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Antioxidant properties of mesenchymal stem cells against oxidative stress in a murine model of colitis

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Abstract

Objective

To investigate the effects of oxidative stress injury in dextran sulfate sodium (DSS)-induced colitis in mice treated with mesenchymal stem cells (MSC).

Results

Mice exposed to oral administration of 2% DSS over 7 days presented a high disease activity index and an intense colonic inflammation. Systemic infusion of MSC protected from severe colitis, reducing weight loss and diarrhea while lowering the infiltration of inflammatory cells. Moreover, toxic colitis injury increased oxidative stress. Administration of DSS decreased reduced glutathione (GSH) and superoxide dismutase (SOD) activity, and increased thiobarbituric acid-reactive substances levels in the colon. No alteration was found in catalase (CAT) and glutathione peroxidase (GPx) activity. Otherwise, MSC transplantation was able to prevent the decrease of GSH levels and SOD activity suggestive of an antioxidant property of MSC.

Conclusion

The oxidative stress is a pathomechanism underlying the pathophysiology of colitis and MSC play an important role in preventing the impairment of antioxidants defenses in inflamed colon.

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References

  • Achitei D, Ciobica A, Balan G, Gologan E, Stanciu C, Stefanescu G (2013) Different profile of peripheral antioxidant enzymes and lipid peroxidation in active and non-active inflammatory bowel disease patients. Dig Dis Sci 58:1244–1249

    Article  CAS  PubMed  Google Scholar 

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  • Anderson P, Souza-Moreira L, Morell M, Caro M, O’Valle F, Gonzalez-Rey E, Delgado M (2013) Adipose-derived mesenchymal stromal cells induce immunomodulatory macrophages which protect from experimental colitis and sepsis. Gut 62:1131–1141

    Article  CAS  PubMed  Google Scholar 

  • Browne RW, Armstrong D (1998) Reduced glutathione and glutathione disulfide. Methods Mol Biol 108:347–352

    CAS  PubMed  Google Scholar 

  • da Costa Goncalves F, Schneider N, Mello FH, Passos EP, Meurer L, Cirne-Lima E, Paz AH (2013) Characterization of acute murine dextran sodium sulfate (DSS) colitis: severity of inflammation is dependent on the DSS molecular weight and concentration. Acta Sci Veterin 41:1142

    Google Scholar 

  • da Costa Goncalves F, Schneider N, Pinto FO, Meyer FS, Visioli F, Pfaffenseller B, Lopez PL, Passos EP, Cirne-Lima EO, Meurer L, Paz AH (2014) Intravenous vs intraperitoneal mesenchymal stem cells administration: what is the best route for treating experimental colitis? World J Gastroenterol 20:18228–18239

    Article  Google Scholar 

  • Damiani CR, Benetton CA, Stoffel C, Bardini KC, Cardoso VH, Di Giunta G, Pinho RA, Dal-Pizzol F, Streck EL (2007) Oxidative stress and metabolism in animal model of colitis induced by dextran sulfate sodium. J Gastroenterol Hepatol 22:1846–1851

    Article  CAS  PubMed  Google Scholar 

  • Dieleman LA, Palmen MJ, Akol H, Bloemena E, Pena AS, Meuwissen SG, Van Rees EP (1998) Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 114:385–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernandes CG, da Rosa MS, Seminotti B, Pierozan P, Martell RW, Lagranha VL, Busanello EN, Leipnitz G, Wajner M (2013) In vivo experimental evidence that the major metabolites accumulating in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency induce oxidative stress in striatum of developing rats: a potential pathophysiological mechanism of striatal damage in this disorder. Mol Genet Metab 109:144–153

    Article  CAS  PubMed  Google Scholar 

  • Fillmann H, Kretzmann NA, San-Miguel B, Llesuy S, Marroni N, Gonzalez-Gallego J, Tunon MJ (2007) Glutamine inhibits over-expression of pro-inflammatory genes and down-regulates the nuclear factor kappaB pathway in an experimental model of colitis in the rat. Toxicology 236:217–226

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine, 4th edn. Oxford University Press, Oxford

    Google Scholar 

  • Hao L, Sun H, Wang J, Wang T, Wang M, Zou Z (2012) Mesenchymal stromal cells for cell therapy: besides supporting hematopoiesis. Int J Hematol 95:34–46

    Article  PubMed  Google Scholar 

  • Ishii T, Mann GE (2014) Redox status in mammalian cells and stem cells during culture in vitro: critical roles of Nrf2 and cystine transporter activity in the maintenance of redox balance. Redox Biol 2:786–794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kemp K, Hares K, Mallam E, Heesom KJ, Scolding N, Wilkins A (2010) Mesenchymal stem cell-secreted superoxide dismutase promotes cerebellar neuronal survival. J Neurochem 114:1569–1580

    Article  CAS  PubMed  Google Scholar 

  • Kiersztan A, Baranska A, Hapka M, Lebiedzinska M, Winiarska K, Dudziak M, Bryla J (2009) Differential action of methylselenocysteine in control and alloxan-diabetic rabbits. Chem Biol Interact 177:161–171

    Article  CAS  PubMed  Google Scholar 

  • Kruidenier L, Kuiper I, Lamers CB, Verspaget HW (2003) Intestinal oxidative damage in inflammatory bowel disease: semi-quantification, localization, and association with mucosal antioxidants. J Pathol 201:28–36

