Xanthine oxidase mediates paraquat-induced toxicity on cultured endothelial cell.
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.
Sakai
M
M
Department of Emergency & Critical Care Medicine, Kansai Medical University, Osaka, Japan.
Yamagami
K
K
Kitazawa
Y
Y
Takeyama
N
N
Tanaka
T
T
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000293:injuries; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006540:Herbicides / Q000506:poisoning*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010269:Paraquat / Q000506:poisoning*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013482:Superoxide Dismutase / Q000494:pharmacology; D014414:Tungsten / Q000494:pharmacology; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism*
D004791:Enzyme Inhibitors; D006540:Herbicides; D000493:Allopurinol; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D010269:Paraquat; D010100:Oxygen; D014414:Tungsten