PMID- 28271166 OWN - NLM STAT- MEDLINE DCOM- 20181119 LR - 20220316 IS - 1438-2199 (Electronic) IS - 0939-4451 (Linking) VI - 49 IP - 12 DP - 2017 Dec TI - N-Acetylcysteine improves intestinal function in lipopolysaccharides-challenged piglets through multiple signaling pathways. PG - 1915-1929 LID - 10.1007/s00726-017-2389-2 [doi] AB - 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-kappaB), 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 x 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 mug 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-kappaB, AMPK, and type I IFN. Our findings provide novel mechanisms for beneficial effects of NAC in protecting the intestine from inflammation in animals. FAU - Yi, Dan AU - Yi D AD - 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. FAU - Hou, Yongqing AU - Hou Y AD - 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. FAU - Xiao, Hang AU - Xiao H AD - 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. FAU - Wang, Lei AU - Wang L AD - 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. FAU - Zhang, Yue AU - Zhang Y AD - 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. FAU - Chen, Hongbo AU - Chen H AD - 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. FAU - Wu, Tao AU - Wu T AD - 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. FAU - Ding, Binying AU - Ding B AD - 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. FAU - Hu, Chien-An Andy AU - Hu CA AD - 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. AD - Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, 87131, USA. FAU - Wu, Guoyao AU - Wu G AD - 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. AD - Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA. LA - eng PT - Journal Article DEP - 20170307 PL - Austria TA - Amino Acids JT - Amino acids JID - 9200312 RN - 0 (Free Radical Scavengers) RN - 0 (Lipopolysaccharides) RN - EC 2.7.10.1 (ErbB Receptors) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/*pharmacology MH - Animals MH - Dietary Supplements MH - ErbB Receptors/metabolism MH - Free Radical Scavengers/pharmacology MH - Gene Expression Regulation/drug effects MH - Intestinal Mucosa/*drug effects/physiopathology MH - Intestine, Small/*drug effects/physiopathology MH - Lipopolysaccharides/*toxicity MH - Oxidation-Reduction/drug effects MH - Signal Transduction/*drug effects MH - *Sus scrofa MH - Swine MH - Weaning OTO - NOTNLM OT - Intestinal function OT - N-Acetylcysteine OT - Piglets OT - Signaling pathway EDAT- 2017/03/09 06:00 MHDA- 2018/11/20 06:00 CRDT- 2017/03/09 06:00 PHST- 2017/01/12 00:00 [received] PHST- 2017/01/27 00:00 [accepted] PHST- 2017/03/09 06:00 [pubmed] PHST- 2018/11/20 06:00 [medline] PHST- 2017/03/09 06:00 [entrez] AID - 10.1007/s00726-017-2389-2 [pii] AID - 10.1007/s00726-017-2389-2 [doi] PST - ppublish SO - Amino Acids. 2017 Dec;49(12):1915-1929. doi: 10.1007/s00726-017-2389-2. Epub 2017 Mar 7.