title: Antioxidants protect rat diaphragmatic muscle function under hypoxic conditions.
abstract: In hypoxia, mitochondrial respiration is decreased, thereby leading to a buildup of reducing equivalents that cannot be transferred to O2 at the cytochrome oxidase. This condition, called reductive stress, can paradoxically lead to enhanced formation of reactive O2 species, or a decrease in the ability of the cell to defend against an oxidative stress. We hypothesized that antioxidants would protect tissues under conditions of hypoxia. Rat diaphragm strips were incubated in tissue baths containing one of four antioxidants: N-acetyl-L-cysteine, dimethyl sulfoxide, superoxide dismutase, or Tiron. The strips were directly stimulated in an electrical field. Force-frequency relationships were studied under baseline oxygenation (95% O2-5% CO2), after 30 min of hypoxia (95% N2-5% CO2), and 30 min after reoxygenation. In all tissues, antioxidants markedly attenuated the loss of contractile function during hypoxia (P < 0.01) and also significantly improved recovery on reoxygenation (P < 0.05). We conclude that both intracellular and extracellular antioxidants improve skeletal muscle contractile function in hypoxia and facilitate recovery during reoxygenation in an in vitro system. The strong influence of antioxidants during hypoxic exposure suggests that they can be as effective in protecting cell function in a reducing environment as they have been in oxidizing environments.
authors.affiliation: Department of Physiology, Pulmonary and Critical Care Division, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: P
authors.initials: P
authors.lastname: Mohanraj
authors.forename: A J
authors.initials: AJ
authors.lastname: Merola
authors.forename: V P
authors.initials: VP
authors.lastname: Wright
authors.forename: T L
authors.initials: TL
authors.lastname: Clanton
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004558:Electric Stimulation; D016166:Free Radical Scavengers / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012132:Respiratory Muscles / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D013482:Superoxide Dismutase; D000111:Acetylcysteine; D004121:Dimethyl Sulfoxide