Protective Effects Of N-acetylcysteine On Acetic Acid-induced Intestinal Injury In Piglets

The study was conducted to investigate the effects of dietary N-acetylcystine(NAC) on the acetic acid (AA)-induced intestinal injury in piglets.Eighteen healthy piglets were randomized into3treatments with6replicateseach: control, AA, and NAC groups. The control and AA groups were fed the basaldiet, whereas the NAC group was fed the basal diet supplemented with500mg/kgNAC. On day15of the trial, piglets were intrarectally administrated with10mL of10%saline (control group) or10%AA (AA and NAC groups). On d21, D-xylosewas orally administrated at the dose of0.1g/kg·BW, and1h later blood sampleswere collected.On day22of the trial, all the piglets were sacrificed to obtain liver、pancreas、intestinal mucosa for biochemical analysis.The results showed that:1. The effect of NAC on histologic assessment of colonic damage,hematological parameters and blood biochemical parameters, mucosal immunestress, intestinal barrier function of piglets induced by AA.(1) The score of AA group piglets was significantly higher than the control andNAC group piglets (P<0.05). AA clysis caused a significant reduction in gobletcells/100enterocytes (P<0.05) and lymphocytic density (P<0.05) and a increase inIEL/100enterocytes (P<0.05). However, NAC supplementation increased gobletcells/100enterocytes (P<0.05), lymphocytic density (P<0.05) and decreasedIEL/100enterocytes (P<0.05) in comparison with the AA group.(2) Compared withthe control group, AA clysis enhanced (P<0.05) WBC, W-SCC, W-LCC, AST andGGT in blood, whereas, dietary supplementation with NAC reduced W-SCC(P<0.05) and AST (P<0.01) content.(3) Compared with the control group, AAclysis increased (P<0.05) the levels of TNF-in plasma, PGE2and TGF-incolonic mucosa; NAC supplementation reversed the parameters.(4) AA clysisreduced plasma D-xylose content (P<0.1), Supplementation with NAC increasedplasma D-xylose content (P<0.1); AA piglets exhibited an increase in DAO activity in plasma (P<0.05) and decrease in duodenum (P<0.1) while NAC supplementationreduced DAO activity in plasma (P<0.05) and increase DAO activity in duodenum(P<0.1); AA clysis reduced claudin-1relative expression in colonic mucosa(P<0.05); Supplementation with NAC increased claudin-1relative expression incolonic mucosa (P<0.05). In conclusion, dietary supplementation with NAC caneffectively alleviate negative effects of AA challenge on hematological parameters,blood biochemical parameters, histologic assessment of colonic damage andeffectively alleviate the intestinal barrier function damage of piglets induced by AAclysis, which was associated with the expression of claudin-1.2. The effect of NAC on intestinal mucosal growth of piglets induced by AA.(1) AA clysis reduced the ratio of villus height to crypt depth in duodenal(P<0.05), jejunal and ileal mucosae (P<0.1), the villous surface area in duodenaland jejunal (P<0.1), while increased the crypt depth in duodenal (P<0.05) and ileal(P<0.1); dietary supplementation with NAC reversed these parameters.(2)AAclysis increased RNA/DNA (P<0.05) in jejuna, while reduced TP/DNA (P<0.05)and TP/RNA (P<0.1) in colon; NAC supplementation enhanced DNA content induodenal mucosa (P<0.05), TP/DNA (P<0.05) in jejunal and colonic mucosae,TP/RNA (P<0.1) in colonic mucosa, while reduced RNA/DNA (P<0.05) in jejunamucosa.(3) AA clysis increased relative expression of caspase-3in colonic mucosa(P<0.05), while NAC supplementation reduced relative expression of caspase-3incolonic mucosa (P<0.05).(4) NAC supplementation notedly enhanced (P<0.05)EGF mRNA level in ileum, AR and EGFR mRNA in liver and colon. In conclusion,dietary supplementation of NAC can effectively prevent apoptosis an d promote cellsurvival, which may be associated with the cell apoptosis signaling and EGFRsignaling.3. Effects of NAC on antioxidant capactiy and intestinal muscle energy statusin piglets induced by AA.(1) Antioxidant capacity: AA clysis reduced catalase (CAT) activities incolonic mucosa (P<0.05) and liver (P<0.1), super oxide dlsmutase (SOD) activities in ileal mucosa (P<0.1), and increased the activity of myeloperoxidase (MPO), theconcentrations of malondialdehyde in in plasma and colonic mucosa (P<0.05);NAC supplementation enhanced CAT activities in pancreas (P<0.05) and liver(P<0.1).(2) Intestinal muscle energy status: Compared with the control group, AApiglets, the concentrations of AMP and AMP/ATP ratio were increased (P<0.05) aswell as AEC decreased (P<0.05). However, after treatment with NAC, theconcentrations of ATP (P=0.061) and AEC (P<0.05) increased as well as AMP/ATPratio decreased (P<0.05), compared with the AA group. TAN in the NAC groupwere increased (P<0.05) compared to the control group. In conclusion, NACsupplementation could enhance antioxidant capacity and intestinal muscle energystatus of piglets to alleviate negative effects of AA challenge.In conclusion, a piglet model of ulcerative colitis (UC) was successfully builtby intrarectally administrated with10mL of10%AA. NAC supplementation couldprotect the piglet against UC may via modulating AR and EGFR signaling topromote cell growth and survival, effectively alleviating the injury of intestinalbarrier function induced by AA. NAC also improved oxidation resistance andenergy status in colonic mucosa to accelerate the recovery process.