The effects of oral nutritional formula enriched with arginin, omega 3 fatty acids and nucleotides on methotrexate-induced experimental intestinal mucositis

This study was planned and done to investigate the effects of immunnonutritional oral formula which was enriched with arginine, omega-3 fatty acids and nucleotides, on intestinal mucosa in an experimental intestinal mucositis rat model induced by methotrexate. This study was carried out on 32 rats divided into 4 groups, upon the approval of Marmara University Animal Ethics Committee. The first group (G1)was only given saline via gavage for 5 days; the second group (G2) was given immunnonutritional oral formula (5 mg/kg) 3 times a day for 5 days. The third group (G3) was given saline via gavage for 5 days after administration of intraperitoneal single-dose methotrexate (20 mg/kg). The fourth group (G4) was given immunnonutritional oral formula 3 times a day for 5 days, after administration of intraperitoneal single-dose methotrexate (20 mg / kg). All subjects in all groups were sacrificed at 6th day. Serum TNF- α and IL- 1β levels were measured in plasma. Jejunal tissue samples, biochemical luminol, lucigenin, glutathione, myeloperoxidase, malondialdehyde and Na⁺-K⁺ ATPase levels were measured and analyzed histologically. In this study, serum Tumor necrosis factor alfa (TNF-α) and interleukin 1 beta (IL-1β) levels were significantly higher in G3 group compared to the G1 group (p<0.001). The TNF- α and IL- 1β levels in the G4 group was statistically lower than the G3 group (p < 0.001) as well. While glutathione and Na⁺ - K⁺ ATPase levels in the jejunal tissue were lower in the G3 group compared to the G1 group (p<0.05 and p<0.01 respectively); the mean value in G4 group was determined to be higher than G3 group (p<0.05). Tissue myelopexidase and malondialdehyde levels were statistically higher in the G3 group compared to the G1 group (p<0.001 and p<0.01 respectively). Myelopexidase and malondialdehyde levels in the G4 group were statistically lower than the levels in the G3 group (p<0.001 and p<0.05 respectively). Luminol and lucigenin levels were significantly higher in the G3 group compared to the G1 group (p <0.01, p <0.001). Luminol and lucigenin levels in the G4 group were significantly lower compared to the G3 group (p<0.01). The jejunal epithelium, goblet cells and gland structures were regular and uniform in G1 and G2 groups. While severe epithelium loss and increased inflammatory cell numbers were observed in the G3 group; these problems were seen declined and an increase in mitotic activity in enterocytes and a decrease in inflammatory cell density were observed in the G4 group. Our study shown that chemotherapy had adverse effects on the small intestinal mucosa. Due to its inhibition effects on neutrophil infiltration and lipid peroxidation and positive effects on glutathione and Na+- K+ ATPase levels and histological parameters, immunnonutritional oral formula shown a protective effect on intestinal damage caused by methotrexate.