The actions of gossypol on the physiologic antioxidant defense system
Bender, Holly S.
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Gossypol , a yellow polyphenolic pigment found in cottonseeds, is known to promote the production of reactive species of oxygen in vitro, and has toxic actions on spermatogenic epithelium, hepatocytes and cardiac myocytes in vivo. Species vary in tissue sensitivity to the toxic effects of gossypol. The spermatogenic epithelium is the most sensitive tissue to gossypol in rats, followed by the liver. Toxic effects to the rat heart are found only after prolonged administration of gossypol. The antioxidant defense system that protects cells from injury by reactive species of oxygen was examined in the present study to determine a possible pathogenesis for gossypol associated tissue damage. The concentrations of several hepatic antioxidants including catalase, glutathione peroxidase, ascorbate and copper-zinc superoxide dismutase were decreased in gossypol treated rats. Catalase, glutathione peroxidase, ascorbate and glucose-6-phosphate dehydrogenase were decreased in the testis. In contrast, antioxidants including catalase and glutathione reductase were increased in the hearts of gossypol treated rats. The selective inhibition of testis and hepatic antioxidants may account for the greater sensitivity of these organs to reactive oxygen species generated by gossypol. The rat heart may adapt to oxidative insult by inducing the production of antioxidants. Glucose-6-phosphate dehydrogenase activity was decreased in the testis but not liver or heart of gossypol treated rats. This important enzyme is known to produce NADPH reducing equivalents for testosterone biosynthesis and the glutathione antioxidant system. In the present study, micromolar concentrations of gossypol inhibited glucose-6-phosphate dehydrogenase in a competitive manner with respect to glucose-6-phosphate. This may explain the degeneration of spermatogenic epithelium as well as decreases in serum testosterone concentrations in gossypol treated rats. Gossypol is known to cause infertility in women and female rats. The present study found irregularities in the estrous cycles and ultrastructural changes in endometrial macula adherentes of gossypol treated female rats.
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