Polysaccharide Fraction from Campomanesia adamantium and Campomanesia pubescens Attenuates 5-Fluorouracil-Induced Intestinal Mucosal Inflammation in Mice

References

• Devlin EJ, Denson LA, Whitford HS. Cancer treatment side effects: A meta-analysis of the relationship between response expectancies and experience. J Pain Symptom Manage. 2017;54(2):245–58.e2. doi: 10.1016/j.jpainsymman.2017.03.017.
   PubMed Web of Science ®Google Scholar
• Sougiannis AT, VanderVeen BN, Davis JM, Fan D, Murphy EA. Understanding chemotherapy-induced intestinal mucositis and strategies to improve gut resilience. Am J Physiol Gastrointest Liver Physiol. 2021;320(5):G712–G719. doi: 10.1152/ajpgi.00380.2020.
   PubMed Web of Science ®Google Scholar
• Sougiannis AT, VanderVeen BN, Enos RT, Velazquez KT, Bader JE, Carson M, Chatzistamou I, Walla M, Pena MM, Kubinak JL, et al. Impact of 5 fluorouracil chemotherapy on gut inflammation, functional parameters, and gut microbiota. Brain Behav Immun. 2019;80:44–55. doi: 10.1016/j.bbi.2019.02.020.
   PubMed Web of Science ®Google Scholar
• Gibson RJ, Keefe DMK, Lalla RV, Bateman E, Blijlevens N, Fijlstra M, King EE, Stringer AM, van der Velden WJFM, Yazbeck R, Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO), et al. Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Support Care Cancer. 2013;21(1):313–26. doi: 10.1007/s00520-012-1644-z.
   PubMed Web of Science ®Google Scholar
• Kciuk M, Marciniak B, Kontek R. Irinotecan—still an important player in cancer chemotherapy: A comprehensive overview. IJMS. 2020;21(14):4919. doi: 10.3390/ijms21144919.
   Web of Science ®Google Scholar
• Dahlgren D, Sjöblom M, Hellström PM, Lennernäs H. Chemotherapeutics-induced intestinal mucositis: Pathophysiology and potential treatment strategies. Front Pharmacol. 2021;12:681417. doi: 10.3389/fphar.2021.681417.
   PubMed Web of Science ®Google Scholar
• Ghafouri-Fard S, Abak A, Tondro Anamag F, Shoorei H, Fattahi F, Javadinia SA, Basiri A, Taheri M. 5-Fluorouracil: A narrative review on the role of regulatory mechanisms in driving resistance to this chemotherapeutic agent. Front Oncol. 2021;11:658636. doi: 10.3389/fonc.2021.658636.
   PubMed Web of Science ®Google Scholar
• Hamouda N, Sano T, Oikawa Y, Ozaki T, Shimakawa M, Matsumoto K, Amagase K, Higuchi K, Kato S. Apoptosis, dysbiosis and expression of inflammatory cytokines are sequential events in the development of 5-fluorouracil-induced intestinal mucositis in mice. Basic Clin Pharmacol Toxicol. 2017; 121(3):159–68. doi: 10.1111/bcpt.12793.
   PubMed Web of Science ®Google Scholar
• Rodríguez-Caballero A, Torres-Lagares D, Robles-García M, Pachón-Ibáñez J, González-Padilla D, Gutiérrez-Pérez JL. Cancer treatment-induced oral mucositis: a critical review. Int J Oral Maxillofac Surg. 2012;41(2):225–38. doi: 10.1016/j.ijom.2011.10.011.
   PubMed Web of Science ®Google Scholar
• Patankar JV, Becker C. Cell death in the gut epithelium and implications for chronic inflammation. Nat Rev Gastroenterol Hepatol. 2020;17(9):543–56. doi: 10.1038/s41575-020-0326-4.
   PubMed Web of Science ®Google Scholar
• Fine RL, Manfredo Vieira S, Gilmore MS, Kriegel MA. Mechanisms and consequences of gut commensal translocation in chronic diseases. Gut Microbes. 2020;11(2):217–30. doi: 10.1080/19490976.2019.1629236.
