Lipid peroxidation and changes in cytochrome c oxidase and xanthine oxidase activity in organophosphorus anticholinesterase induced myopathy.
A possible role of radical oxygen species (ROS) initiated lipid peroxidation in diisopropylphosphorofluoridate (DFP)-induced muscle necrosis was investigated by quantifying muscle changes in F2-isoprostanes, novel and extremely accurate markers of lipid peroxidation in vivo. A significant increase in F2-isoprostanes of 56% was found in the diaphragm of rats 60 min after DFP-induced fasciculations. As possible source of ROS initiating lipid peroxidation, the cytocrome-c oxidase (Cyt-ox) and xanthine dehydrogenase-xanthine oxidase (XD-XO) systems were investigated. Within 30 min of onset of fasciculations Cyt-ox activity was reduced by 50% from 0.526 to 0.263 mumol/mg prot/min and XO activity increased from 0.242 to 0.541 mumol/mg prot/min. Total XD-XO activity was unchanged, indicating a conversion from XD into XO. In rats pretreatment with the neuromuscular blocking agent d-tubocurarine, prevented DFP-induced fasciculations, increases in F2-isoprostanes and changes in Cyt-ox or XD-XO. The decrease in Cyt-ox and increase in XO suggest that ROS are produced during DFP induced muscle fasciculations initiating lipid peroxidation and subsequent myopathy.
Yang
Z P
ZP
Department of Pharmacology and Neurology, Vanderbilt University, School of Medicine, Nashville, TN 37212, USA.
Dettbarn
W D
WD
D000818:Animals; D003576:Electron Transport Complex IV / Q000378:metabolism*; D007531:Isoflurophate / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D009135:Muscular Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D003473:Neuromuscular Nondepolarizing Agents / Q000633:toxicity; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014403:Tubocurarine / Q000633:toxicity; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism*
D003473:Neuromuscular Nondepolarizing Agents; D017382:Reactive Oxygen Species; D007531:Isoflurophate; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D003576:Electron Transport Complex IV; D014403:Tubocurarine