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Oxidative Stress May Contribute to the Intestinal Dysfunction of Weanling Rats Fed a Low Protein Diet¹

Nicole Darmon^*,2, Marie-Agnès Pélissier, Martine Heyman^*, Robert Albrecht and Jehan-François Desjeux^*,,

^* Unité 290 de l'Institut National de la Santé et de la Recherche Médicale, Hôpital Saint-Lazare, 75010 Paris Laboratoire de Biologie du Conservatoire National des Arts et Métiers, 75141 Paris Cedex 03, France

Intestinal function is impaired in malnutrition. Because oxidative stress is a component of gastrointestinal injury, and mainutrition 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 ß-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 Isc induced by glucose and forskolin, as well as ß-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.

KEY WORDS: • rats • antioxidant enzymes • free radical damage • intestinal function • malnutrition

¹ Presented in part at the international meeting on Free Radicals and Aging organized by the Society for Free Radical Research, September 26–28, 1991, Institut Biomédical des Cordeliers, Paris, France [Darmon, N., Albrecht, R., Heyman, M. & Desjeux, J. F. Oxidative stress and intestinal function: effect of protein deficiency. Pélissier, M. A., Darmon, N., Smaïli, M., Attéba, S. & Albrecht, R. Lipid peroxidation related to antioxidant status in rat liver and small intestine: effect of protein deficiency and food restriction.].

² To whom correspondence and reprint requests should be addressed.

Manuscript received 9 July 1992. Revision accepted 8 January 1993.

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