Effects of gossypol on the kidney with special emphasis on potassium (K) excretion

The overall and renal toxicity of racemic gossypol acetic acid was assessed in 6 mongrel dogs. Oral racemic gossypol acetic acid was given orally at doses increasing from 10 to 40 mg/d for a total of 6 weeks in 3 female dogs and from 40 to 80 mg/d for a total of 4 weeks in 3 male dogs. The animals were then sacrificed. Drug tolerance was excellent. Pathological examination of the liver and heart was normal. Renal function remained normal. The renal excretion of K, Mg, phosphate and acid remained normal. Serum K remained within the range appropriate for animals on a K-free diet. Pathological examination of the kidney disclosed mild proximal tubule vacuolization similar to that observed in animals on a K-free diet and small brownish pigment deposits in a few tubular cells. Spermatogenesis was arrested in the testes of one of the 3 male dogs. We conclude that short exposure to 10 to 80 mg/day of gossypol does not result in detectable toxic effect. Neither significant hypokalemia nor a tubular K leak were observed.