Phorbol ester cardiotoxicity: are .O2-radicals involved?
The effect of superoxide dismutase (SOD) on cardiotoxic effects induced by phorbol 12-myristate 13-acetate (PMA) was investigated in isolated perfused rat hearts. The negative inotropic effect, vasoconstriction, and mild bradycardia were uneffected by SOD in the perfusion medium. Perfusion of Langendorff hearts with PMA and oxidized cytochrome c +/- SOD gave no evidence for a formation of .O2 radicals in response to PMA. Cytochrome c reduction detected in the perfusate of PMA-treated Langendorff hearts is not inhibited by SOD and has thus to be attributed to .O2-independent myocardial reducing systems.
Esser
E
E
Grünenthal GmbH, Center of Research, Aachen.
Loschen
G
G
Flohé
L
L
D000818:Animals; D003574:Cytochrome c Group / Q000378:metabolism; D005609:Free Radicals; D006321:Heart / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen; D010477:Perfusion; D010703:Phorbol Esters / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000633:toxicity*
D003574:Cytochrome c Group; D005609:Free Radicals; D010703:Phorbol Esters; D013481:Superoxides; D013482:Superoxide Dismutase; D010100:Oxygen