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This study with a piglet model determined the effects of <jats:italic>N<\/jats:italic>-acetylcysteine (NAC) on intestinal function and autophagy in response to \u03b2-CG challenge. Twenty-four 12-day-old piglets (3.44\u2009\u00b1\u20090.28\u00a0kg), which had been weaned at 7\u00a0days of age and adapted for 5\u00a0days after weaning, were randomly allocated to the control, \u03b2-CG, and \u03b2-CG\u2009+\u2009NAC groups. Piglets in the control group were fed a liquid diet containing 10% casein, whereas those in the \u03b2-CG and \u03b2-CG\u2009+\u2009NAC groups were fed the basal liquid diets containing 9.5% casein and 0.5% \u03b2-CG for 2\u00a0days. Thereafter, pigs in the \u03b2-CG\u2009+\u2009NAC group were orally administrated with 50\u00a0mg (kg BW)<jats:sup>\u22121<\/jats:sup> NAC for 3\u00a0days, while pigs in the other two groups were orally administrated with the same volume of sterile saline. NAC numerically reduced diarrhea incidence (\u2212\u200946.2%) and the concentrations of hydrogen peroxide and malondialdehyde, but increased claudin-1 and intestinal fatty-acid binding protein (iFABP) protein abundances and activities of catalase and glutathione peroxidase in the jejunum of \u03b2-CG-challenged piglets. Although \u03b2-CG challenge decreased the villus height, villus height\/crypt depth ratio, and mRNA levels of <jats:italic>claudin-1<\/jats:italic> and <jats:italic>occludin<\/jats:italic>, no significant differences were observed in these indices between the control and \u03b2-CG\u2009+\u2009NAC groups, suggesting the positive effects of NAC supplementation on intestinal mucosal barrier function. Moreover, NAC increased the concentrations of citrulline and D-xylose in the plasma, as well as the expression of genes for aquaporin (<jats:italic>AQP<\/jats:italic>) 3, <jats:italic>AQP4<\/jats:italic>, peptide transporter 1 (<jats:italic>PepT1<\/jats:italic>), sodium\/glucose co-transporter-1 (SGLT-1), potassium inwardly-rectifying channel, subfamily J, member 13 (<jats:italic>KCNJ13<\/jats:italic>), and solute carrier family 1 member 1 (<jats:italic>SLC1A1<\/jats:italic>) in the jejunum, demonstrating that NAC augmented intestinal metabolic activity and absorptive function. Remarkably, NAC decreased Atg5 protein abundance and the LC3II\/LC3I ratio (an indicator of autophagy) in the jejunum of \u03b2-CG-challenged piglets. Taken together, NAC supplementation improved intestinal function and attenuated intestinal autophagy in \u03b2-CG-challenged piglets.<\/jats:p>","DOI":"10.1038\/s41598-021-80994-2","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T11:15:21Z","timestamp":1610536521000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["N-Acetylcysteine improves intestinal function and attenuates intestinal autophagy in piglets challenged with \u03b2-conglycinin"],"prefix":"10.1038","volume":"11","author":[{"given":"Huiyun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"80994_CR1","doi-asserted-by":"publisher","first-page":"5265","DOI":"10.1021\/jf0478206","volume":"53","author":"M Golubovic","year":"2005","unstructured":"Golubovic, M., van Hateren, S. 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