    Article  CAS  PubMed  Google Scholar 

  • Lee HJ, Oh SH, Jang HW, Kwon JH, Lee KJ, Kim CH, Park SJ, Hong SP, Cheon JH, Kim TI, Kim WH (2016) Long-term effects of bone marrow-derived mesenchymal stem cells in dextran sulfate sodium-induced murine chronic colitis. Gut Liver 10:412–419

    PubMed  PubMed Central  Google Scholar 

  • Legaki E, Roubelakis MG, Theodoropoulos GE, Lazaris A, Kollia A, Karamanolis G, Marinos E, Gazouli M (2016) Therapeutic potential of secreted molecules derived from human amniotic fluid mesenchymal stem/stroma cells in a mice model of colitis. Stem Cell Rev 12:604–612

    Article  CAS  PubMed  Google Scholar 

  • Lih-Brody L, Powell SR, Collier KP, Reddy GM, Cerchia R, Kahn E, Weissman GS, Katz S, Floyd RA, McKinley MJ, Fisher SE, Mullin GE (1996) Increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease. Dig Dis Sci 41:2078–2086

    Article  CAS  PubMed  Google Scholar 

  • Marklund S (1985) Pyrogallol autoxidation. In: Greenwald RA (ed) Handbook of methods for oxygen radical research. CRC Press, Boca Raton, pp 243–247

    Google Scholar 

  • Pravda J (2005) Radical induction theory of ulcerative colitis. World J Gastroenterol 11:2371–2384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rezaie A, Parker RD, Abdollahi M (2007) Oxidative stress and pathogenesis of inflammatory bowel disease: an epiphenomenon or the cause? Dig Dis Sci 52:2015–2021

    Article  PubMed  Google Scholar 

  • Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182:311–322

    Article  CAS  PubMed  Google Scholar 

  • Senior PV, Pritchett CJ, Sunter JP, Appleton DR, Watson AJ (1982) Crypt regeneration in adult human colonic mucosa during prolonged organ culture. J Anat 134:459–469

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shalaby SM, El-Shal AS, Abd-Allah SH, Selim AO, Selim SA, Gouda ZA, Abd El Motteleb DM, Zanfaly HE, El-Assar HM, Abdelazim S (2014) Mesenchymal stromal cell injection protects against oxidative stress in Escherichia coli-induced acute lung injury in mice. Cytotherapy 16:764–775

    Article  CAS  PubMed  Google Scholar 

  • Simovic Markovic B, Nikolic A, Gazdic M, Nurkovic J, Djordjevic I, Arsenijevic N, Stojkovic M, Lukic ML, Volarevic V (2016) Pharmacological inhibition of Gal-3 in mesenchymal stem cells enhances their capacity to promote alternative activation of macrophages in dextran sulphate sodium-induced colitis. Stem Cells Int 2016:2640746

    Article  PubMed  PubMed Central  Google Scholar 

  • Sun T, Gao GZ, Li RF, Li X, Li DW, Wu SS, Yeo AE, Jin B (2015) Bone marrow-derived mesenchymal stem cell transplantation ameliorates oxidative stress and restores intestinal mucosal permeability in chemically induced colitis in mice. Am J Transl Res 7:891–901

    CAS  PubMed  PubMed Central  Google Scholar 

  • Watanabe S, Arimura Y, Nagaishi K, Isshiki H, Onodera K, Nasuno M, Yamashita K, Idogawa M, Naishiro Y, Murata M, Adachi Y, Fujimiya M, Imai K, Shinomura Y (2014) Conditioned mesenchymal stem cells produce pleiotropic gut trophic factors. J Gastroenterol 49:270–282

    Article  CAS  PubMed  Google Scholar 

  • Wendel A (1981) Glutathione peroxidase. Methods Enzymol 77:325–333

    Article  CAS  PubMed  Google Scholar 

  • Yagi K (1998) Simple procedure for specific assay of lipid hydroperoxides in serum or plasma. Methods Mol Biol 108:107–110

    CAS  PubMed  Google Scholar 

  • Yang J, Liu XX, Fan H, Tang Q, Shou ZX, Zuo DM, Zou Z, Xu M, Chen QY, Peng Y, Deng SJ, Liu YJ (2015) Extracellular vesicles derived from bone marrow mesenchymal stem cells protect against experimental colitis via attenuating colon inflammation, oxidative stress and apoptosis. PLoS ONE 10:e0140551

    Article  PubMed  PubMed Central  Google Scholar 

  • Yavuz Y, Yuksel M, Yegen BC, Alican I (1999) The effect of antioxidant therapy on colonic inflammation in the rat. Res Exp Med 199:101–110

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Fundo de Incentivo à Pesquisa e Eventos (FIPE) of Hospital de Clínicas de Porto Alegre and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Correspondence to Fabiany da Costa Gonçalves.

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da Costa Gonçalves, F., Grings, M., Nunes, N.S. et al. Antioxidant properties of mesenchymal stem cells against oxidative stress in a murine model of colitis. Biotechnol Lett 39, 613–622 (2017). https://doi.org/10.1007/s10529-016-2272-3

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  • DOI: https://doi.org/10.1007/s10529-016-2272-3

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