Reduction by ICRF-187 of Acute Daunorubicin Toxicity in Syrian Golden Hamsters

Administration of a single dose of daunorubicin (25 mg/kg) to Syrian golden hamsters caused a marked decrease in food consumption and body weight and death within 1 to 3 weeks. The severity of acute daunorubicin toxicity was reduced by pretreatment with ICRF-187 at doses of 12.5 mg/kg or greater. Although most animals pretreated with 12.5 to 50 mg ICRF-187/kg were alive after 5 weeks, body weight was below control levels. Animals pretreated with 100 mg ICRF-187/kg were the only group able to regain initial weight loss and increase body weight above the preinjection control level. Different degrees of protection were observed when the 100 mg/kg dose of ICRF-187 was given at various times before and after daunorubicin. Significant numbers of animals (45%) survived when ICRF-187 was given 48 h before daunorubicin. Optimal survival was observed when 100 mg ICRF-187/kg was given from 3 h before to 3 h after daunorubicin. The protective effect of ICRF-187 was lost when it was administered more than 6 h after daunorubicin. The lethal effects of high doses of daunorubicin may be due to profound gastrointestinal toxicity. Alterations in the heart, liver, or kidneys did not appear to be of sufficient magnitude to be responsible for the lethality in the hamsters. In contrast, marked histopathological changes were found throughout the entire length of the gastrointestinal tract from the colon to the tongue. ICRF-187 appears capable of altering daunorubicin toxicity on this tissue.