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 rhinoceros (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 iron overload, but unique iron-positive degenerative lesions were found in isolated myocardiocytes. Serum analyses revealed hyperferremia, 87% transferrin saturation, and 5- to 10-fold elevations in ferritin concentration, reflecting markedly increased tissue iron stores. Since both toxic and therapeutic effects of anthracyclines are mediated by formation of reactive free radicals via iron-catalyzed reactions, these observations suggest that iron overload 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 contributing to an inherent sensitivity of rhinoceros tissues to oxidant-induced injury.
Paglia
D E
DE
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, CA 90095-1732, USA. dpaglia@pathology.medsch.ucla.edu
Radcliffe
R W
RW
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002570:Ceruloplasmin / Q000032:analysis; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D017809:Fatal Outcome; D005260:Female; D005293:Ferritins / Q000032:analysis; D006242:Haptoglobins / Q000032:analysis; D006333:Heart Failure / Q000139:chemically induced / Q000662:veterinary*; D006485:Hemosiderin / Q000032:analysis; D006486:Hemosiderosis / Q000473:pathology / Q000662:veterinary*; D007501:Iron / Q000097:blood; D009206:Myocardium / Q000473:pathology; D010527:Perissodactyla; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000662:veterinary*; D014168:Transferrin / Q000032:analysis
D000903:Antibiotics, Antineoplastic; D006242:Haptoglobins; D014168:Transferrin; D004317:Doxorubicin; D005293:Ferritins; D006485:Hemosiderin; D007501:Iron; D002570:Ceruloplasmin