ENHANCED LEVELS OF LIPID-PEROXIDATION AND XANTHINE-OXIDASE ACTIVITY IN THE LUNG OF MALE SPRAGUE-DAWLEY RATS FOLLOWING TREATMENT WITH O,O,S-TRIMETHYL PHOSPHOROTHIOATE

The purpose of this study was to investigate the roles of lipid peroxi dation and a prototypical radical generating enzyme, xanthine oxidase, in lung injury caused by O,O,S-trimethyl phosphorothioate (OOS-TMP). Animals (five per group) were dosed with OOS-TMP at 40 mg/kg and sacri ficed on the 1st, 3rd or 7th day after treatment. OOS-TMP increased li pid peroxidation (Mean+/-S.E.) to 139+/-9.6% of the control values in the lung and to 623 +/- 203% in the liver on the 1st day. When rats we re dosed with OOS-TMP at 20, 40 and 60 mg/kg, lipid peroxidation in th e lung and the liver were increased in a dose-dependent manner. In the lung, the total activity of xanthine oxidase was coincidentally incre ased. In contrast, the activities of superoxide dismutase and catalase were not affected. Effects of OOS-TMP on lipid peroxidation and the t otal activity of xanthine oxidase were completely abolished by coadmin istration with O,O,O-trimethyl phosphorothionate of a non-toxic dose ( 1 mg/kg), which antagonizes the lung injury after treatment with OOSTM P. The present results indicate that free radical formation may be inv olved in lung injury after OOS-TMP treatment through activation of rad ical producing enzymes such as xanthine oxidase.