[Experimental study of the subacute toxicity of mitoxantrone and doxorubicin in rats (subcutaneous and/or intraperitoneal route)]

Abstract

The aims of this study were to compare experimentally the subacute cardiotoxicity of a new anthracycline, mitoxantrone (MIT) with doxorubicin (ADM), the reference anthracycline drug. Seventy nine male rats were divided into 5 groups receiving one of the drugs or a placebo by subcutaneous (SC) or intraperitoneal (IP) injection, each week for 13 weeks. The surviving rats were sacrificed at the 21st week. Group I comprised 16 rats which received 2 mg/kg AMD-IP. The mortality rate was 50% between the 14th and 18th week. Twelve of the 16 cases had a haemorrhagic ascites. The heart was normal macroscopically and on light microscopy. However, electro microscopy showed moderate myocytic degeneration. Group II comprised 16 rats which received 0.6 mg/kg MIT-IP. Morality was 100% at the 11th week. Groups III and IV comprised 32 rats; half of the animals were given 0.6 mg/kg MIT-SC and the other half 0.4 mg/kg MIT-SC. The results were identical: good clinical tolerance, normal macroscopy. Three cases of lymphocytic myocarditis and in 4 out of 8 cases very mild myocardial degeneration on electron microscopy. Group V comprised 15 rats which were given NaCl 9% SC or IP; there were no complications. These results show that mitoxantrone given IP produced major peritoneal toxicity. On the other hand, it was well tolerated when given SC and only produced mild myocardial degenerative changes.