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Synergistic protective effects between docosahexaenoic acid and omeprazole on the gastrointestinal tract in the indomethacin‐induced injury model
Author(s) -
SánchezTrigueros Martha Ivonne,
MéndezCruz Fidel,
PinedaPeña Elizabeth Arlen,
RiveraEspinoza Yadira,
CastañedaHernández Gilberto,
ChávezPiña Aracely Evangelina
Publication year - 2021
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21772
Subject(s) - omeprazole , pharmacology , docosahexaenoic acid , gastrointestinal tract , analgesic , antipyretic , adverse effect , chemistry , stomach , medicine , polyunsaturated fatty acid , fatty acid , biochemistry
Abstract 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 ED 30 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 ED 30 ( 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.