N-carbamylglutamate and L-arginine Supplementation Improve the Intestinal Oxidative Resistance of the Intrauterine Growth-retarded Ovine Fetuses 

Abstract

Abstract Background: The maternal under nutrition-induced intrauterine growth retardation (IUGR) is associated with intestinal oxidative injury in fetuses and neonates in various animal models. However, whether maternal dietary Arginine (Arg) and N -carbamylglutamate (NCG) supplementation during IUGR alters fetal small intestine redox status is unclear. Objective: The ovine model of IUGR was used to elucidate whether dietary supplementation of rumen-protected Arg (RP-Arg) and NCG modulates the fetal intestinal oxidative resistance via the nitric oxide (NO) -dependent pathway. Methods: On day 35 of gestation, 32 twin-bearing Hu ewes were randomly assigned into 4 treatment groups, 8 ewes each. The first and second groups received 100% (Control, CON) and 50% (restricted, RES) of NRC-recommended pregnancy nutrient requirements, respectively. The third and fourth treatment groups included the RES ewes supplemented with 20 g/day of RP-Arg (RES+ARG) or 5 g/day of NCG (RES+NCG), respectively. On day 110 of gestation, fetal blood and intestinal specimens were collected and assayed for oxidative damage biomarkers. Results: The NCG or Arg-supplemented RES ewes elevated the fetal jejunal NO concentrations and NO synthase (NOS) activity, but decreased the fetal jejunal and plasma concentrations of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) ( P < 0.05) compared with those in the RES ewes. Further, the NCG or Arg treatment increased the contents of catalase (CAT), glutathione peroxidase 1 (GPx1), nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), heme oxygenase (HO-1), quinone oxidoreductase 1 (NQO1), claudin-1, zonula occludens-1 (ZO-1), epithelial NOS (eNOS) and inducible NOS (iNOS) in the fetal jejunum ( P < 0.05). Conclusion: These results indicate that both NCG and Arg supplementation for RES ewes help maintain intestinal function in fetuses experiencing IUGR through modulating the oxidation status.