Synergistic protective effects between docosahexaenoic acid and omeprazole on the gastrointestinal tract in the indomethacin-induced injury model

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs due to their antipyretic, anti-inflammatory, and analgesic properties. However, NSAIDs can cause adverse reactions, mainly gastrointestinal damage. Omeprazole (OMP) exhibits gastroprotective activity, but its protection is limited at the intestinal level. For this reason, it is essential to utilize a combination of therapies that provide fewer adverse effects, such as the combined treatment of OMP and docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid with anti-inflammatory, analgesic, and gastroprotective activities. The objective of this study was to evaluate the pharmacological interaction between DHA and OMP in a murine model of indomethacin-induced gastrointestinal damage. The gastroprotective and enteroprotective effects of DHA (0.3–10 mg/kg, p.o.), OMP (1–30 mg/kg, p.o.), or the combination treatment of both compounds (3–56.23 mg/kg, p.o.) were evaluated in the indomethacin-induced gastrointestinal damage model (30 mg/kg, p.o.). Since DHA and OMP exhibited a protective effect in a dose-responsive fashion, the ED₃₀ for each individual compound was determined and a 1:1 combination of DHA and OMP was tested. Isobolographic analysis was used to determine any pharmacodynamic interactions. Since the effective experimental dose ED₃₀ (Zexp) of the combined treatment of DHA and OMP was lower than the theoretical additive dose (Zadd; p <.05) in both the stomach and small intestine their protective effects were considered synergistic. These results indicate that the synergistic protective effects from combined treatment of DHA and OMP could be ideal for mitigating damage generated by NSAIDs at the gastrointestinal level.