Inhibition of cardiotoxic, nephrotoxic and neurotoxic effects of doxorubicin by ICRF-159.

Cardiotoxicity of doxorubicin, 2 mg/kg i.p. twice weekly in rats, was assessed by serial electrocardiography and electron microscopy. The toxic effects were markedly inhibited by ICRF-159, 50 mg/kg p.o. given 1 h before doxorubicin. The development of nephropathy characterized by proteinuria, hyperlipidemia and glomerular and tubular changes was significantly retarded, and the degenerative changes of peripheral nerves were markedly reduced. On the other hand, ICRF-159 enhanced the depressant effects of doxorubicin on bone marrow function. Doxorubicin reduced body weight gain, caused ascites, decrease in heart and thymus weight, and increase in liver and kidney weight. These changes were also inhibited or attenuated by ICRF-159 pretreatment.