© 2018 Wiley Periodicals, Inc. (Table presented.). 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 (ED30) 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.
Miranda-Lara, C. A., Ortiz, M. I., Rodríguez-Ramos, F., & Chávez-Piña, A. E. (2018). Synergistic interaction between docosahexaenoic acid and diclofenac on inflammation, nociception, and gastric security models in rats. Drug Development Research, 239-246. https://doi.org/10.1002/ddr.21438