Cardiotoxic and Possible Leukemogenic Effects of Adriamycin in Nonhuman Primates

Abstract

10 monkeys (macaques) received adriamycin by monthly intravenous injections at 12 mg/m² (1 mg/kg). 8 of the 10 monkeys developed congestive heart failure at an average cumulative adriamycin dose (310 mg/m²) well below that considered the safe upper limit (550 mg/ m²) in man. Histologically, the myocardial lesions resembled those found in human anthracycline-induced cardiomyopathy. 1 of the 10 monkeys developed acute myeloblastic leukemia after receiving 324 mg/m² of adriamycin; the 10th monkey is alive and well 26 months after the last dose of drug. Our results suggest that adriamycin is a more potent cardiotoxin in monkeys than in man, and that leukemia may be a consequence of prolonged treatment with this drug.

Dilative cardiomyopathy leading to congestive heart failure in a male squirrel monkey (Saimiri sciureus)

“…Taurine deficiency has been well documented as a nutritional deficiency leading to dilative cardiomyopathy in cats [12]. Cardiotoxic agents such as adriamycin can also result in dilative cardiomyopathy [14,17,20]. Dilative cardiomyopathy has been observed in wild caught owl monkeys (Aotus sp.)…”

The minipig as a new model for the evaluation of doxorubicin‐induced chronic toxicity

“…The toxic effects of doxorubicin have been investigated comprehensively in various animal models, e.g. dogs (Astra et al ., ), rabbits (Solcia et al ., ), monkeys (Sieber et al ., ) and rats (Thompson et al ., ). Mouse models have also been used extensively (Shuai et al ., ; Desai et al ., ), however, while providing important insights into doxorubicin‐induced toxicity and possible interventions, there are several limitations that question the clinical relevance of the mouse model to humans (Desai et al ., ).…”

Possible cardiotoxicity associated with low‐dose doxorubicin during chemotherapy in a ring‐tailed lemur (Lemur catta) with multicentric lymphoma

“…13 Cardiotoxicity is the most common cumulative adverse effect of DOX treatment, well documented in humans and veterinary species, with only a published report in nonhuman primates. [13][14][15][16][17] Histopathology of human DOX cardiomyopathy, though not exclusive of other causes of myocardial degeneration, is unique and reliably identified in cases of DOX cardiotoxicity. 16 The cardiac lesions observed at postmortem examination in this lemur are consistent with prior descriptions of DOX-induced cardiotoxicity in humans and other species.…”

“…DOX cardiotoxicity is a complex and only partially understood condition in humans and animals. 7,[13][14][15][16][17][18][22][23][24] Increased risk of DOX toxicity has been linked with iron overload in animals and humans, [24][25][26] and captive lemurs are a species of concern for dietary iron overload. 27 Iron increases the risk of DOX cardiotoxicity by forming anthracycline-iron complexes that potentiate reactive oxygen species causing significant oxidative damage, particularly targeting mitochondriarich cardiomyocytes.…”