PROTECTIVE ROLE OF ANTIOXIDANT VITAMINS ON ADRIAMYCIN-INDUCED FREE-RADICAL PRODUCTION AND CARDIOTOXICITY IN GUINEA-PIGS

Guinea pigs were divided into three groups: control, adriamycin and ad riamycin plus vitamin groups, and treated with physiological saline so lution (control group), adriamycin (adriamycin group) and adriamycin p lus vitamins E and C (adriamycin plus vitamin group). Activities of su peroxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) and concentrations of malondialdehyde (MDA), conjugated dienes (CD), hydroxyl radical (OH.) and iron were measured in heart and liver tissues of all animals. Electron microscopic analysis and free radica l concentrations of all tissues were also carried out. In the heart ti ssues, activities of SOD and GSH-Px enzymes decreased and that of CAT unchanged in adriamycin and vitamin plus groups relative to control va lues. MDA, OH., CD and iron levels were higher in the heart tissues of adriamycin group. Vitamin pretreatment significantly lowered MDA, CD and OH. radical levels in heart tissues. In the liver tissues, adriamy cin effected a rise in all of the enzyme activities but MDA, CD, iron and OH. radical levels remained unchanged. The livers of the vitamin p lus group showed increases in CAT activity and iron levels. GSH-Px act ivity and MDA levels were decreased and, SOD, CD and OH. levels were u nchanged. By the electron microscopic examination; significant subcell ular changes were observed in the heart tissues of adriamycin group. T here were, however, no important subcellular changes in the heart tiss ues of the vitamin plus group, and in the liver tissues of adriamycin and vitamin groups. The results support the likelihood that the heart' s enzymatic antioxidant defense system was impaired and peroxidative r eactions were accelerated due to adriamycin treatment. Antioxidant vit amin pretreatment considerably lessens adriamycin-induced cardiotoxici ty, presumably mediated through elimination of OH. radical formed duri ng adriamycin metabolism in the heart tissue. The results of this stud y support the introduction of antioxidant vitamins in the amelioration of adriamycin-induced cardiotoxicity.