Marked changes in endogenous antioxidant expression precede vitamin A-, C-, and E-protectable, radiation-induced reductions in small intestinal nutrient transport

Abstract

Rapidly proliferating epithelial crypt cells of the small intestine are susceptible to radiationinduced oxidative stress, yet there is a dearth of data linking this stress to expression of antioxidant enzymes and to alterations of intestinal nutrient absorption. We previously showed that 5 -14 d after acute γ-irradiation, intestinal sugar absorption decreased without change in antioxidant enzyme expression. In the present study, we measured antioxidant mRNA and protein expression in mouse intestines taken at early times postirradiation. Observed changes in antioxidant expression are characterized by a rapid decrease within 1 h postirradiation, followed by dramatic upregulation within 4 h, and then downregulation a few days later. The cell type and location expressing the greatest changes in levels of the oxidative stress marker 4HNE and in antioxidant enzymes are, respectively, epithelial cells responsible for nutrient absorption and the crypt region comprised mainly of undifferentiated cells. Consumption of a cocktail of antioxidant vitamins A, C and E, before irradiation, prevents reductions in transport of intestinal sugars, amino acids, bile acids and peptides. Ingestion of antioxidants may blunt radiation-induced decreases in nutrient transport, perhaps by reducing acute oxidative stress in crypt cells, thereby allowing the small intestine to retain its absorptive function when those cells migrate to the villus days after the insult.

Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice

“…Intestinal uptake rates were determined as described previously (45,46). Briefly, 1-cm segments of the proximal small intestine were individually mounted and everted on grooved steel rods.…”

High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation

“…The nonmetabolizable glucose analog, 3-O-methylglucose, is absorbed by the same transporter mediating D-glucose uptake, and their comparative uptake rates are often used to distinguish effects on membrane transport from those on glucose metabolism in the cytosol (3). Our studies have shown that transport rates of these nutrients are affected differently when mice are exposed to acute doses of low-LET 137 Cs gamma rays (4, 5). However, the effect of chronic irradiation on nutrient transport is not known and agents to prevent or mitigate such reductions have not been assessed.…”

“…A combination of vitamins A, C and E reduced bone marrow toxicity caused by radioimmunotherapy with 131 I-labeled antibodies (10). Furthermore, we have demonstrated a diet enriched in vitamins A, C and E (vitamin ACE) protects intestinal transport of these nutrients under acute irradiation conditions (4). …”

Health Risks of Space Exploration: Targeted and Nontargeted Oxidative Injury by High-Charge and High-Energy Particles

“…This dose can be as high as 30-40% of the total dose deposited by an HZE particle (62,101,209). However, a particles emitted from common radioactive sources (e.g., 238 Pu or 241 Am) used for cellular experiments do not pose such problems. Interpretations of the apparent nontargeted effects are relatively straightforward as these a particles do not produce secondary radiations that crossirradiate neighboring cells (126).…”

“…Earlier studies indicated that nutrient absorption in mice was significantly reduced following the exposure to c rays (217,239). Decreases in intestinal sugar absorption were associated with a rapid decrease in SOD and catalase abundance, followed by dramatic upregulation within 4 h and then downregulation a few days later (238).…”