title: N-Acetylcysteine improves intestinal function in lipopolysaccharides-challenged piglets through multiple signaling pathways.
abstract: This study determined whether N-acetylcysteine (NAC) could improve intestinal function through phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), epithelial growth factor receptor (EGFR), toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB), adenosine 5'-monophosphate-activated protein kinase (AMPK), and type I interferon (IFN) signaling pathways in a piglet model of lipopolysaccharides (LPS) challenge. Thirty-two piglets (24-day-old) were randomly allocated to one of four treatments, with eight replicates per treatment and one piglet per replicate. The experiment consisted of four treatments in a 2 × 2 factorial arrangement with two diets (supplemented with 0 or 500 mg NAC/kg diet) and saline or LPS administration. On day 20 of the trial, piglets in the LPS and LPS + NAC groups were intraperitoneally injected with 0 (saline) or 100 μg LPS/kg BW. Blood samples were obtained at 3 h and intestinal mucosae were collected at 6 h post LPS or saline injection. The growth performance was not affected by dietary NAC. LPS induced intestinal dysfunction, as indicated by: (1) reductions in the small-intestinal glutathione concentrations and plasma D-xylose levels; (2) elevations in plasma diamine oxidase activity, mucosal MMP3 mRNA levels and caspase-3 protein abundance; (3) reduced the activities of the small-intestinal mucosal maltase, sucrase and lactase. The adverse effects of LPS on porcine intestinal function and redox status were mitigated by NAC supplementation through the activation of multiple signaling pathways involving PI3K/Akt/mTOR, EGFR, TLR4/NF-κB, AMPK, and type I IFN. Our findings provide novel mechanisms for beneficial effects of NAC in protecting the intestine from inflammation in animals.
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yi
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China. houyq@aliyun.com.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chen
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Binying
authors.initials: B
authors.lastname: Ding
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.|Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, 87131, USA.
authors.forename: Chien-An Andy
authors.initials: CA
authors.lastname: Hu
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.|Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D019587:Dietary Supplements; D066246:ErbB Receptors / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000503:physiopathology; D007421:Intestine, Small / Q000187:drug effects* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D010084:Oxidation-Reduction / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D034421:Sus scrofa; D013552:Swine; D014886:Weaning
chemical_list: D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D066246:ErbB Receptors; D000111:Acetylcysteine
keywords: Intestinal function; N-Acetylcysteine; Piglets; Signaling pathway