Lyprinol™ only partially improves indicators of small intestinal integrity in a rat model of 5-fluorouracil-induced mucositis

Abstract

Background: Intestinal mucositis is a common and debilitating side-effect of chemotherapy, associated with severe small intestinal inflammation. Marine oils, such as Lyprinol™, a lipid extract derived from New Zealand Green-lipped Mussels, rich in long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA), have demonstrated therapeutic potential for the treatment of inflammatory conditions. We assessed the effects of Lyprinol™ on the severity of 5-fluorouracil (5-FU)-induced mucositis in female Dark Agouti rats. Methods: Rats were allocated to six groups (n=8/group); Saline+vehicle, 5-FU+vehicle, 5-FU+high-dose Lyprinol™ (5-FU+HDL), 5-FU+low-dose Lyprinol™ (5-FU+LDL), 5-FU+olive oil (5-FU+OO), and 5-FU+fish oil (5-FU+FO). Treatments were administered via oro-gastric gavage from days 0-7. Mucositis was induced on day 5 by 5-FU injection (150mg/kg i.p.). 13C-sucrose breath tests (SBT) were conducted on days 0, 5 and 8 to assess small intestinal function. Rats were sacrificed on day 8 and small intestinal tissues collected for histological and biochemical analysis. Results: Small intestinal weight was significantly greater in rats treated with 5-FU+HDL, 5-FU+LDL and 5-FU+FO compared to 5-FU-treated controls (p < 0.05). Myeloperoxidase activity in the proximal and mid small intestine were significantly lower in 5-FU+OO-treated rats compared to 5-FU+vehicle-treated controls (p < 0.05). Histological damage severity was elevated in 5-FU+vehicle, 5-FU+OO and 5-FU+FO-treated rats compared to saline-treated controls, but not in rats treated with 5-FU+HDL or 5-FU+LDL. SBT results and biochemically-assessed sucrase activity were lower in all 5-FU-treated rats compared to saline-treated controls. 5-FU+HDL treated animals had significantly longer crypts and increased proliferation in the mid small intestine compared to 5-FU+vehicle rats (p < 0.05). Conclusion: Lyprinol™ treatment in rats with 5-FU-induced mucositis only minimally decreased indicators of intestinal integrity. Further studies of marine oils high in omega-3 PUFA content are warranted for the potential prophylactic treatment of intestinal mucositis.