Gossypol-hypokalaemia interrelationships.

Around 1% of 8806 volunteers taking gossypol as a male contraceptive had hypokalaemic paralysis and more had simple hypokalaemia, the direct cause being renal potassium loss. In gossypol takers not showing hypokalaemia, serum potassium levels were within the normal range but were significantly lower than levels in controls. In the majority of patients suffering from gossypol-induced hypokalaemia, recovery was prompt and complete following potassium repletion, but in some men there were recurrent attacks of hypokalaemia during a period of several months to years after cessation of gossypol treatment. The incidence of hypokalaemic paralysis in gossypol takers showed distinct regional differences, being much higher in Nanjing, where the dietary potassium level of the inhabitants was low, than in Taian, where the dietary potassium level was high. In rats fed a low-K fodder, gossypol reduced the intracellular Mg and K concentrations of the skeletal muscle, while in regularly fed rats, this effect of gossypol was not observed. A potassium deficient diet could thus be considered a contributing factor in the development of gossypol-induced hypokalaemia. Potassium deficiency has also been shown to enhance the anti-spermatogenic effect of gossypol. Suggested mechanisms for the development of gossypol-induced hypokalaemia include inhibition of Na-K-ATPase activity, stimulation of prostaglandin biosynthesis, damage to the renal tubule, and modification of membrane transport.