Sakai M, Yamagami K, Kitazawa Y, Takeyama N, Tanaka T
Department of Emergency & Critical Care Medicine, Kansai Medical University, Osaka, Japan.
Pharmacol Toxicol. 1995 Jul;77(1):36-40. doi: 10.1111/j.1600-0773.1995.tb01911.x.
The role of xanthine oxidase in paraquat toxicity was investigated using cultured bovine pulmonary artery endothelial cells. Exposure to paraquat 0.1 mM was done for 24 hr with or without tungsten pretreatment and in the presence or absence of xanthine oxidase inhibitors. Exposure to paraquat significantly increased O2- production and relative xanthine oxidase activity (xanthine oxidase activity divided by total xanthine dehydrogenase plus xanthine oxidase) while depressing cell growth. In contrast, tungsten and allopurinol inhibited the increase of xanthine oxidase activity and decreased O2- release. Cell injury was assessed by leakage of lactate dehydrogenase and by fluorescein diacetate staining; it was found that oxidase inhibitors (both allopurinol and tungsten) reduced paraquat cytotoxicity. Thus the toxicity of paraquat was at least partly due to intracellular O2- production mediated by xanthine oxidase and the subsequent formation of other free radicals.
使用培养的牛肺动脉内皮细胞研究了黄嘌呤氧化酶在百草枯毒性中的作用。在有或没有钨预处理以及有或没有黄嘌呤氧化酶抑制剂存在的情况下，将细胞暴露于0.1 mM百草枯中24小时。暴露于百草枯会显著增加超氧阴离子（O2-）的产生和相对黄嘌呤氧化酶活性（黄嘌呤氧化酶活性除以总黄嘌呤脱氢酶加黄嘌呤氧化酶），同时抑制细胞生长。相比之下，钨和别嘌呤醇抑制了黄嘌呤氧化酶活性的增加并减少了超氧阴离子（O2-）的释放。通过乳酸脱氢酶泄漏和荧光素二乙酸酯染色评估细胞损伤；发现氧化酶抑制剂（别嘌呤醇和钨）均降低了百草枯的细胞毒性。因此，百草枯的毒性至少部分归因于黄嘌呤氧化酶介导的细胞内超氧阴离子（O2-）产生以及随后其他自由基的形成。
