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Effect of N-acetyl cysteine on enterocyte apoptosis and intracellular signalling pathways' response to oxidative stress in weaned piglets

  • Lihui Zhu (a1), Xuan Cai (a1), Qi Guo (a1), Xiaolian Chen (a1) (a2), Suwen Zhu (a1) and Jianxiong Xu (a1)...

Abstract

N-acetyl cysteine (NAC) has been widely used for preventing reactive oxygen species-induced damage. However, little is known as to whether dietary NAC supplementation would alleviate intestinal injury in weaned piglets. The present study evaluated the effect of NAC on enterocyte apoptosis and intracellular signalling pathways' response to weaning stress. The control piglets were normally suckling, and piglets in the weaning and NAC groups were fed the basal diet and basal+NAC diet from 14 to 25 d of age, respectively. Compared with the control piglets, weaning increased cortisol concentrations (P< 0·05), decreased superoxide dismutase and glutathione peroxidase activities (P< 0·05), increased malondialdehyde content (P< 0·05) in serum and enhanced enterocyte apoptosis index (AI) and concentrations of caspase-3, caspase-8 and caspase-9 (P< 0·05). Gene expression analyses indicated that weaning induced apoptosis via Fas signalling and mitochondrial pathways in weaned piglets. Dietary NAC supplementation decreased (P< 0·05) cortisol concentrations and the AI, increased (P< 0·05) antioxidant status in serum and alleviated histopathological changes in the intestine. It also inhibited Fas, caspase-3, caspase-8 and integrin αvβ6 (αvβ6) gene expressions in the NAC-treated piglets. However, no significant decrease (P>0·10) in caspase-3, caspase-8 and caspase-9 concentrations was observed in the NAC group compared with the weaning group. In conclusion, weaning may induce enterocyte apoptosis via the activation of Fas-dependent and mitochondria-dependent apoptosis. Although NAC had no effect on caspase concentrations, it was clearly beneficial for preserving morphological integrity in weaned piglets via the regulation of cell apoptosis and the inhibition of Fas-dependent apoptosis and αvβ6 expression.

