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 30mg/kg). Omeprazol (a proton pump inhibitor, 30mg/kg, p.o.) and DHA (3, 10, 30mg/kg, p.o.) were gavaged 30 and 120min, respectively, before indomethacin insult (30mg/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) (PGE(2)) and leukotriene B(4) (LTB(4)) 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 LTB(4) 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 LTB(4) levels in indomethacin-induced gastric damage.
Laboratorio de Farmacología, Programa Institucional de Biomedicina Molecular, Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, México, D.F., México.
Elizabeth Arlen
EA
Pineda-Peña
Juan Miguel
JM
Jiménez-Andrade
Gilberto
G
Castañeda-Hernández
Aracely Evangelina
AE
Chávez-Piña
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019610:Cytoprotection; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D007213:Indomethacin; D007975:Leukotriene B4 / Q000378:metabolism; D009853:Omeprazole / Q000494:pharmacology; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D007975:Leukotriene B4; D004281:Docosahexaenoic Acids; D015232:Dinoprostone; D009853:Omeprazole; D007213:Indomethacin