Study On Enhancing Efficacy And Reducing Toxicity Of Combined Acetaminophe And N-acetylcysteine On Weaned Pigs Subjected To An Immunological Stress

The pathogen infection or vaccination caused piglet immunological stress is very common in production,Bring great harm to industry,but lack effective control measures. This paper will discusses the acetaminophen joint acetylcysteine alleviate the piglet immunological stress attenuated..Experiment 1 was conducted in vitro to investigate the effects of acetaminophen and combination of acetaminophen and N-acetylcysteine on the cell viability of swine peripheral blood mononuclear cells (PBMC), and the anti-inflammatory activities of the two drugs alone and combination on the release of inflammatory mediators and pro -inflammatory cytokines induced by lipopolysaccharide in vitro. Cell viability was determined by MTT assay, and TNF-α, IL-6, COX-2 and PGE2 levels in the supernatants of the PBMC cultures were measured by ELISA assay. The data indicated that cell viability was not effected by the N-acetylcysteine at low concentration treatment (0.25, 0.5 and 1mM), but was increased by high concentration treatment (2 and 5 mM). Both N-acetylcysteine and acetaminophen inhibit the release of inflammatory mediators and pro-inflammatory cytokines. The IC90 values of TNF-α, IL-6, COX-2 and PGE2 were 1.081,1,523,0.439and 0.821 mM respectively for N-acetylcysteine treatment, and were 1.419,1.987,0.362 and 0.438 mM respectively for acetaminophen treatment. Addition of 0.5 or 1 mM N-acetylcysteine to acetaminophen enhanced the inhibition actions of TNF-α, IL-6, COX-2 and PGE2. The results indicate that combination of acetaminophen and N-acetylcysteine will exhibit a potentiation of synergistic anti- inflammatory effect.Experiment 2 was conducted in vivo to evaluate the anti-immuno -logical stress effects of acetaminophe (AAP),N-acetylcysteine (NAC) and their interaction, an immunological stress model was established through intraperitoneal injecting with E. coli lipopolysaccharide (LPS). A total of 30 crossbred weaned pigs (Duroc×Large White×Landrace, average initial BW of 11--12 kg). Pigs were allotted to five treatments including:①nonchallenged control;②challenged control;③NAC arginine (500 mg/kg NAC);④AAP arginine (500 mg/kg AAP);⑤AAP+NAC arginine (500 mg/kg AAP+NAC).On d 1 and d 7 weighing and accurate records daily intake.On d 7 pigs in the②to⑤groups were injected intraperitoneally with 100μg/kg bw LPS,whereas pigs in①group were injected with an equivalent amount of sterile saline. Blood samples were collected at 3 and 24 h post-challenge for furthur analysis. The result indicated that there were significantly effects in peripheral hematology ( WBC,NEU,LYM,MONO,RBC,HGB,PLT) and biochemistry( AST,ALP,TBIL,BUN,CREA,TP,ALB,GLU).The Results showed that LPS induced piglet physiology reaction severely, AAP can alleviate LPS challenge on pigs temperature, NAC can alleviate vomiting, sleepiness and tremor, and also improve the production performance. The combination diets have certain synergistic. Aceta -minophen significantly increased liver and kidney toxicity by LPS induced. There was a significantly ameliorative regulation by combined with N-acetylcysteine. Accordingly, we concluded that combination of acetaminophen and N-acetylcysteine will ameliorate the toxicity of hematology and blood biochemistry when piglets exposed to LPS.In a conclusion, study on enhancing efficacy and reducing toxicity of combined acetaminophe and N-acetylcysteine on weaned pigs subjected to an immunological Stress.