Action of reactive oxygen species and their antagonists on twitch tension of the rat phrenic nerve-diaphragm.
Reactive oxygen species have been implicated in normal and pathological processes of many tissues, including skeletal muscle. I extended previous studies by examining the effect of these intermediates and eight of their antagonists (superoxide dismutase, catalase, deferoxamine, [Cu(II)]2(3,5-diisopropylsalicylate)4, 1,2-dimethyl-3-hydroxy-pyridone, 1,3-dimethyl-2-thiourea, N-(2-mercaptopropionyl)-glycine, vitamin E) on indirectly stimulated twitch tension of an in vitro neuroskeletomuscular preparation, the phrenic nerve-diaphragm of the rat. In the absence of exogenous reactive oxygen species, none of the antagonists potentiated twitch tension, and all but one (N-[2-mercaptopropionyl]-glycine) of the membrane-permeant antagonists attenuated twitch tension. The reactive oxygen intermediate-generating system of purine plus xanthine oxidase reduced indirectly stimulated twitch tension by 36% while having no effect on directly stimulated twitch tension. Catalase (but not superoxide dismutase or deferoxamine) eliminated the reduction in twitch tension, indicating that hydrogen peroxide played a role in the reduction. The membrane-permeant antagonists [Cu(II)]2(3,5-diisopropylsalicylate)4 and 1,2-dimethyl-3-hydroxy-pyridone also eliminated the reduction in twitch tension caused by reactive oxygen species, suggesting that hydrogen peroxide could have acted intracellularly through an iron-catalyzed Haber-Weiss reaction to produce hydroxyl radical, which in turn reacted with intracellular components, thereby reducing twitch tension.
Crosland
R D
RD
Toxinology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702-5011, USA.
D000704:Analysis of Variance; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects* / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D010791:Phrenic Nerve / Q000187:drug effects* / Q000502:physiology; D011728:Pyridones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D008625:Tiopronin / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D011728:Pyridones; D017382:Reactive Oxygen Species; D014810:Vitamin E; D000077543:Deferiprone; C038983:1,3-dimethylthiourea; D008625:Tiopronin; D002374:Catalase; D013482:Superoxide Dismutase; D013890:Thiourea; D003676:Deferoxamine