米托蒽醌的急性毒性研究

A study of acute toxicity of mitoxantrone

Acute toxicity of mitoxantrone (DHAQ) synthetized by Department of Organic Chemistry, School of Pharmacy, WCUMS was studied in mice and dogs. The toxic effects were compared with those of adriamycin (ADR). The LD50 were 6.6 +/- 1.3 and 7.1 +/- 1.6 mg/kg DHAQ, 7.9 +/- 2.1 and 10.7 +/- 2.2 mg/kg ADR (P = 0.95) respectively on observation with a single dose i.v. and i.p., for 21 days in Kunming mice. The toxicity appeared to be delayed with DHAQ and ADR. The earliest death occurred on 4th day after treatment in mice. In the third week still a few died. There were obvious decreases in WBC counts in the peripheral blood of mice receiving either 1-2.5 mg/kg DHAQ or 2.5-5 mg/kg ADR with a single dose i.p.. The WBC count could return to normality after 3 weeks with the withdrawal of the drugs. On electron microscopic examination of myocardial samples from mice 4 days after a single dose of 20 mg/kg DHAQ i.p., mitochondria swelling and vacuoles formation in some cells were shown. Besides the above-mentioned changes, some myocytes exhibited disorientation and loss of myofilaments in the mice which received equivalent dose of ADR. In dogs anaesthetized a temporary falling of blood pressure and slowing of heart rate were observed following 5-10 mg/kg DHAQ i.p.. When a dose of 50-100 mg/kg was given, the blood pressure dropped continuously until death.