LIPID PEROXIDATION AND ANTIOXIDANT ACTION OF A-TOCOPHEROL OF NEONATAL CARDIAC RAT CELLS IN CULTURE AFTER DAUNOMYCIN ADMINISTRATION
Abstract
Daunomycin (DNM) is an anthracycline with a high antineoplasmatic acrion which is toxic to cardiac cells. The topicity of DNM is attributed to its enzyme reduction to semiquinones with a concomittant production of OFRs. The aim of this study was to investigate the toxic effect of DNM in culture of neonatal beating cardiac rat cells (in vitro) and investigate the possible protective role of DT-diaphorase, glutathione-S-transferase (GST) from OFRs. Initially, we isolated and purified cardiac cells from 3 day old Wistar rats. Then, we investigated the toxic effects of DNM in νarίοus concestrations, measuring the lactate dehydrogenase (LDH) activity that was released in the medium from the cardiac cells. We evaluated the toxic effect of DNM in various concentrations measuring the LDH activity on the medium, evaluating the a-tocopherol effect. We also measured the specific activities of DT-diaphorase and GST after DNM and a-tocopherol administration. Following administration of 10μΜ a-tocopherol, we noticed a maximum LDH activity in a 10μg/ml DNM concentration on the second day. Co administration of 100μΜ a-tocopherol showed a decrease in LDH activity of 47%. The specific activities of DT-diaphorase and GST showed an induction of 107% and 90% respectively, after incubation with 0.2μg/ml DNM. This is an indication that these enzymes take part in the DNM metabolism. Cell incubation with a-tocopherol and co-administration of 0.2μg/ml DNM resulted to a decrease of 48% the specific activity of DT diaphorase and 30% of GST, on the second day. The findings of this study have shown in vitro DNM lipid peroxidation, something evident from DT-diaphorase and GST induction. A-tocopherol has significantly decreased this induction proving its protective role on the cardiac cells. In the future, the cardiotoxic effects of anthracyclines may be decreased with clinical use οf various antioxidant substances, such as a-tocopherol.References
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