title: N-acetylcysteine reduces inflammation in the small intestine by regulating redox, EGF and TLR4 signaling.
abstract: This study determined whether N-acetylcysteine (NAC) could affect intestinal redox status, proinflammatory cytokines, epidermal growth factor (EGF), EGF receptor (EGFR), Toll-like receptor-4 (TLR4), and aquaporin-8 in a lipopolysaccharide (LPS)-challenged piglet model. Eighteen piglets (35-day-old) were randomly allocated into one of the three treatments (control, LPS and NAC). The control and LPS groups were fed a basal diet, and the NAC group received the basal diet +500 mg/kg NAC. On days 10, 13, and 20 of the trial, the LPS- and NAC-treated piglets received intraperitoneal administration of LPS (100 μg/kg BW), whereas the control group received the same volume of saline. On days 10 and 20, venous blood samples were obtained at 3 h post LPS or saline injection. On day 21 of the trial, piglets were killed to obtain the intestinal mucosa for analysis. Compared with the control group, LPS challenge reduced (P < 0.05) the activities of superoxide dismutase, catalase, and glutathione peroxidase in jejunal mucosae, while increasing (P < 0.05) the concentrations of malondialdehyde, H2O2, O2 (·-) and the ratio of oxidized to reduced glutathione in jejunal mucosae, and concentrations of TNF-α, cortisol, interleukin-6, and prostaglandin E2 in both plasma and intestinal mucosae. These adverse effects of LPS were attenuated (P < 0.05) by NAC supplementation. Moreover, NAC prevented LPS-induced increases in abundances of intestinal HSP70 and NF-κB p65 proteins and TLR4 mRNA. NAC supplementation enhanced plasma EGF concentration and intestinal EGFR mRNA levels. Collectively, these results indicate that dietary NAC supplementation alleviates LPS-induced intestinal inflammation via regulating redox, EGF, and TLR4 signaling.
authors.affiliation: Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023, Wuhan, China. houyq777@yahoo.com.cn
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Hou
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Yi
authors.forename: Binying
authors.initials: B
authors.lastname: Ding
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Yang
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Qiu
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D019587:Dietary Supplements; D004815:Epidermal Growth Factor / Q000097:blood / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013552:Swine; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D004815:Epidermal Growth Factor; D000111:Acetylcysteine