Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide

Abstract

The neonatal small intestine is susceptible to damage by endotoxin, but effective methods for prevention and treatment are lacking. N-acetylcysteine (NAC) is a widely used precursor of L: -cysteine for animal cells and plays an important role in protecting cells against oxidative stress. This study was conducted with the lipopolysaccharide (LPS)-challenged piglet model to determine the effects of NAC on intestinal function. Eighteen piglets were randomly allocated into control, LPS and LPS+NAC groups. The control and LPS groups were fed a corn- and soybean meal-based diet, and the LPS+NAC group was fed the basal diet +500mg/kg NAC. On days 10, 13 and 20 of the trial, the LPS and LPS+NAC groups received intraperitoneal administration of LPS (100μg/kg BW), whereas the control piglets received saline. On day 20 of the trial, D-: xylose (0.1g/kg BW) was orally administrated to all piglets 2h after LPS or saline injection, and blood samples were collected 1h thereafter. One hour blood xylose test was used to measure intestinal absorption capacity and mucosal integrity, and diamine oxidase (DAO) was used as a marker of intestinal injury. On day 21 of the trial, pigs were killed to obtain the intestinal mucosa. Compared to the control, LPS challenge reduced (P<0.05) the concentrations of D-: xylose (a marker of intestinal absorption) in plasma, activities of DAO in the jejunal mucosa, the ratio of villus height to crypt depth in the jejunal mucosa, RNA/DNA and protein/DNA in the jejunal and ileal mucosae, while increasing (P<0.05) DAO activity in plasma and caspase-3 expression in the intestinal mucosa. The adverse effects of LPS were partially ameliorated (P<0.05) by NAC supplementation. Moreover, NAC prevented the LPS-induced decrease in claudin-1 and occludin expression in the jejunal and ileal mucosae. Collectively, these results indicate that dietary NAC supplementation alleviates the mucosal damage and improves the absorptive function of the small intestine in LPS-challenged piglets.