   PubMed Web of Science ®Google Scholar
• Rodrigues-Oliveira L, Kowalski LP, Santos M, Marta GN, Bensadoun R-J, Martins MD, Lopes MA, Castro GD, William WN, Chaves ALF, et al. Direct costs associated with the management of mucositis: A systematic review. Oral Oncol. 2021;118:105296. doi: 10.1016/j.oraloncology.2021.105296.
   PubMed Web of Science ®Google Scholar
• Gopinath V, Saravanan S, Al-Maleki AR, Ramesh M, Vadivelu J. A review of natural polysaccharides for drug delivery applications: Special focus on cellulose, starch and glycogen. Biomed Pharmacother. 2018;107:96–108. doi: 10.1016/j.biopha.2018.07.136.
   PubMed Web of Science ®Google Scholar
• Hou C, Chen L, Yang L, Ji X. An insight into anti-inflammatory effects of natural polysaccharides. Int J Biol Macromol. 2020;153:248–55. doi: 10.1016/j.ijbiomac.2020.02.315.
   PubMed Web of Science ®Google Scholar
• Allawadhi P, Singh V, Govindaraj K, Khurana I, Sarode LP, Navik U, Banothu AK, Weiskirchen R, Bharani KK, Khurana A. Biomedical applications of polysaccharide nanoparticles for chronic inflammatory ­disorders: Focus on rheumatoid arthritis, diabetes and organ fibrosis. Carbohydr Polym. 2022;281:118923. doi: 10.1016/j.carbpol.2021.118923.
   PubMed Web of Science ®Google Scholar
• Du Y, Wan H, Huang P, Yang J, He Y. A critical review of astragalus polysaccharides: From therapeutic mechanisms to pharmaceutics. Biomed Pharmacother. 2022;147:112654. doi: 10.1016/j.biopha.2022.112654.
   PubMed Web of Science ®Google Scholar
• Wang Y, Zhu H, Wang X, Yu Y, Xie J. Natural food polysaccharides ameliorate inflammatory bowel disease and its mechanisms. Foods. 2021;10(6):1288. doi: 10.3390/foods10061288.
   PubMed Web of Science ®Google Scholar
• Zuo T, Cao L, Xue C, Tang Q-J. Dietary squid ink polysaccharide induces goblet cells to protect small intestine from chemotherapy induced injury. Food Funct. 2015;6(3):981–6. doi: 10.1039/C4FO01191K.
   PubMed Web of Science ®Google Scholar
• Koizumi R, Azuma K, Izawa H, Morimoto M, Ochi K, Tsuka T, Imagawa T, Osaki T, Ito N, Okamoto Y, et al. Oral administration of surface-deacetylated chitin nanofibers and chitosan inhibit 5-fluorouracil-induced intestinal mucositis in mice. IJMS. 2017;18(2):279. doi: 10.3390/ijms18020279.
   Web of Science ®Google Scholar
• Cai B, Wan P, Sun H, Chen D, Chen H, Chen X, Pan J. Protective effects of enteral nutrition supplemented with crassostrea hongkongensis polysaccharides against 5-fluorouracil-induced intestinal mucosal damage in rats. J Med Food. 2018;21(4):348–55. doi: 10.1089/jmf.2017.4025.
   PubMed Web of Science ®Google Scholar
• Ying M, Zheng B, Yu Q, Hou K, Wang H, Zhao M, Chen Y, Xie J, Nie S, Xie M. Ganoderma atrum polysaccharide ameliorates intestinal mucosal dysfunction associated with autophagy in immunosuppressed mice. Food Chem Toxicol. 2020;138:111244. doi: 10.1016/j.fct.2020.111244.
   PubMed Web of Science ®Google Scholar
• Bai Y, Huang F, Zhang R, Dong L, Jia X, Liu L, Yi Y, Zhang M. Longan pulp polysaccharides relieve intestinal injury in vivo and in vitro by promoting tight junction expression. Carbohydr Polym. 2020;229:115475. doi: 10.1016/j.carbpol.2019.115475.
