EFFECT OF VITAMIN-A ADMINISTRATION ON RESISTANCE OF RAT-HEART AGAINSTDOXORUBICIN-INDUCED CARDIOTOXICITY AND LETHALITY

The peroxyl radical-scavenging activity of vitamin A has been exploite d to obtain protection against peroxidative damages induced in rat hea rt by administration of an acute dose of doxorubicin (10 mg/kg, in vei n). Peroxidative lesions were evaluated by both biochemical and histol ogical assays, 48 hr after the injection of doxorubicin. Heart tissue from rats receiving doxorubicin showed a marked increase of protein ca rbonyl levels, and of membrane conjugated dienes, as well as a decreas e of membrane protein thiols. Abnormal chemistries, including a large increase of the activity of serum lactate dehydrogenase and creatine p hosphokinase, an index of the myocardial damage caused by doxorubicin, were also observed. Pretreatment of rats with 25 I.U./kg b.wt. of vit amin A, once a day for 2 days, before injecting doxorubicin, substanti ally reduced the peroxidative damage to heart lipids and proteins, and markedly lowered the serum values of lactate dehydrogenase and creati ne phosphokinase to values close to those of control rats. The signifi cant prevention of doxorubicin-induced cardiomyopathy by vitamin A was evident from the histopathological pattern observed after light micro scopy. The dosage of vitamin A useful to obtain the protective effect appears safe and does not injure the liver, as indicated by light micr oscopy of the tissue. A survival study, carried out by injecting rats with a single injection of 10 mg/kg of doxorubicin, showed that pretre atment with 25 I.U. of vitamin A per kg significantly increased surviv al rate of the animals. In comparison with rats receiving doxorubicin alone, 100% of which had died of heart failure within 3 weeks, 85% of vitamin A-pretreated animals survived for up to the end of a 6-weeks o bservation, and appeared healthy and active. Light microscopy showed a well preserved myocardial tissue. These results may suggest to explor e the use of low doses of vitamin A to reduce doxorubicin-induced card iotoxicity in cancer chemotherapy.