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. 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. 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.). (13)C-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.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Torres DM,Tooley KL,Butler RN,Smith CL,Geier MS,Howarth GS

doi

10.4161/cbt.7.2.5332

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

295-302

issue

2

eissn

1538-4047

issn

1555-8576

pii

5332

journal_volume

7

pub_type

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