   PubMed Web of Science ®Google Scholar
• Karaca H, Bozkurt O, Ozaslan E, Baldane S, Berk V, Inanc M, Duran AO, Dikilitas M, Er O, Ozkan M. Positive effects of oral β-glucan on mucositis and leukopenia in colorectal cancer patients receiving adjuvant FOLFOX-4 combination chemotherapy. Asian Pac J Cancer Prev. 2014;15(8):3641–4. doi: 10.7314/APJCP.2014.15.8.3641.
   PubMedGoogle Scholar
• Zhang Q-Y, Wang F-X, Jia K-K, Kong L-D. Natural product interventions for chemotherapy and radiotherapy-induced side effects. Front Pharmacol. 2018;6;9:1253. doi: 10.3389/fphar.2018.01253.
   Web of Science ®Google Scholar
• Wang C, Yang S, Gao L, Wang L, Cao L. Carboxymethyl pachyman (CMP) reduces intestinal mucositis and regulates the intestinal microflora in 5-fluorouracil-treated CT26 tumour-bearing mice. Food Funct. 2018;9(5):2695–704. doi: 10.1039/C7FO01886J.
   PubMed Web of Science ®Google Scholar
• Safonova EA, Lopatina KA, Razina TG, Zueva EP, Sadrikina LA, Gur’ev AM, Belousov MV. Correction of damaging effects of cisplatin-containing polychemotherapy on the intestinal epithelium with Tussilago farfara L. polysaccharides. Bull Exp Biol Med. 2019;167(5):616–20. doi: 10.1007/s10517-019-04582-1.
   PubMed Web of Science ®Google Scholar
• Abboud KY, da Luz BB, Dallazen JL, Werner MdP, Cazarin CBB, Maróstica Junior MR, Iacomini M, Cordeiro LMC. Gastroprotective effect of soluble dietary fibres from yellow passion fruit (Passiflora edulis f. flavicarpa) peel against ethanol-induced ulcer in rats. J Funct Foods. 2019;54:552–8. doi: 10.1016/j.jff.2019.02.003.
   Web of Science ®Google Scholar
• Colodel C, Vriesmann LC, de Oliveira Petkowicz CL. Cell wall polysaccharides from Ponkan mandarin (Citrus reticulata Blanco cv. Ponkan) peel. Carbohydr Polym. 2018;195:120–7. doi: 10.1016/j.carbpol.2018.04.066.
   PubMed Web of Science ®Google Scholar
• Schneider VS, Bark JM, Winnischofer SMB, Dos Santos EF, Iacomini M, Cordeiro LMC. Dietary fibres from guavira pomace, a co-product from fruit pulp industry: Characterization and cellular antioxidant activity. Food Res Int. 2020;132:109065. doi: 10.1016/j.foodres.2020.109065.
   PubMed Web of Science ®Google Scholar
• Vallilo MI, Lamardo LCA, Gaberlotti ML, Oliveira ED, Moreno PRH. Composição química dos frutos de Campomanesia adamantium (Cambessédes) O.Berg. Ciênc Tecnol Aliment. 2006;26(4):805–10. doi: 10.1590/S0101-20612006000400015.
   Google Scholar
• Mariott M, Mariano LNB, Boeing T, Cechinel Zanchett CC, Salamanca E, Bella Cruz A, Giménez A, Cechinel Filho V, Silva LM. Preparations from Campomanesia reitziana reduce the gastrointestinal motility and castor oil‐induced diarrhea in a non‐opioid and non‐dopaminergic pathway in mice and display antimicrobial activity in vitro. Neurogastroenterol Motil. 2022;34(2):e14277. doi: 10.1111/nmo.14277.
   PubMed Web of Science ®Google Scholar
• Lescano CH, de Oliveira IP, Zaminelli T, Baldivia D da S, da Silva LR, Napolitano M, Silvério CBM, Lincopan N, Sanjinez-Argandoña EJ. Campomanesia adamantium peel extract in antidiarrheal activity: The ability of inhibition of heat-stable enterotoxin by polyphenols. PLoS One. 2016;11(10):e0165208. doi: 10.1371/journal.pone.0165208.
