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 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.
Ohtaka
K
K
Department of Anaesthesiology, Akita University School of Medicine, Japan.
Koizumi
A
A
D000818:Animals; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D063086:Organothiophosphates / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism*
D005609:Free Radicals; D063086:Organothiophosphates; C023890:O,O,O-trimethyl phosphorothioate; C019123:O,O,S-trimethyl phosphorothioate; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase