Oxidative Stress May Contribute to the Intestinal Dysfunction of Weanling Rats Fed a Low Protein Diet

Abstract

Intestinal function is impaired in malnutrition. Because oxidative stress is a component of gastrointestinal injury, and malnutrition may reduce antioxidant defenses, we investigated the involvement of oxidative stress in the intestinal dysfunction due to malnutrition. Weanling rats were fed either a normal protein (22% casein) or a low protein (6% casein) diet for 4 wk. In intestinal homogenates, we assessed free radical damage and enzymatic antioxidant defenses. In jejunal fragments mounted in Ussing chambers, we measured ionic transport by short-circuit current (Isc) and protein permeability by transepithelial fluxes of beta-lactoglobulin. Catalase activity and the thiobarbituric acid-reacting substances concentration were greater in intestinal mucosa of the low protein group, whereas the glutathione concentration and the activities of superoxide dismutase and Se-dependent glutathione peroxidase were the same as in the normal protein group intestinal mucosa. Both basal Isc and the delta Isc induced by glucose and forskolin, as well as beta-lactoglobulin fluxes, were higher in the low protein group. Exogenous H2O2 stress increased Isc significantly more in the low protein than the normal protein group but did not alter protein permeability. These results show that malnutrition induces both intestinal free radical damage and altered epithelial transport, suggesting that oxidative stress may contribute to the intestinal dysfunction associated with malnutrition.