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Corresponding author

*Corresponding author: J. Xu, fax +86 21 34205767, email jxxu1962@sjtu.edu.cn

References

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1Gunther C, Neumann H, Neurath MF, et al. (2012) Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium. Gut (Epublication ahead of print version 27 June 2012).
2Cera, KR, Mahan, DC, Cross, RF, et al. (1988) Effect of age, weaning and postweaning diet on small intestinal growth and jejunal morphology in young swine. J Anim Sci 66, 574584.
3Poli, G, Leonarduzzi, G, Biasi, F, et al. (2004) Oxidative stress and cell signalling. Curr Med Chem 11, 11631182.
4Mates, JM, Perez-Gomez, C & Nunez de Castro, I (1999) Antioxidant enzymes and human diseases. Clin Biochem 32, 595603.
5Valko, M, Rhodes, CJ, Moncol, J, et al. (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160, 140.
6Tan, B, Yin, YL, Kong, XF, et al. (2010) l-Arginine stimulates proliferation and prevents endotoxin-induced death of intestinal cells. Amino Acids 38, 12271235.
7Circu, ML & Aw, TY (2012) Glutathione and modulation of cell apoptosis. Biochim Biophys Acta 1823, 17671777.
8Schoultz, I, Mckay, CM, Graepel, R, et al. (2012) Indomethacin-induced translocation of bacteria across enteric epithelia is reactive oxygen species-dependent and reduced by vitamin C. Am J Physiol Gastrointest Liver Physiol 303, G536G545.
9Zhu, LH, Zhao, KL, Chen, XL, et al. (2012) Impact of weaning and an antioxidant blend on intestinal barrier function and antioxidant status in pigs. J Anim Sci 90, 25812589.
10Oehler, R & Roth, E (2003) Regulative capacity of glutamine. Curr Opin Clin Nutr Metab Care 6, 277282.
11Higuchi, Y (2004) Glutathione depletion-induced chromosomal DNA fragmentation associated with apoptosis and necrosis. J Cell Mol Med 8, 455464.
12Mondello, S, Galuppo, M, Mazzon, E, et al. (2011) Glutamine treatment attenuates the development of organ injury induced by zymosan administration in mice. Eur J Pharmacol 658, 2840.
13Owari, M, Wasa, M, Oue, T, et al. (2012) Glutamine prevents intestinal mucosal injury induced by cyclophosphamide in rats. Pediatr Surg Int 28, 299303.
14Quadrilatero, J & Hoffman-Goetz, L (2004) N-acetyl-l-cysteine prevents exercise-induced intestinal lymphocyte apoptosis by maintaining intracellular glutathione levels and reducing mitochondrial membrane depolarization. Biochem Biophys Res Commun 319, 894901.
15Denning, TL, Takaishi, H, Crowe, S, et al. (2002) Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells. Free Radic Biol Med 33, 16411650.
16Ocal, K, Avlan, D, Cinel, I, et al. (2004) The effects of N-acetyl cysteine on oxidative stress in intestine and bacterial translocation after thermal injury. Burns 30, 778784.
17Reliene, R, Pollard, JM, Sobol, Z, et al. (2009) N-acetyl cysteine protects against ionizing radiation-induced DNA damage but not against cell killing in yeast and mammals. Mutat Res 665, 3743.
18Hou, Y, Wang, L, Zhang, W, et al. (2012) Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide. Amino Acids 43, 12331242.
19Noda, T, Iwakiri, R, Fujimoto, K, et al. (1998) Programmed cell death induced by ischemia–reperfusion in rat intestinal mucosa. Am J Physiol 274, G270G276.
20Daniel, JA, Keisler, DH, Sterle, JA, et al. (1999) Birth by caesarian section alters postnatal function of the hypothalamic–pituitary–adrenal axis in young pigs. J Anim Sci 77, 742749.
21Livak, KJ & Schmittgen, TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2( − Delta Delta C(T)) method. Methods 25, 402408.
22Koopmans, SJ, Guzik, AC, Van der Meulen, J, et al. (2006) Effects of supplemental l-tryptophan on serotonin, cortisol, intestinal integrity, and behavior in weanling piglets. J Anim Sci 84, 963971.
23Ming, J, Xie, J, Xu, P, et al. (2012) Effects of emodin and vitamin C on growth performance, biochemical parameters and two HSP70s mRNA expression of Wuchang bream (Megalobrama amblycephala Yih) under high temperature stress. Fish Shellfish Immunol 32, 651661.
24Rodriguez, CE, Shinyashiki, M, Froines, J, et al. (2004) An examination of quinone toxicity using the yeast Saccharomyces cerevisiae model system. Toxicology 201, 185196.
25Romero, FJ, Bosch-Morell, F, Romero, MJ, et al. (1998) Lipid peroxidation products and antioxidants in human disease. Environ Health Perspect 106, 12291234.