   PubMed Web of Science ®Google Scholar
• Mulinari Turin de Oliveira N, Barbosa da Luz B, Schneider VS, Barbosa da Costa Filho H, Sérgio de Araujo Sousa P, Fernanda de Paula Werner M, Henrique Loiola Ponte de Souza M, Almeida Rocha J, Antonio Duarte Nicolau L, Mach Côrtes Cordeiro L, et al. Dietary polysaccharides from guavira pomace, a co-product from the fruit pulp industry, display therapeutic application in gut disorders. Food Res Int. 2022;156:111291. doi: 10.1016/j.foodres.2022.111291.
   PubMed Web of Science ®Google Scholar
• Suchitra AD, Dkhar SA, Shewade DG, Shashindran CH. Relative efficacy of some prokinetic drugs in morphine-induced gastrointestinal transit delay in mice. World J Gastroenterol. 2003;9(4):779–83. doi: 10.3748/wjg.v9.i4.779.
   PubMed Web of Science ®Google Scholar
• Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54. doi: 10.1006/abio.1976.9999.
   PubMed Web of Science ®Google Scholar
• Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 1968;25(1):192–205. doi: 10.1016/0003-2697(68)90092-4.
   PubMed Web of Science ®Google Scholar
• Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. J Biol Chem. 1974;249(22):7130–9. doi: 10.1016/S0021-9258(19)42083-8.
   PubMed Web of Science ®Google Scholar
• Gao R, Yuan Z, Zhao Z, Gao X. Mechanism of pyrogallol autoxidation and determination of superoxide dismutase enzyme activity. Bioelectrochemistry Bioenerg. 1998;45(1):41–5. doi: 10.1016/S0302-4598(98)00072-5.
   Web of Science ®Google Scholar
• Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982;78(3):206–9. doi: 10.1111/1523-1747.ep12506462.
   PubMed Web of Science ®Google Scholar
• Boeing T, Gois MB, de Souza P, Somensi LB, Sant Ana DMG, da Silva LM. Irinotecan-induced intestinal mucositis in mice: a histopathological study. Cancer Chemother Pharmacol. 2021;87(3):327–36. doi: 10.1007/s00280-020-04186-x.
   PubMed Web of Science ®Google Scholar
• Focaccetti C, Bruno A, Magnani E, Bartolini D, Principi E, Dallaglio K, Bucci EO, Finzi G, Sessa F, Noonan DM, et al. Effects of 5-Fluorouracil on morphology, cell cycle, proliferation, apoptosis, autophagy and ROS production in endothelial cells and cardiomyocytes. PLoS One. 2015;10(2):e0115686. doi: 10.1371/journal.pone.0115686.
   PubMed Web of Science ®Google Scholar
• Arends J. How to feed patients with gastrointestinal mucositis. Curr Opin Support Palliat Care. 2018;12(2):168–73. doi: 10.1097/SPC.0000000000000345.
   PubMed Web of Science ®Google Scholar
• Chang C-T, Ho T-Y, Lin H, Liang J-A, Huang H-C, Li C-C, Lo H-Y, Wu S-L, Huang Y-F, Hsiang C-Y. 5-Fluorouracil induced intestinal mucositis via nuclear factor-κB activation by transcriptomic analysis and in vivo bioluminescence imaging. PLoS One. 2012;7(3):e31808. doi: 10.1371/journal.pone.0031808.
   PubMed Web of Science ®Google Scholar
• Justino PFC, Melo LFM, Nogueira AF, Morais CM, Mendes WO, Franco AX, Souza EP, Ribeiro RA, Souza MHLP, Soares PMG. Regulatory role of Lactobacillus acidophilus on inflammation and gastric dysmotility in intestinal mucositis induced by 5-fluorouracil in mice. Cancer Chemother Pharmacol. 2015;75(3):559–67. doi: 10.1007/s00280-014-2663-x.
   PubMed Web of Science ®Google Scholar
• Melo MLP, Brito GAC, Soares RC, Carvalho SBLM, Silva JV, Soares PMG, Vale ML, Souza MHLP, Cunha FQ, Ribeiro RA. Role of cytokines (TNF-α, IL-1β and KC) in the pathogenesis of CPT-11-induced intestinal mucositis in mice: Effect of pentoxifylline and thalidomide. Cancer Chemother Pharmacol. 2008;61(5):775–84. doi: 10.1007/s00280-007-0534-4.
