Docosahexaenoic acid, an omega-3 polyunsaturated acid protects against indomethacin-induced gastric injury

Previous studies have shown gastroprotective effect of fish oil in several experimental models. However, the mechanisms and active compounds underlying this effect are not fully understood. Fish oil has several components; among them, one of the most studied is docosahexaenoic acid (DHA), which is an omega-3 long-chain polyunsaturated fatty acid. The aim of this study was to examine the gastroprotective effect of DHA as a pure compound in a rat model of indomethacin-induced gastric injury as well as elucidate some of the mechanism(s) behind DHA's gastroprotective effect. Indomethacin was orally administered to induce an acute gastric injury (3, 10 and 30 mg/kg). Omeprazol (a proton pump inhibitor, 30 mg/kg, p.o.) and DHA (3, 10, 30 mg/kg, p.o.) were gavaged 30 and 120 min, respectively, before indomethacin insult (30 mg/kg p.o.). Three hours after indomethacin administration, rats were sacrificed, gastric injury was evaluated by determining the total damaged area. A sample of gastric tissue was harvested and processed to quantify prostaglandin E ₂ (PGE₂) and leukotriene B₄ (LTB₄) levels by enzyme-linked immunosorbent assay. Indomethacin produced gastric injury in dose-dependent manner. DHA protected against indomethacin-induced gastric damage, and this effect was comparable with omeprazol's gastroprotective effect. DHA did not reverse the indomethacin-induced reduction of PGE ₂ gastric levels. In contrast, DHA partially prevented the indomethacin-induced increase in LTB₄ gastric levels. This is the first report demonstrating DHA's gastroprotective effect as a pure compound. Furthermore, the results reveal that the gastroprotective effect is mediated by a decrease in gastric LTB₄ levels in indomethacin-induced gastric damage.