Treatment with selenium-enriched Saccharomyces cerevisiae UFMG A-905 partially ameliorates mucositis induced by 5-fluorouracil in mice
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Gastrointestinal mucositis is a major problem associated with cancer therapy. To minimize these deleterious effects, simultaneous administration of antioxidant components, such as selenium, can be considered. There is a growing interest in the use of yeasts because they are able to convert inorganic selenium into selenomethionine. In the present study, oral administration of Saccharomyces cerevisiae UFMG A-905 enriched with selenium was evaluated as an alternative in minimizing the side effects of 5FU-induced mucositis in mice.
Mice body weight, food consumption, faeces consistency and the presence of blood in faeces were assessed daily during experimental mucositis induced by 5-fluorouracil (5FU). Blood was used for intestinal permeability determination, and small intestine for oxidative stress, immunological and histopathological examination.
The increased intestinal permeability observed with mucositis induction was partially reverted by S. cerevisiae and selenium-enriched yeast. Both treatments were able to reduce myeloperoxidase activity, but only selenium-enriched yeast reduced eosinophil peroxidase activity. CXCL1/KC levels, histopathological tissue damage and oxidative stress (lipid peroxidation and nitrite production) in the small intestine were reduced by both treatments; however, this reduction was always higher when treatment with selenium-enriched yeast was evaluated.
Results of the present study showed that the oral administration of S. cerevisiae UFMG A-905 protected mice against mucositis induced by 5-FU, and that this effect was potentiated when the yeast was enriched with selenium.
KeywordsProbiotics Saccharomyces cerevisiae UFMG A-905 Selenium Selenium-enriched yeast Mucositis 5-Fluorouracil
This work was supported by grants from the Brazilian National Council for Scientific and Technological Development (CNPq), the Ministry of Science and Technology (MICT) and the Foundation for Research Support of the State of Minas Gerais (FAPEMIG—APQ-00593-14), Brazil. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. BAAP was the recipient of a Ph.D.’s fellowship from CNPq. Professors JIAL, VNC, DAS, JRN and FSM are CNPq fellowship holders.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Animal experiments were carried out according to the standards set forth by the Brazilian National Council for Control of Animal Experimentation (CONCEA). This study was approved under Protocol no. 186/2012 by the Ethics Committee on the Use of Animals (CEUA/UFMG).
- 1.Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) (2014) Clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 120(10):1453–1461CrossRefGoogle Scholar
- 3.Justino PF, Melo LF, Nogueira AF, Costa JV, Silva LM, Santos CM, Mendes WO, Costa MR, Franco AX, Lima AA, Ribeiro RA, Souza MH, Soares PM (2014) Treatment with Saccharomyces boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in 5-fluorouracil-induced intestinal mucositis in mice. Br J Nutr 111(9):1611–1621CrossRefGoogle Scholar
- 5.Li C, Zhou HM (2011) The role of manganese superoxide dismutase in inflammation defense. Enzyme Res 2011:387176Google Scholar
- 10.Bastos RW, Pedroso SH, Vieira AT, Moreira LM, França CS, Cartelle CT, Arantes RM, Generoso SV, Cardoso VN, Neves MJ, Nicoli JR, Martins FS (2016) Saccharomyces cerevisiae UFMG A-905 treatment reduces intestinal damage in a murine model of irinotecan-induced mucositis. Benef Microbes 7(4):549–557CrossRefGoogle Scholar