   PubMed Web of Science ®Google Scholar
• Logan RM, Stringer AM, Bowen JM, Gibson RJ, Sonis ST, Keefe DMK. Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered? Cancer Chemother Pharmacol. 2009;63(2):239–51. doi: 10.1007/s00280-008-0732-8.
   PubMed Web of Science ®Google Scholar
• Soares PMG, Mota JMSC, Gomes AS, Oliveira RB, Assreuy AMS, Brito GAC, Santos AA, Ribeiro RA, Souza MHLP. Gastrointestinal dysmotility in 5-fluorouracil-induced intestinal mucositis outlasts inflammatory process resolution. Cancer Chemother Pharmacol. 2008;63(1):91–8. doi: 10.1007/s00280-008-0715-9.
   PubMed Web of Science ®Google Scholar
• Shen S-R, Chen W-J, Chu H-F, Wu S-H, Wang Y-R, Shen T-L. Amelioration of 5-fluorouracil-induced intestinal mucositis by Streptococcus thermophilus ST4 in a mouse model. PLoS One. 2021;16(7):e0253540. doi: 10.1371/journal.pone.0253540.
   PubMed Web of Science ®Google Scholar
• Sangild PT, Shen RL, Pontoppidan P, Rathe M. Animal models of chemotherapy-induced mucositis: Translational relevance and challenges. Am J Physiol Gastrointest Liver Physiol. 2018;1;314(2):G231-G246. doi: 10.1152/ajpgi.00204.2017.
   Web of Science ®Google Scholar
• Li H-L, Lu L, Wang X-S, Qin L-Y, Wang P, Qiu S-P, Wu H, Huang F, Zhang B-B, Shi H-L, et al. Alteration of gut microbiota and inflammatory cytokine/chemokine profiles in 5-fluorouracil induced intestinal mucositis. Front Cell Infect Microbiol. 2017;7:455. doi: 10.3389/fcimb.2017.00455.
   PubMed Web of Science ®Google Scholar
• Yan X, Li H, Zhang Y, Wu S, Lu H, Yu X, Meng F, Sun J, Gong L. A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice. Acta Pharmacol Sin. 2020;41(3):348–57. doi: 10.1038/s41401-019-0295-8.
   PubMed Web of Science ®Google Scholar
• Fideles L de S, de Miranda JAL, Martins C da S, Barbosa MLL, Pimenta HB, Pimentel Pv de S, Teixeira CS, Scafuri MAS, Façanha S de O, Barreto JEF, et al. Role of rutin in 5-fluorouracil-induced intestinal mucositis: Prevention of histological damage and reduction of inflammation and oxidative stress. Molecules. 2020;25(12):2786. doi: 10.3390/molecules25122786.
   PubMed Web of Science ®Google Scholar
• Zuo T, Li X, Chang Y, Duan G, Yu L, Zheng R, Xue C, Tang Q. Dietary fucoidan of Acaudina molpadioides and its enzymatically degraded fragments could prevent intestinal mucositis induced by chemotherapy in mice. Food Funct. 2015;6(2):415–22. doi: 10.1039/C4FO00567H.
   PubMed Web of Science ®Google Scholar
• Yazbeck R, Lindsay RJ, Geier MS, Butler RN, Howarth GS. Prebiotics fructo-, galacto-, and mannan-oligosaccharide do not protect against 5-fluorouracil-induced intestinal mucositis in rats. J Nutr. 2019;149(12):2164–73. doi: 10.1093/jn/nxz192.
   PubMed Web of Science ®Google Scholar
• Galdino FMP, Andrade MER, Barros PD, Generoso S de V, Alvarez-Leite JI, Almeida-Leite CD, Peluzio M do CG, Fernandes SOA, Cardoso VN. Pretreatment and treatment with fructo-oligosaccharides attenuate intestinal mucositis induced by 5-FU in mice. J Funct Foods. 2018;49:485–92. doi: 10.1016/j.jff.2018.09.012.
