Protective effects of N-acetylcysteine against liver injury in rats with severe acute pancreatitis

Abstract

AIM:To investigate the role of nuclear factor-kappa B(NF-κB)activation in liver injury in rats with severe acute pancreatitis(SAP),and to explore the protective effect of N-acetylcysteine(NAC)against SAP-associated liver injury in rats.METHODS:Forty-two Wistar male rats were divided into sham operation group(SO,n = 6),SAP group(n = 18),and SAP + NAC group(NAC,300 mg/kg body wt,n = 18).SO group underwent laparotomy only.SAP model was established by retrograde injection of 50 g/L so-dium taurocholate into the bili-pancreatic duct in Wistar rats.SAP + NAC group were given NAC 300 mg/kg body weight intaperitoneally 2 h before SAP model was established.Rats were sacrificed at 3,6 and 12 h after operation.The liver and pancreas tissues were obtained to observe their pathological changes with light microscopy.The levels of serum ALT and AST were determined at three time points(8 rats for each time point).The expression of TNF-α mRNA was detected by reverse transcription polymerase chain reaction(RT-PCR).The activ-ity of NF-κB in liver was examined by immuno-histochemical methods.RESULTS:The levels of serum ALT and AST increased significantly in SAP group as com-pared with those in SO group at 3,6 and 12 h(ALT:186.67 ± 27.28,321.17 ± 56.14,492.50 ± 69.77 vs 36.83 ± 7.02;AST:255.50 ± 44.15,343.17 ± 43.70,425.33 ± 58.37 vs 41.67 ± 5.35;P 0.05 or 0.01).The level of TNF-α mRNA in SAP group was significantly higher than that in SO group at 3,6 and 12 h(0.37 ± 0.03,0.77 ± 0.04,0.54 ± 0.04 vs 0.24 ± 0.03;P 0.05 or 0.01).The activity of NF-κB was also higher in SAP group than that in SO group at 3 or 6 h(51.95 ± 4.76,24.67 ± 4.93 vs 9.33 ± 2.05;P 0.01 or 0.05).Liver and pan-creas pathological damages were more severe in SAP group than those in SO group under light microscope.In SAP + NAC group,the levels of serum ALT and AST(143.67 ± 16.62,203.33 ± 25.41,301.17 ± 26.82;136.33 ± 26.27,221.50 ± 38.31,310.50 ± 38.17)decreased significantly in comparison with those in SAP group(P 0.05 or 0.01),and the expression of TNF-α mRNA was significantly lower than that in SAP group at the three time points(0.25 ± 0.03,0.50 ± 0.05,0.43 ± 0.03,P 0.05 or 0.01).The activity of NF-κB in SAP + NAC group was lower than that in SAP group at 3 or 6 h(37.60 ± 6.37,12.88 ± 2.66,P 0.05).CONCLUSION:NF-κB activation and TNF-α mRNA up-regulation involve in the pathogen-esis of liver injury in SAP rats.NAC at a dose of 300 mg/kg can alleviate the pathological dam-age to liver,and its mechanism might relate to inhibition of NF-κB activation and reduction of cytokines such as TNF-α.