- 12.Generoso SV, Viana M, Santos R, Martins FS, Machado JA, Arantes RM, Nicoli JR, Correia MI, Cardoso VN (2010) Saccharomyces cerevisiae strain UFMG 905 protects against bacterial translocation, preserves gut barrier integrity and stimulates the immune system in a murine intestinal obstruction model. Arch Microbiol 192(6):477–484CrossRefGoogle Scholar
- 14.Martins FS, Rodrigues AC, Tiago FC, Penna FJ, Rosa CA, Arantes RM, Nardi RM, Neves MJ, Nicoli JR (2007) Saccharomyces cerevisiae strain 905 reduces the translocation of Salmonella enterica serotype Typhimurium and stimulates the immune system in gnotobiotic and conventional mice. J Med Microbiol 56(3):352–359CrossRefGoogle Scholar
- 15.Martins FS, Elian SD, Vieira AT, Tiago FC, Martins AK, Silva FC, Souza EL, Sousa LP, Araújo HR, Pimenta PF, Bonjardim CA, Arantes RM, Teixeira MM, Nicoli JR (2011) Oral treatment with Saccharomyces cerevisiae strain UFMG 905 modulates immune responses and interferes with signal pathways involved in the activation of inflammation in a murine model of typhoid fever. Int J Med Microbiol 301(4):359–364CrossRefGoogle Scholar
- 18.Zamith-Miranda D, Palma ML, Matos GM, Schiebel JG, Maya-Monteiro CM, Aronovich M, Bozza PT, Bozza FA, Nimrichter L, Montero-Lomeli M, Marques ETA Jr, Martins FS, Douradinha B (2016) Lipid droplet levels vary heterogeneously in response to simulated gastrointestinal stresses in different probiotic Saccharomyces cerevisiae strains. J Funct Foods 21:193–200CrossRefGoogle Scholar
- 21.Andrade ME, Santos RD, Soares AD, Costa KA, Fernandes SO, de Souza CM, Cassali GD, de Souza AL, Faria AM, Cardoso VN (2016) Pretreatment and treatment with l-arginine attenuate weight loss and bacterial translocation in dextran sulfate sodium colitis. JPEN J Parenter Enteral Nutr 40(8):1131–1139CrossRefGoogle Scholar
- 26.Chen SM, Swilley S, Bell R, Rajanna S, Reddy SL, Rajanna B (2000) Lead induced alterations in nitrite and nitrate levels in different regions of the rat brain. Comp Biochem Physiol C Toxicol Pharmacol 125(3):315–323Google Scholar
- 28.Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275Google Scholar
- 32.da Silva JF, Peluzio JM, Prado G, Madeira JE, Silva MO, de Morais PB, Rosa CA, Pimenta RS, Nicoli JR (2015) Use of probiotics to control aflatoxin production in peanut grains. ScientificWorldJournal 2015:959138Google Scholar
- 33.Justino PF, Melo LF, Nogueira AF, Morais CM, Mendes WO, Franco AX, Souza EP, Ribeiro RA, Souza MH, Soares PM (2015) Regulatory role of Lactobacillus acidophilus on inflammation and gastric dysmotility in intestinal mucositis induced by 5-fluorouracil in mice. Cancer Chemother Pharmacol 75(3):559–567CrossRefGoogle Scholar
- 35.Du XX, Doerschuk CM, Orazi A, Williams DA (1994) A bone marrow stromal-derived growth factor, interleukin-11, stimulates recovery of small intestinal mucosal cells after cytoablative therapy. Blood 83(1):33–37Google Scholar
- 37.Whitford EJ, Cummins AG, Butler RN, Prisciandaro LD, Fauser JK, Yazbeck R, Lawrence A, Cheah KY, Wright TH, Lymn KA, Howarth GS (2009) Effects of Streptococcus thermophilus TH-4 on intestinal mucositis induced by the chemotherapeutic agent 5-Fluorouracil (5-FU). Cancer Biol Ther 8(6):505–511CrossRefGoogle Scholar
- 43.Vieira AT, Fagundes CT, Alessandri AL, Castor MG, Guabiraba R, Borges VO, Silveira KD, Vieira EL, Gonçalves JL, Silva TA, Deruaz M, Proudfoot AE, Sousa LP, Teixeira MM (2009) Treatment with a novel chemokine-binding protein or eosinophil lineage-ablation protects mice from experimental colitis. Am J Pathol 175(6):2382–2391CrossRefGoogle Scholar
- 47.Ammendrup A, Maillard A, Nielsen K, Aabenhus Andersen N, Serup P, Dragsbaek Madsen O, Mandrup-Poulsen T, Bonny C (2000) The c-Jun amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic beta-cells. Diabetes 49(9):1468–1476CrossRefGoogle Scholar