Reduction of chronic daunorubicin cardiotoxicity by ICRF-187 in rabbits

Abstract

To determine whether ICRF-187 (NSC-169780) would alter chronic daunorubicin (NSC-82151) cardiac toxicity, male New Zealand rabbits were given 3.2 mg/kg or daunorubicin iv alone or 30 minutes after 12.5 or 25.0 mg/kg of ICRF-187 ip at 3-week intervals. Control rabbits received either saline iv or ICRF-187 (12.5 or 25.0 mg/kg) ip on the same schedule. Three weeks after the fifth injection, the animals were sacrificed. The frequency and extent of cellular alterations were graded on a scale of 0 to 4. Lesions consisting mainly of vacuolization and myofibrillar loss were noted in the hearts of all 12 rabbits given daunorubicin alone. The severity ranged from 1 to 3 (average 1.8). In contrast, no abnormalities were noted in one of five (12.5 mg/kg) and three of seven (25.0 mg/kg) ICRF-treated rabbits. The remaining eight hearts from both pretreatment groups displayed animal alterations ranging from 0.5 to 1.0 (average 0.9). Thus, concurrent administration of the antineoplastic agent ICRF-187 may offer a means of reducing chronic daunorubicin cardiac toxicity.