Chronic toxicity of gossypol and the relationship to its metabolic fate in dogs and monkeys

Great differences between the toxicities of gossypol in dogs and monkeys were seen. Daily doses of 2-5 mg/kg were given orally to 6 dogs. ECG manifested abnormalities 4 weeks after the beginning of the treatment, but the blood routine, hepatic function and renal function tests remained normal. Four dogs died of cardiac toxicity on days 42, 63, 77 and 86, repectively. Severe myocardial damages were noted histologically. In the dogs survived, their toxic cardiac signs and histological changes disappeared 1 year after withdrawal of gossypol. In monkeys all biochemical parameters, ECG and activities remained normal during oral medication period of 2 years at a daily dose of 4 mg/kg. Histological studies on liver, kidneys, hearts and adrenal glands revealed n difference bwtween 3 treated monkeys and 2 control monkeys. There were marked species differences of alimentary absorption and excretion of gossypol between dogs and monkeys. Gossypol was absorbed less and excreted more in monkeys than in dogs. Perhaps this is one of the reasons responsible for the higher toxicity of gossypol in dogs than in monkeys. The role played by the dietary constituents is still a matter of consideration.