[Effect of doxorubicin on animals in multiple intravenous administration]

Toxicity of doxorubicin prepared with an original chemical method from rubomycin (daunomycin) was studied on albino rats and dogs. The antibiotic was administered intravenously in multiple doses. A significant loss of the body weight, a decrease in the relative weight of the spleen, thymus and ovary and an increase in the relative weight of the heart, kidneys and adrenal gland were observed in the rats after daily administration of doxorubicin in various doses 5 times. In a dose of 0.5 mg/kg doxorubicin was lethal for the dogs after 5, 7 and 10 administrations. Multiple administration of the antibiotic in doses of 0.25 and 0.125 mg/kg did not result in death of the dogs. There were areas of alopecia on the belly and joints, ulcers, body weight loss, increased urea levels in serum and diarrhea before death. The faeces contained significant admixtures of blood. Doxorubicin had an inhibitory effect on hemopoiesis of the albino rats and dogs. Before death bone marrow aplasia was recorded. After discontinuation of doxorubicin administration the inhibitory effect of the antibiotic on hemopoiesis persisted for 2-3 days. Histological examination of the organs and tissues of the animals killed at different periods after multiple intravenous administration of doxorubicin in various doses showed that doxorubicin had mainly the damaging effect on the gastrointestinal epithelium, heart muscle, epithelium of the proximal tubuli of the kidneys, lymphoid organs and testis. The damage depended on the dose of doxorubicin and duration of its use. By the character of the toxic effect and the size of the doses inducing certain effects doxorubicin made in the USSR did not differ from the analogous foreign drug.