Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory drug-induced mucosal damage in the murine small intestine

Abstract

Aim: To investigate the effect of a fat rich diet on non-steroidal anti-inflammatory drug (NSAID)-induced mucosal damage in the murine small intestine.

Methods: C57BL6 mice were fed 4 types of diets with or without indomethacin. One group was fed standard laboratory chow. The other groups were fed a fat diet consisting of 8% w/w fat, beef tallow (rich in SFA), fish oil, (rich in omega-3 PUFA), or safflower oil (rich in omega-6 PUFA). Indomethacin (3 mg/kg) was injected intraperitoneally from day 8 to day 10. On day 11, intestines and adhesions to submucosal microvessels were examined.

Results: In the indomethacin-treated groups, mucosal damage was exacerbated by diets containing beef tallow and fish oil, and was accompanied by leukocyte infiltration (P < 0.05). The mucosal damage induced by indomethacin was significantly lower in mice fed the safflower oil diet than in mice fed the beef tallow or fish oil diet (P < 0.05). Indomethacin increased monocyte and platelet migration to the intestinal mucosa, whereas safflower oil significantly decreased monocyte and platelet recruitment (P < 0.05).

Conclusion: A diet rich in SFA and omega-3 PUFA exacerbated NSAID-induced small intestinal damage via increased leukocyte infiltration. Importantly, a diet rich in omega-6-PUFA did not aggravate inflammation as monocyte migration was blocked.

Keywords: Adhesion molecules; Dietary fat; Non-steroidal anti-inflammatory drugs; Small intestine; Ulcer.

Figure 1

Histological evaluation of impact of indomethacin and fat-rich diets. Representative microscopic images of the small intestine are shown. Control diet (R) without indomethacin (IND) (A), with IND (B), SFA-rich diet (BT) without IND (C), with IND (D), omega-3 PUFA-rich diet (FO) without IND (E), with IND (F), and omega-6 PUFA-rich diet without IND (G), with IND (H).

Figure 2

Effect of dietary fat treatment on the recruitment of monocytes to submucosal venules. A: Change over time of monocyte adhesion in the submucosal venules of the small intestine; B: Representative photographs of in vivo monocyte adherence to small intestinal microvessels of IND and control diet (R)-treated animals; C: Representative photographs of in vivo monocyte adherence to small intestinal microvessels of IND and omega-6 PUFA diet (SO)-treated animals (n = 8 in each group). Values are represented as mean ± SEM, n = 8; ^aP < 0.05 vs IND + control diet (R); ^cP < 0.05 vs IND + omega-6 PUFA diet (SO).

Figure 3

Effect of dietary fat treatment on the recruitment of monocytes to postcapillary venules. A: Change over time of monocyte adhesion in the postcapillary venules of the small intestine; B: Representative photographs of in vivo monocyte adherence to small intestinal microvessels of IND + control diet (R)-treated animals; C: Representative photographs of in vivo monocyte adherence to small intestinal microvessels of IND + omega-6 PUFA diet (SO)-treated animals (n = 8 in each group). Values are represented as mean ± SEM, n = 8; ^aP < 0.05 vs control diet (R), ^cP < 0.05 vs IND + control diet (R), ^eP < 0.05 IND + omega-6 PUFA diet (SO).

Figure 4

Effect of dietary fat treatment on recruitment of platelets to submucosal venules. Time-course change in platelet adhesion in the submucosal venules of the small intestine. ^aP < 0.05 vs control diet (R), ^cP < 0.05 vs IND + control diet (R), ^eP < 0.05 vs IND + omega-6 PUFA diet (SO).