Abstract
The effect of gossypol acetic acid (gossypol) on plasma lipid concentrations was studied in adult male cynomolgus monkeys consuming a diet containing 0.19 mg cholesterol/Kcal. Gossypol was administered orally at 5 (n = 4) or 10 (n = 3) mg/kg/day for 6 months. A significant decrease in total plasma cholesterol (TPC) and low density lipoprotein and very low density lipoprotein-cholesterol (LDL + VLDL-chol) concentrations was observed without any significant decrease in plasma high density lipoprotein-cholesterol (HDL-chol) levels among 10 mg/kg/day gossypol-treated animals. This is a new therapeutic property of gossypol that has been previously reported. No appreciable differences were observed in plasma levels of TPC and LDL + VLDL-chol among 5 mg/kg/day gossypol-treated animals when compared to controls until the gossypol dosage was increased to 10 mg/kg/day, thus suggesting that hypolipidemic effect of gossypol is dose-dependent. In general, no adverse clinicopathological findings were noted except a temporary diarrhea and loss of appetite among 10 mg/kg/day gossypol-treated animals during the initial stages of treatment. In conclusion, it is tempting to speculate that gossypol might possibly reduce the intestinal absorption of dietary cholesterol or it may reduce the hepatic synthesis of low density lipoproteins. These results also suggest that gossypol may be a particularly useful drug in lowering plasma cholesterol concentrations in addition to its previously demonstrated antifertility properties in males.
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