1. Synergistic interaction between docosahexaenoic acid and diclofenac on inflammation, nociception, and gastric security models in rats.
- Author
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Miranda-Lara CA, Ortiz MI, Rodríguez-Ramos F, and Chávez-Piña AE
- Subjects
- Analgesics adverse effects, Analgesics therapeutic use, Animals, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Diclofenac adverse effects, Diclofenac therapeutic use, Docosahexaenoic Acids adverse effects, Docosahexaenoic Acids therapeutic use, Dose-Response Relationship, Drug, Drug Synergism, Drug Therapy, Combination, Female, Humans, Inflammation drug therapy, Rats, Wistar, Stomach pathology, Analgesics pharmacology, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Diclofenac pharmacology, Docosahexaenoic Acids pharmacology, Nociception drug effects, Stomach drug effects
- Abstract
Preclinical Research & Development The addition of polyunsaturated fatty acids to nonsteroidal anti-inflammatory drugs can increase their antinociceptive activity and produce a gastroprotective effect. The aim of the present study was to examine the effects of the interaction between docosahexaenoic acid (DHA) and diclofenac on inflammation (fixed ratios 1:1, 1:3, and 3:1), nociception (fixed ratio 1:3), and gastric injury in rats. DHA, diclofenac, or combinations of DHA and diclofenac produced anti-inflammatory and antinociceptive effects in rat. The administration of diclofenac produced significant gastric damage, but this effect was not observed with either DHA or the DHA-diclofenac combinations. Effective dose (ED
30 ) values were estimated for each individual drug and analyzed isobolographically. The anti-inflammatory experimental ED30 values were 6.97 mg/kg (1:1 fixed ratio), 1.1 mg/kg (1:3 fixed ratio), and 11.34 mg/kg (3:1 fixed ratio). These values were significantly lower (p < .05) than the theoretical ED30 values: 67.94 mg/kg (1:1), 35.37 mg/kg (1:3), and 100.51 mg/kg (3:1). The antinociceptive experimental value was 1.25 mg/kg (1:3 fixed ratio). This value was lower (p < .05) than the theoretical ED30 , which was predicted to be 15.92 mg/kg. These data indicate that the DHA-diclofenac combinations interact at the systemic level, produce minor gastric damage, and potentially have therapeutic advantages for the clinical treatment of inflammatory pain., (© 2018 Wiley Periodicals, Inc.)- Published
- 2018
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