   Web of Science ®Google Scholar
• Carvalho PLA, Andrade MER, Trindade LM, Leocádio PCL, Alvarez-Leite JI, dos Reis DC, Cassali GD, Souza e Melo ÉdS, dos Santos Martins F, Fernandes SOA, et al. Prophylactic and therapeutic supplementation using fructo-oligosaccharide improves the intestinal homeostasis after mucositis induced by 5-fluorouracil. Biomed Pharmacother. 2021;133:111012. doi: 10.1016/j.biopha.2020.111012.
   PubMed Web of Science ®Google Scholar
• Song M-K, Park M-Y, Sung M-K. 5-Fluorouracil-induced changes of intestinal integrity biomarkers in BALB/C mice. J Cancer Prev. 2013;18(4):322–9. doi: 10.15430/JCP.2013.18.4.322.
   PubMedGoogle Scholar
• Demedts I, Geboes K, Kindt S, Vanden Berghe P, Andrioli A, Janssens J, Tack J. Neural mechanisms of early postinflammatory dysmotility in rat small intestine. Neurogastroenterol Motil. 2006;18(12):1102–11. doi: 10.1111/j.1365-2982.2006.00857.x.
   PubMed Web of Science ®Google Scholar
• Annese V, Bassotti G, Napolitano G, Usai P, Andriulli A, Vantrappen G. Gastrointestinal motility disorders in patients with inactive Crohn’s disease. Scand J Gastroenterol. 1997;32(11):1107–17. doi: 10.3109/00365529709002989.
   PubMed Web of Science ®Google Scholar
• Akiho H, Deng Y, Blennerhassett P, Kanbayashi H, Collins SM. Mechanisms underlying the maintenance of muscle hypercontractility in a model of postinfective gut dysfunction. Gastroenterology. 2005;129(1):131–41. doi: 10.1053/j.gastro.2005.03.049.
   PubMed Web of Science ®Google Scholar
• Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4(4):277–84. doi: 10.1038/nrc1318.
   PubMed Web of Science ®Google Scholar
• Bowen JM, Gibson RJ, Cummins AG, Keefe DMK. Intestinal mucositis: The role of the Bcl-2 family, p53 and caspases in chemotherapy-induced damage. Support Care Cancer. 2006;14(7):713–31. doi: 10.1007/s00520-005-0004-7.
   PubMed Web of Science ®Google Scholar
• Ribeiro RA, Wanderley CWS, Wong DVT, Mota JMSC, Leite CAVG, Souza MHLP, Cunha FQ, Lima-Júnior RCP. Irinotecan- and 5-fluorouracil-induced intestinal mucositis: insights into pathogenesis and therapeutic perspectives. Cancer Chemother Pharmacol. 2016;78(5):881–93. doi: 10.1007/s00280-016-3139-y.
   PubMed Web of Science ®Google Scholar
• Oliveira MMB, de Araújo AA, Ribeiro SB, de Sales Mota PCM, Marques VB, da Silva Martins Rebouças C, Figueiredo JG, Barra PB, de Castro Brito GA, de Carvalho Leitão RF, et al. Losartan improves intestinal mucositis induced by 5-fluorouracil in mice. Sci Rep. 2021;11(1):23241. doi: 10.1038/s41598-021-01969-x.
   PubMed Web of Science ®Google Scholar
• Justino PFC, Melo LFM, Nogueira AF, Costa JVG, Silva LMN, Santos CM, Mendes WO, Costa MR, Franco AX, Lima AA, et al. Treatment with Saccharomyces boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in 5-fluorouracil-induced intestinal mucositis in mice. Br J Nutr. 2014;111(9):1611–21. doi: 10.1017/S0007114513004248.
   PubMed Web of Science ®Google Scholar
• Costa DVS, Bon-Frauches AC, Silva AMHP, Lima-Júnior RCP, Martins CS, Leitão RFC, Freitas GB, Castelucci P, Bolick DT, Guerrant RL, et al. 5-Fluorouracil induces enteric neuron death and glial activation during intestinal mucositis via a S100B-RAGE-NFκB-dependent pathway. Sci Rep. 2019;9(1):665. doi: 10.1038/s41598-018-36878-z.
