LIPID-PEROXIDATION OF RAT MYOCARDIAL TISSUE FOLLOWING DAUNOMYCIN ADMINISTRATION

Daunomycin-induced cardiotoxicity has been regarded to be the result o f oxygen-mediated lipid peroxidation of cell membranes. The aim of the present work was to evaluate the extent of lipid peroxidation in rat heart after administration of this anticancer drug and, further, to ex amine possible activation of some endogenous antioxidant defense syste ms. Myocardial tissue from both control and drug-treated rats was test ed for lipid peroxidation using a selective third-order derivative met hod that is based on the analysis of the free malondialdehyde produced . Determination of reduced/oxidized glutathione levels and measurement of the activity of DT-diaphorase, glutathione-S-transferase, glutathi one reductase, glucose-6-phosphate dehydrogenase and NADPH-cytochrome P-450 reductase were also carried out using literature methods. Signif icant increase of malondialdehyde content, and DT-diaphorase and gluta thione-S-transferase activities were found in myocardial tissue from d aunomycin-treated rats. On the other hand, reduced and oxidized glutat hione levels were significantly decreased while the activity of glutat hione reductase, glucose-6-phosphate dehydrogenase and NADPH-cytochrom e P-450 reductase remained unchanged after daunomycin administration. The results of the present study give further evidence that daunomycin can induce lipid peroxidation in heart. However, additional experimen tation is needed in order to delineate the molecular details of this p rocess as well as of the mechanisms evolved to limit it. (C) 1998 Else vier Science Ireland Ltd. All rights reserved.