Restricted accessResearch articleFirst published online 2018-04
Protective Effects of Enteral Nutrition Supplemented with Crassostrea hongkongensis Polysaccharides Against 5-Fluorouracil-Induced Intestinal Mucosal Damage in Rats
Chemotherapeutics, including 5-fluorouracil (5-FU), often damage the intestinal mucosal barrier and cause intestinal mucositis (IM). Supplementation with immunoregulatory polysaccharides from Crassostrea hongkongensis has been shown to positively influence the effectiveness and toxicity of 5-FU. Therefore, we studied the effects of oyster polysaccharides on 5-FU-induced intestinal mucosal damage in rats. The C30–60% ethanol-precipitated fraction of polysaccharides promoted IEC-6 cell proliferation and exhibited a maximal effect at a 0.0195 mg/mL concentration. Moreover, treatment with C30–60% polysaccharide-based nutrition formula (OPNF) partially prevented the 5-FU-induced degenerative changes in the histology and ultrastructure of small intestinal mucosa. In addition, the endotoxin level of rats fed with 5-FU and OPNF decreased to the normal control level. Furthermore, the 5-FU-induced increase of proinflammatory cytokine interleukin (IL)-2 and the decrease of anti-inflammatory cytokine IL-10 level in the peripheral blood were significantly attenuated by OPNF administration. In conclusion, Oyster C30–60% polysaccharides can ameliorate 5-FU-induced IM by partially preventing mucosal damage, reducing inflammation, and promoting immunity.
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References
1.
SakaiH, SagaraA, MatsumotoK, et al.: Neutrophil recruitment is critical for 5-fluorouracil-induced diarrhea and the decrease in aquaporins in the colon. Pharmacol Res, 2014; 87:71–79.
2.
JustinoPFC, MeloLFM, NogueiraAF, et al.: Regulatory role of Lactobacillus acidophilus on inflammation and gastric dysmotility in intestinal mucositis induced by 5-fluorouracil in mice. Cancer Chemother Pharmacol, 2015; 75:559–567.
3.
YuanKT, YuHL, FengWD, et al.: Bifidobacterium infantis has a beneficial effect on 5-fluorouracil-induced intestinal mucositis in rats. Benef Microbes, 2015; 6:113–118.
4.
GibsonRJ, KeefeDMK, LallaRV, et al.: Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Support Care Cancer, 2013; 21:313–326.
5.
Demoor-GoldschmidtC, RaynardB: How can we integrate nutritional support in medical oncology? [in French]. Bull Cancer, 2009; 96:665–675.
6.
SenkalM, HaakerR, LinseisenJ, WolframG, HomannHH, StehleP: Preoperative oral supplementation with long-chain Omega-3 fatty acids beneficially alters phospholipid fatty acid patterns in liver, gut mucosa, and tumor tissue. JPEN J Parenter Enteral Nutr, 2005; 29:236–240.
7.
LiG, GuRM, WenX, WeiD, MingXZ, ChenHQ: The Effect of early enteral nutrition on hyperthermic intraoperative intraperitoneal chemotherapy-induced mucosal permeability following gastrectomy. JPEN J Parenter Enteral Nutr, 2012; 36:213–218.
8.
SunpaweravongS, PuttawibulP, RuangsinS, et al.: Randomized study of antiinflammatory and immune-modulatory effects of enteral immunonutrition during concurrent chemoradiotherapy for esophageal cancer. Nutr Cancer, 2014; 66:1–5.
9.
SakuraiY, KanayaS, KomoriY, UyamaI: Is postoperative early enteral nutrition with regular or disease-specific enteral formula really beneficial in patients undergoing esophagectomy?. Esophagus Tokyo, 2009; 6:149–154.
10.
VassonMP, TalvasJ, PercheO, et al.: Immunonutrition improves functional capacities in head and neck and esophageal cancer patients undergoing radiochemotherapy: A randomized clinical trial. Clin Nutr, 2014; 33:204–210.
11.
AbreuMartinMT, TarganSR: Regulation of immune responses of the intestinal mucosa. Crit Rev Immunol, 1996; 16:277–309.
12.
MazakiT, IshiiY, MuraiI: Immunoenhancing enteral and parenteral nutrition for gastrointestinal surgery a multiple-treatments meta-analysis. Ann Surg, 2015; 261:662–669.
13.
ZuoT, CaoL, LiXM, ZhangQ, XueCH, TangQJ: The squid ink polysaccharides protect tight junctions and adherens junctions from chemotherapeutic injury in the small intestinal epithelium of mice. Nutr Cancer, 2015; 67:364–371.
14.
ZuoT, CaoL, SunXH, et al.: Dietary squid ink polysaccharide could enhance SIgA secretion in chemotherapeutic mice. Food Funct, 2014; 5:3189–3196.
15.
ZuoT, CaoL, XueCH, TangQJ: Dietary squid ink polysaccharide induces goblet cells to protect small intestine from chemotherapy induced injury. Food Funct, 2015; 6:981–986.
16.
PorporattoC, BiancoID, CorreaSG: Local and systemic activity of the polysaccharide chitosan at lymphoid tissues after oral administration. J Leukocyte Biol, 2005; 78:62–69.
17.
