Effect of Phenobarbital on the Level of Gossypol in the Liver and the Effect of Gossypol and Phenobarbital on Liver Microsomal O-Demethylation and Lipid Peroxidation Activities in the Rat
The metabolism of xenobiotics in the liver by enzymes associated with the endoplasmic reticulum is markedly enhanced by phenobarbital treatment. In the reported experiments, intraperitoneal injection of sodium phenobarbital reduced the concentration of gossypol, a xenobiotic, in the livers of rats fed 0.05 and 0.075% free gossypol. The effect of gossypol on liver microsomal p-nitroanisole demethylase and lipid peroxidation was studied in both sodium phenobarbital-treated and nontreated rats. Liver lipid peroxidation activity was found to be inversely related to the gossypol concentration in the liver. In a liver postmitochondrial supernate prepared from rats that were gavaged with 25, 50, and 100 mg gossypol/kg of body weight, lipid peroxidation activity was inhibited while O-demethylation of p-nitroanisole was not affected. Intraperitoneal injection of sodium phenobarbital increased p-nitroanisole demethylase activity but did not overcome the gossypol-inhibited lipid peroxidation. There was no effect on O-demethylation in rats fed 0.075% free gossypol; however, lipid peroxidation was drastically reduced. The gossypol-inhibited NADPH and ascorbate-induced lipid peroxidation in microsomes isolated from the livers of rats gavaged with gossypol were overcome by adding Fe3+ to the incubation medium.