   PubMed Web of Science ®Google Scholar
• de Miranda JAL, Martins C da S, Fideles L de S, Barbosa MLL, Barreto JEF, Pimenta HB, Freitas FOR, Pimentel Pv de S, Teixeira CS, Scafuri AG, et al. Troxerutin prevents 5-fluorouracil induced morphological changes in the intestinal mucosa: Role of cyclooxygenase-2 pathway. Pharmaceuticals 2020;13(1):10. doi: 10.3390/ph13010010.
   Web of Science ®Google Scholar
• Bowen JM, Gibson RJ, Keefe DM, Cummins AG. Cytotoxic chemotherapy upregulates pro-poptotic Bax and Bak in the small intestine of rats and humans. Pathology. 2005;37(1):56–62. doi: 10.1080/00313020400023461.
   PubMed Web of Science ®Google Scholar
• Gibson RJ, Bowen JM, Inglis MR, Cummins AG, Keefe DM. Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer. J Gastroenterol Hepatol. 2003;18(9):1095–100. doi: 10.1046/j.1440-1746.2003.03136.x.
   PubMed Web of Science ®Google Scholar
• Yeung C-Y, Chan W-T, Jiang C-B, Cheng M-L, Liu C-Y, Chang S-W, Chiang Chiau J-S, Lee H-C. Amelioration of chemotherapy-induced intestinal mucositis by orally administered probiotics in a mouse model. PLoS One. 2015;25;10(9):e0138746. doi: 10.1371/journal.pone.0138746.
   Web of Science ®Google Scholar
• Sauruk da Silva K, Carla da Silveira B, Bueno LR, Malaquias da Silva LC, da Silva Fonseca L, Fernandes ES, Maria-Ferreira D. Beneficial effects of polysaccharides on the epithelial barrier function in intestinal mucositis. Front Physiol. 2021;12:714846. doi: 10.3389/fphys.2021.714846.
   PubMed Web of Science ®Google Scholar
• Rtibi K, Selmi S, Grami D, Amri M, Sebai H, Marzouki L. Contribution of oxidative stress in acute intestinal mucositis induced by 5 fluorouracil (5-FU) and its pro-drug capecitabine in rats. Toxicol Mech Methods. 2018;28(4):262–7. doi: 10.1080/15376516.2017.1402976.
   PubMed Web of Science ®Google Scholar
• Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: An essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014;94(2):329–54. doi: 10.1152/physrev.00040.2012.
   PubMed Web of Science ®Google Scholar
• Sonis ST. The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med. 2002;13(5):380–9. doi: 10.1177/154411130201300502.
   PubMedGoogle Scholar
• Guabiraba R, Besnard AG, Menezes GB, Secher T, Jabir MS, Amaral SS, Braun H, Lima-Junior RC, Ribeiro RA, Cunha FQ, et al. IL-33 targeting attenuates intestinal mucositis and enhances effective tumor chemotherapy in mice. Mucosal Immunol. 2014;7(5):1079–93. doi: 10.1038/mi.2013.124.
   PubMed Web of Science ®Google Scholar
• Grondin JA, Kwon YH, Far PM, Haq S, Khan WI. Mucins in intestinal mucosal defense and inflammation: Learning from clinical and experimental studies. Front Immunol. 2020;11. doi: 10.3389/fimmu.2020.02054.
   Web of Science ®Google Scholar
• Williamson G, Clifford MN. Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols. Biochem Pharmacol. 2017;1;139:24-39. doi: 10.1016/j.bcp.2017.03.012.
   Web of Science ®Google Scholar
• Gençosman S, Ceylanlı D, Şehirli AÖ, Teralı K, Bölükbaşı F, Çetinel Ş, Sayıner S. Investigation of the possible protective effect of N-acetylcysteine (NAC) against irinotecan (CPT-11)-induced toxicity in rats. Antioxidants (Basel). 2022;11(11):2219. doi: 10.3390/antiox11112219.
   PubMedGoogle Scholar
• Ceylanlı D, Şehirli AÖ, Gençosman S, Teralı K, Şah H, Gülmez N, Sayıner S. Protective effects of alpha-lipoic acid against 5-fluorouracil-induced gastrointestinal mucositis in rats. Antioxidants (Basel). 2022;11(10):1930. doi: 10.3390/antiox11101930.
   PubMedGoogle Scholar