title: The combination effects of acetaminophen and N-acetylcysteine on cytokines production and NF-κB activation of lipopolysaccharide-challenged piglet mononuclear phagocytes in vitro and in vivo.
abstract: Lipopolysaccharide (LPS) is a known activator of mononuclear phagocytes. LPS activates the pro-inflammatory gene expression and induces the release of mediators/cytokines by TLR4-NF-κB signaling pathway. The purpose of this study was to investigate the effects of acetaminophen (AAP) and N-acetylcysteine (NAC), individually as well as in combination on LPS-induced cytokines production and NF-κB activation in piglets. AAP (0.125-1.0mM) and NAC (0.0625-1.0mM) down-regulate the expression of cytokines and inhibit NF-κB p65 protein transfer from the cytoplasm to the nucleus in vitro. NAC enhances the inhibition action of AAP on cytokines expression in vitro. IL-6 in piglet plasma of the AAP group (mixed feed concentration of 600 mg/kg) was significantly reduced (P<0.05) at 3h after LPS-challenge as compared with the LPS control group. IL-10 also significantly reduced (P<0.05) at 24h after LPS injection. The levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10) in piglet plasma of the NAC group (mixed feeding concentration of 1200 mg/kg) were significantly lower at 3h after LPS stimulation (P<0.05). IL-10 was significantly decreased in the NAC group at 24h after LPS stimulation (P<0.05). AAP or NAC treated alone could reduce the NF-κB p65 concentration ratio. The levels of cytokines (TNF-α, IL-1β, IL-6, and IL-10) in the group with piglet plasma of AAP (mixed feed concentration of 600 mg/kg) plus NAC (mixed feeding concentration of 1200 mg/kg) group were significantly lower (P<0.05) at 3h after LPS activation. The level of IL-10 in the group with AAP plus NAC was significantly lower (P<0.05) at 24h after LPS stimulation, while the rest of the inflammatory cytokines were returned to the original levels. The NF-κB p65 concentration ratio had significantly reduced (P<0.05) when AAP and NAC were used in combination. In summary, NAC could enhance the anti-inflammatory effects of AAP both in vitro and in vivo.
authors: School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan, PR China. qiuyinsheng6405@163.com
authors: Yinsheng
authors: Y
authors: Qiu
authors: Jiawei
authors: J
authors: Zhang
authors: Yu
authors: Y
authors: Liu
authors: Hongwei
authors: H
authors: Ma
authors: Fangyuan
authors: F
authors: Cao
authors: Jun
authors: J
authors: Xu
authors: Yongqing
authors: Y
authors: Hou
authors: Lingyun
authors: L
authors: Xu
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D016207:Cytokines / Q000097:blood*; D004357:Drug Synergism; D005260:Female; D018836:Inflammation Mediators / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D034421:Sus scrofa / Q000276:immunology*; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D016753:Interleukin-10; D000082:Acetaminophen; D000111:Acetylcysteine