Ohtaka K, Koizumi A
Department of Anaesthesiology, Akita University School of Medicine, Japan.
Pharmacol Toxicol. 1994 Sep-Oct;75(3-4):206-11. doi: 10.1111/j.1600-0773.1994.tb00348.x.
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.
本研究旨在探讨脂质过氧化作用以及一种典型的自由基生成酶——黄嘌呤氧化酶在硫代磷酸O,O,S-三甲酯（OOS-TMP）所致肺损伤中的作用。将动物（每组5只）按40mg/kg的剂量给予OOS-TMP，并在处理后的第1、3或7天处死。在第1天，OOS-TMP使肺中的脂质过氧化（平均值±标准误）增加至对照值的139±9.6%，肝脏中的脂质过氧化增加至对照值的623±203%。当大鼠按20、40和60mg/kg的剂量给予OOS-TMP时，肺和肝脏中的脂质过氧化呈剂量依赖性增加。在肺中，黄嘌呤氧化酶的总活性同时增加。相比之下，超氧化物歧化酶和过氧化氢酶的活性未受影响。与无毒剂量（1mg/kg）的硫代磷酸O,O,O-三甲酯共同给药可完全消除OOS-TMP对脂质过氧化和黄嘌呤氧化酶总活性的影响，硫代磷酸O,O,O-三甲酯可拮抗OOS-TMP处理后的肺损伤。目前的结果表明，自由基形成可能通过激活黄嘌呤氧化酶等自由基生成酶参与OOS-TMP处理后的肺损伤。
