Modulatory influence of tin-protoporphyrin on gossypol-induced alterations of heme oxygenase activity in male Wistar rats.

Gossypol--a male contraceptive is toxic and causes anorexia, reduction in body weight, hypokalemia etc. It prevents liberation of oxygen from oxyhemoglobin and has hemolytic effect on erythrocytes and leads to microcytic hypochromic anemia. SnPP has been shown to either competitively suppress or to significantly ameliorate a variety of naturally occuring or experimentally induced forms of jaundice in animals and man by inhibiting heme degradation. In this paper novel tissue-dependent response to differential dosing regimen of gossypol and gossypol in association with Sn-protoporphyrin (SnPP) is described. Gossypol was found to be a stimulator of heme oxygenase activity in the liver and kidney to varying degrees. This tissue response contrasted with that of the spleen, where gossypol decreased the activity of the enzyme. The increase in enzymatic activity was accompanied by a decline in the total microsomal protein content on gossypol administration. The gossypol mediated an increase of heme oxygenase activity, elevated bilirubin levels leading to hyperbilirubinemia. The stimulatory effect of gossypol was counteracted to a considerable extent when SnPP was simultaneously administered. Hence, we envision the importance of combined rather than single exposures in defining the realms of toxicology of these and other related drugs. We further envisage the existence of important gossypol-heme interactions in the regulation of heme metabolism.