ChineryR, GoodladRA, WrightNA: Soy polysaccharide in an enteral diet-effects on rat intestinal-cell proliferation, morphology and metabolic function. Clin Nutr, 1992; 11:277–283.
18.
CaiBN, ChenH, SunH, WanP, SunHL, PanJY: Production of immunoregulatory polysaccharides from Crassostrea hongkongensis and their positive effects as a nutrition factor in modulating the effectiveness and toxicity of 5-FU chemotherapy in mice. Food Funct, 2016; 7:390–397.
19.
CaiBN, PanJY, WanP, ChenDK, LongSJ, SunHL: Ultrasonic-assisted production of antioxidative polysaccharides from Crassostrea hongkongensis. Prep Biochem Biotechnol, 2014; 44:708–724.
20.
ZhangCL, RenHJ, LiuMM, et al.: Modulation of intestinal epithelial cell proliferation, migration, and differentiation in vitro by Astragalus polysaccharides. PLoS One, 2014; 9:e106674.
21.
YasudaM, KatoS, YamanakaN, et al.: 5-HT3 receptor antagonists ameliorate 5-fluorouracil-induced intestinal mucositis by suppression of apoptosis in murine intestinal crypt cells. Br J Pharmacol, 2013; 168:1388–1400.
22.
FratilaOC, CraciunC: Ultrastructural evidence of mucosal healing after infliximab in patients with ulcerative colitis. J Gastrointestin Liver Dis, 2010; 19:147–153.
23.
LinZL, YuWK, TanSJ, et al.: Protective effects of terminal ileostomy against bacterial translocation in a rat model of intestinal ischemia/reperfusion injury. World J Gastroenterol, 2014; 20:17905–17913.
24.
LeaphartCL, TepasJJ: The gut is a motor of organ system dysfunction. Surgery, 2007; 141:563–569.
25.
KoufosN, MichailidouD, XynosID, et al.: Modulation of peripheral immune responses by paclitaxel-ifosfamide-cisplatin chemotherapy in advanced non-small-cell lung cancer. J Cancer Res Clin, 2013; 139:1995–2003.
26.
ChenLH, LinZB, LiWD: Ganodermalucidum polysaccharides reduce methotrexate-induced small intestinal damage in mice via induction of epithelial cell proliferation and migration. Acta Pharmacol Sin, 2011; 32:1505–1512.
27.
Abou-ElezGawishSA, NosseirDA, OmarNM, SarhanNMR: Histological and ultrastructural study of 5-fluorouracil-induced small intestinal mucosal damage in rats. Asian J Cell Biol, 2013; 8:1–21.
SchonhusenU, FloeterA, JunghansP, et al.: Morphology, proliferation, and ribonucleic acid and fractional protein syntheses in the small intestinal mucosa of young goats fed soy protein-based diets with or without amino acid supplementation. J Dairy Sci, 2010; 93:4165–4179.
30.
WongM, BarqashoB, OhrmalmL, TolfvenstamT, NowakP: Microbial translocation contribute to febrile episodes in adults with chemotherapy-induced neutropenia. PLos One, 2013; 8:e68056.
31.
GongDH, JiDX, ZhangKY, et al.: Endotoxemia after high cutoff hemodialysis for treatment of patient with multiple myeloma can be prevented by using ultrapure dialysate: A case report. Hemodial Int, 2013; 17:618–623.
32.
TsujiE, HikiN, NomuraS, et al.: Simultaneous onset of acute inflammatory response, sepsis-like symptoms and intestinal mucosal injury after cancer chemotherapy. Int J Cancer, 2003; 107:301–308.
33.
VinderolaG, PerdigonG, DuarteJ, FarnworthE, MatarC. Effects of the oral administration of the exopolysaccharide produced by Lactobacillus kefiranofaciens on the gut mucosal immunity. Cytokine, 2006; 36:254–260.
34.
SultaniM, StringerAM, BowenJM, GibsonRJ: Anti-inflammatory cytokines: Important immunoregulatory factors contributing to chemotherapy-induced gastrointestinal mucositis. Chemother Res Pract, 2012; 2012:490804.
35.
ChenJ, ZhangYD, DengZS: Imbalanced shift of cytokine expression between T helper 1 and T helper 2 (Th1/Th2) in intestinal mucosa of patients with post-infectious irritable bowel syndrome. BMC Gastroenterol, 2012; 12:91.
36.
CaiBN, PanJY, WuYT, WanP, SunHL: Immune functional impacts of oyster peptide-based enteral nutrition formula (OPENF) on mice: A pilot study. Chin J Oceanol Limnol, 2013; 31:813–820.
37.
LuoQ, CuiHM, PengX, et al.: The association between cytokines and intestinal mucosal immunity among broilers fed on diets supplemented with fluorine. Biol Trace Elem Res, 2013; 152:212–218.
38.
HansenCHF, FrokiaerH, ChristensenAG, et al.: Dietary xylooligosaccharide downregulates IFN-gamma and the low-grade inflammatory cytokine IL-1 beta systemically in mice. J Nutr, 2013; 143:533–540.
39.
HainesRJ, BeardRS, EitnerRA, ChenLW, WuMH: TNF alpha/IFN gamma mediated intestinal epithelial barrier dysfunction is attenuated by microRNA-93 downregulation of PTK6 in mouse colonic epithelial cells. PLos One, 2016; 11:e0154351.