26Zhao, HD, Zhang, F, Shen, G, et al. (2010) Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway. World J Gastroenterol 16, 30023010.
27Ozyurt, B, Iraz, M, Koca, K, et al. (2006) Protective effects of caffeic acid phenethyl ester on skeletal muscle ischemia–reperfusion injury in rats. Mol Cell Biochem 292, 197203.
28Koca, K, Yurttas, Y, Cayci, T, et al. (2011) The role of preconditioning and N-acetylcysteine on oxidative stress resulting from tourniquet-induced ischemia–reperfusion in arthroscopic knee surgery. J Trauma 70, 717723.
29Aruoma, OI, Halliwell, B, Hoey, BM, et al. (1989) The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med 6, 593597.
30Song, M, Kellum, JA, Kaldas, H, et al. (2004) Evidence that glutathione depletion is a mechanism responsible for the anti-inflammatory effects of ethyl pyruvate in cultured lipopolysaccharide-stimulated RAW 264.7 cells. J Pharmacol Exp Ther 308, 307316.
31Souza, HS, Tortori, CJ, Castelo-Branco, MT, et al. (2005) Apoptosis in the intestinal mucosa of patients with inflammatory bowel disease: evidence of altered expression of FasL and perforin cytotoxic pathways. Int J Colorectal Dis 20, 277286.
32Siggers, RH & Hackam, DJ (2011) The role of innate immune-stimulated epithelial apoptosis during gastrointestinal inflammatory diseases. Cell Mol Life Sci 68, 36233634.
33Sun, Z, Wang, X, Wallen, R, et al. (1998) The influence of apoptosis on intestinal barrier integrity in rats. Scand J Gastroenterol 33, 415422.
34McCracken, BA, Spurlock, ME, Roos, MA, et al. (1999) Weaning anorexia may contribute to local inflammation in the piglet small intestine. J Nutr 129, 613619.
35Pie, S, Lalles, JP, Blazy, F, et al. (2004) Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets. J Nutr 134, 641647.
36Wang, X (2001) The expanding role of mitochondria in apoptosis. Genes Dev 15, 29222933.
37Budihardjo, I, Oliver, H, Lutter, M, et al. (1999) Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol 15, 269290.
38Riedl, SJ & Shi, Y (2004) Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol 5, 897907.
39Takahashi, A, Masuda, A, Sun, M, et al. (2004) Oxidative stress-induced apoptosis is associated with alterations in mitochondrial caspase activity and Bcl-2-dependent alterations in mitochondrial pH (pHm). Brain Res Bull 62, 497504.
40Malassagne, B, Ferret, PJ, Hammond, R, et al. (2001) The superoxide dismutase mimetic MnTBAP prevents Fas-induced acute liver failure in the mouse. Gastroenterology 121, 14511459.
41Chiba, T, Takahashi, S, Sato, N, et al. (2005) Fas-mediated apoptosis is modulated by intracellular glutathione in human T cells. Eur J Immunol 26, 11641169.
42Blanco-Mezquita, JT, Hutcheon, AE, Stepp, MA, et al. (2011) αVβ6 integrin promotes corneal wound healing. Invest Ophthalmol Vis Sci 52, 85058513.
43Bates, RC (2005) Colorectal cancer progression: integrin alphavbeta6 and the epithelial-mesenchymal transition (EMT). Cell Cycle 4, 13501352.
44Knight, PA, Wright, SH, Brown, JK, et al. (2002) Enteric expression of the integrin alpha(v)beta(6) is essential for nematode-induced mucosal mast cell hyperplasia and expression of the granule chymase, mouse mast cell protease-1. Am J Pathol 161, 771779.
45Cera, K, Mahan, D, Cross, R, et al. (1988) Effect of age, weaning and postweaning diet on small intestinal growth and jejunal morphology in young swine. J Anim Sci 66, 574584.
46Zhao-Yang, Z, Ke-Sen, X, Qing-Si, H, et al. (2008) Signaling and regulatory mechanisms of integrin alphavbeta6 on the apoptosis of colon cancer cells. Cancer Lett 266, 209215.
47Hung, WY, Huang, KH, Wu, CW, et al. (2012) Mitochondrial dysfunction promotes cell migration via reactive oxygen species-enhanced β5-integrin expression in human gastric cancer SC-M1 cells. Biochim Biophys Acta 1820, 11021110.
48Wang, B, Dolinski, BM, Kikuchi, N, et al. (2007) Role of alphavbeta6 integrin in acute biliary fibrosis. Hepatology 46, 14041412.
49Horan, GS, Wood, S, Ona, V, et al. (2008) Partial inhibition of integrin αvβ6 prevents pulmonary fibrosis without exacerbating inflammation. Am J Respir Crit Care Med 177, 5665.

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Effect of N-acetyl cysteine on enterocyte apoptosis and intracellular signalling pathways' response to oxidative stress in weaned piglets

  • Lihui Zhu (a1), Xuan Cai (a1), Qi Guo (a1), Xiaolian Chen (a1) (a2), Suwen Zhu (a1) and Jianxiong Xu (a1)...

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