Chronic diarrhea impairs intestinal antioxidant defense system in rats at weaning

The aim of the present study was to evaluate the influence of severe protei n-energy malnutrition on the antioxidant defense system in the small and la rge intestine in rats at weaning. Chronic diarrhea and the subsequent malnu trition were induced by oral intake of a lactose-enriched diet. Twenty rats were weaned at 21 days of age, and the control group was fed a semipurifie d synthetic diet for two weeks. The malnourished group was fed the same die t but carbohydrates were replaced by lactose, and they developed diarrhea o ne day after. Rats were killed, and macroscopic and histological features w ere analyzed, DNA content was measured, and alkaline phosphatase, myelopero xidase, and gamma -glutamyltranspeptidase activities were determined to ass ess the degree of intestinal injury. Glutathione levels as well as the acti vities of intestinal glutathione transferase, glutathione reductase, total glutathione peroxidase, selenium-dependent glutathione peroxidase, superoxi de dismutase, and catalase were measured to study the antioxidant defense s ystem. Malnourished rats showed loss of body weight and an increase in leng th and weight in jejunum and ileum, while no significant changes were obser ved in colon. Epithelial cells showed fewer and shorter microvilli, larger mitochondria with low inner density and loss of cristae, dilated endoplasmi c reticulum, and Golgi apparatus. The protein-to-DNA ratio was higher in th e jejunum, ileum, and colon of malnourished rats. Glutathione levels decrea sed 40% in jejunum and 50% in colon of malnourished rats. A 40-50% decrease in the activity of all the enzymes of the antioxidant defense system was o bserved in the jejunum and ileum of malnourished rats, while only catalase and glutathione transferase activities decreased 50% in colon. These result s suggest that early chronic diarrhea and severe protein-energy malnutritio n impair the antioxidant defense system in both the small and large intesti ne, which may have a role in the pathogenesis and maintenance of the viciou s circle of malabsorption-diarrhea-malnutrition in infancy.