Some characteristics of hydrogen- and alkylhydroperoxides metabolizing systems in cardiac tissue.
The effect of hydroperoxides on the cardiac tissue was studied by using hemoglobin-free perfused rat heart. Ethylhydroperoxide was degraded mainly through the glutathione peroxidase system of the heart at a maximal rate of about 1.2 mumol/min per g wet wt. When ethylhydroperoxide infused was not degraded completely, the hydroperoxide concentration in the effluent perfusate paralleled the formation of ferrylmyoglobin in the heart. The infusion of ethylhydroperoxide caused release of oxidized glutathione into the effluent perfusate as a result of the enhancement of the cytosolic glutathione peroxidase reaction. The leakage of oxidized glutathione reached the maximal rate of 3.5 nmol/min per g wet wt with the infusion of 175 microM ethylhydroperoxide. At hydroperoxide concentrations above 150 microM, oxidations of pyridine nucleotides and of cytochrome a + a3 occurred, probably through a stimulation of the mitochondrial glutathione peroxidase reaction, and resulted in sudden failure of the heart function. The infusion of t-butyl- and cumene-hydroperoxides, which are unable to react with myoglobin, also caused the oxidations of pyridine nucleotides and cytochrome a + a3, the inhibition of oxygen consumption and the failure of heart function. The results indicate that the cardiac toxicity of hydroperoxides is due mainly to their effect on mitochondrial metabolism.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D017936:Cytochrome a Group; D003580:Cytochromes / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006334:Heart Function Tests; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010477:Perfusion; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D017936:Cytochrome a Group; D003580:Cytochromes; D009211:Myoglobin; D010545:Peroxides; D009249:NADP; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase