Chronic low intake of protein or vitamins increases the intestinal epithelial cell apoptosis in Wistar/NIN rats

OBJECTIVE: Malnutrition decreases antioxidant defense and increases oxidative stress in the intestine. We studied the effects of long-term restriction of food, protein, and vitamins on intestinal epithelial cell (IEC) apoptosis and the underlying mechanisms. METHODS: Weanling, Wistar/NIN male rats were fed ad libitum with a control diet, 75% protein-restricted diet, or 50% vitamin-restricted diet for 20 wk. The food-restricted group received 50% of the diet consumed by control rats. IEC apoptosis was monitored by morphometry, Annexin V binding, M30 CytoDeath assay, and DNA fragmentation. Structural and functional integrity of the villus were assessed by the ratio of villus height to crypt depth, and alkaline phosphatase and lys, ala-dipeptidyl aminopeptidase activities, respectively. Oxidative stress parameters, caspase-3 activity, and expression of Bcl-2 and Bax were determined to assess the probable mechanisms of altered apoptosis. RESULTS: Protein and vitamin restrictions but not food restriction significantly increased IEC apoptosis and only vitamin restriction altered structural and functional integrity of villi. Increased levels of protein carbonyls, thiobarbituric acid reactive substances, and caspase-3 activity along with decreased glutathione levels and Bcl-2 expression were observed in IECs of these rats, whereas food restriction did not affect these parameters. CONCLUSIONS: Protein restriction increased only IEC apoptosis, whereas vitamin restriction also affected the structure and function of villi. Modulation of the pathway mediated by mitochondria through increased oxidative stress appears to be the probable mechanism underlying this effect.