Anthracycline cardiotoxicity in a black rhinoceros (Diceros bicornis): Evidence for impaired antioxidant capacity compounded by iron overload

Two weeks before dying of congestive heart failure, a juvenile black rhinoc eros (Diceros bicornis minor) received a single low dose of doxorubicin as part of combination chemotherapy for acute lymphoblastic leukemia. Diffuse hemosiderosis was present at necropsy in a pattern indicative of dietary ir on overload, but unique iron-positive degenerative lesions were found in is olated myocardiocytes. Serum analyses revealed hyperferremia, 87% transferr in saturation, and 5- to 10-fold elevations in ferritin concentration, refl ecting markedly increased tissue iron stores. Since both toxic and therapeu tic effects of anthracyclines are mediated by formation of reactive free ra dicals via iron-catalyzed reactions, these observations suggest that iron o verload may have enhanced myocardial susceptibility to cardiotoxic effects of doxorubicin. Impairments in other myocardial antioxidant defenses, such as deficiencies in catalase and glutathione S-transferase that are known to exist in rhinoceros erythrocytes, may have been underlying factors contrib uting to an inherent sensitivity of rhinoceros tissues to oxidant-induced i njury.