Some aspects of the toxicity of gossypol were investigated in ethanol-
fed, gossypol-treated Sprague-Dawley rats, with and without protein ma
lnutrition. Serum creatine phosphokinase activity was depressed in all
gossypol-treated rats and gossypol caused greater decreases than etha
nol in those animals that were fed the normal diet. Even though the ad
renal glands were enlarged in all gossypol-treated rats, this was acco
mpanied by depressed serum cortisol levels. Histopathological findings
, including vacuolar degeneration of hepatocytes and dilation of the s
inusoids in the liver, atrophy and leucocytic infiltration of cardiac
myofibres, vacuolation of the renal glomerulus and cellular depletion
of the spleen and thymus, were most severe in the protein-malnourished
, gossypol-treated rats; these were generally absent in the other grou
ps. These findings indicated that either adequate levels of protein in
the diet and/or ethanol consumption have the effect of reducing gossy
pol toxicity, probably by reducing the amount of gossypol available fo
r tissue exposure through enhanced metabolism and/or clearance from th
e body. However, an evaluation of the metabolic pathways involved in g
ossypol metabolism in ethanol-fed individuals might provide a better u
nderstanding of these observations.