对硫磷向PNP、PNPS和PNPG的解毒增强可能导致了观察到的对硫磷急性毒性的拮抗作用。
