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

Abstract

The purpose of this study was to investigate the roles of lipid peroxidation 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 sacrificed on the 1st, 3rd or 7th day after treatment. OOS-TMP increased lipid 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 were dosed with OOS-TMP at 20, 40 and 60 mg/kg, lipid peroxidation in the lung and the liver were increased in a dose-dependent manner. In the lung, the total activity of xanthine oxidase was coincidentally increased. In contrast, the activities of superoxide dismutase and catalase were not affected. Effects of OOS-TMP on lipid peroxidation and the total activity of xanthine oxidase were completely abolished by coadministration with O,O,O-trimethyl phosphorothionate of a non-toxic dose (1 mg/kg), which antagonizes the lung injury after treatment with OOS-TMP. The present results indicate that free radical formation may be involved in lung injury after OOS-TMP treatment through activation of radical producing enzymes such as xanthine oxidase.

S-Methylation of O,O-Dialkyl Phosphorodithioic Acids: O,O,S-Trimethyl Phosphorodithioate and Phosphorothiolate as Metabolites of Dimethoate in Mice

“…(MeO) 2 P(S)SMe and (MeO) 2 P(O)SMe are poor inhibitors of cholinesterase (4, 5) and poor alkylating agents (23,24). Several studies have focused on the lung as a primary site of toxicity for (MeO) 2 P(O)SMe (7,8,(25)(26)(27). (MeO) 2 P(S)SMe is not a lung-specific toxin, and when administered to rats in small amounts, it prevents the lung damage caused by analogs of (MeO) 2 P(O)SMe (8,28).…”