Dietary cottonseed protein can reduce the severity of retinoid-induced hypertriglyceridemia

Hypertriglyceridemia is frequently noted as a side effect when retinoids (e.g., 13-cis-retinoic acid) are used in human chemoprevention trials. Dietary oilseed proteins (e.g., cottonseed and soy protein) are known to reduce the severity of diet-induced hypertriglyceridemia, but their influence on drug-induced hypertriglyceridemia has not been studied previously. In the present study, the ability of dietary cottonseed protein (as cottonseed flour) to prevent drug-induced hypertriglyceridemia was investigated by feeding male Fischer 344 rats diets having casein or cottonseed protein flour with or without 13-cis-retinoic acid. Animals were fed diets for 2 weeks. Retinoid administration was associated with the induction of hypertriglyceridemia and with changes in serum fatty acid profile, the most noticeable being lowered levels of arachidonic acid. Levels of this fatty acid were 35 and 54% of control levels for retinoid-treated animals fed casein and cottonseed flour, respectively. Animals fed cottonseed flour had lower serum triglyceride levels than ones fed casein for both retinoid-containing and control diets. Dietary cottonseed flour had no effect on food intake or body weight and did not affect serum drug levels. Thus, dietary cottonseed protein can reduce the severity of retinoid-induced hypertriglyceridemia without having adverse effects on food intake or growth; in addition, because levels of 13-cis-retinoic are unaffected by cottonseed protein, it is unlikely that the chemopreventive effectiveness of the drug will be compromised by the inclusion of this protein in the diet.