Cardiotoxic effects of nitrofurantoin and tertiary butylhydroperoxide in vitro: are oxygen radicals involved?
Langendorff rat hearts were perfused for 15, 30 or 75 min. with the oxygen radical generators nitrofurantoin (0.25 or 0.5 mmol/l) or tertiary butylhydroperoxide (0.25 mmol/l). Both agents reduced the force of contraction and increased the release of glutathione, oxidized glutathione, lactate dehydrogenase and creatine phosphokinase into the perfusion fluid. The tissue concentration of glutathione was reduced. While there were no signs of an increased production of conjugated dienes, the tissue concentration of malondialdehyde was greater than in control experiments. The variability of the latter effect was large, however, and in most cases the increase was not statistically significant. Addition of catalase (100 mU/ml) or catechin (0.5 mmol/l) to the perfusion medium abolished the nitrofurantoin induced release of oxidized glutathione but did not not prevent or attenuate enzyme leakage from the cells and the development of a negative inotropic effect. These results suggest that the cardiotoxic effects of nitrofurantoin and tertiary butylhydroperoxide cannot be explained by the appearance of oxygen radicals alone and that an increased lipid peroxidation is not the mechanism which is primarily responsible for cell death.
Biel
B
B
Institute of Pharmacology, Medical University of Lübeck, Germany.
Younes
M
M
Brasch
H
H
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002392:Catechin / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D003864:Depression, Chemical; D005609:Free Radicals; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D006321:Heart / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009582:Nitrofurantoin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010100:Oxygen / Q000378:metabolism*; D010477:Perfusion; D010545:Peroxides / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D020122:tert-Butylhydroperoxide
D005609:Free Radicals; D010545:Peroxides; D002392:Catechin; D009582:Nitrofurantoin; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D003402:Creatine Kinase; D005978:Glutathione; D010100:Oxygen; D019803:Glutathione Disulfide