The effects of gossypol on the antioxidant defense system of the rat liver

Rats were dosed with gossypol acetic acid by subcutaneous injection or gavage to determine its effect on some of the key antioxidant defense systems of the liver. Gossypol, a pigment of cottonseeds, is a known hepatoxin and antifertility agent, but its mechanism of action is presently unknown. The hepatic antioxidants catalase, ascorbate, α-tocopherol, glutathione peroxidase glutathion, glutathione reductase, copper-zinc superoxide dismutase, manganese superoxide dismutase and glucose-t-phosphate dehydrogenase were assayed in this study. Of these 9 antioxidants, catalase, ascorbate, glutathione peroxidase and copper-zinc superoxide dismutase were significantly reduced in the livers of both injected and gavaged rats compared to the respective controls. Deficiency of these key antioxidants would make hepatocytes highly vulnerable to oxidative injury. Thus, oxidative injury may be central to the pathogenesis of gossypol induced hepatic necrosis.