Synergistic interaction between docosahexaenoic acid and diclofenac on inflammation, nociception, and gastric security models in rats

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 ) values were estimated for each individual drug and analyzed isobolographically. The anti-inflammatory experimental ED 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 ED 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 ED , 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.

Synergistic interaction between 4‐allyl‐1‐hydroxy‐2‐methoxybenzene (eugenol) and diclofenac: An isobolograpic analysis in Wistar rats

“…So, in our work, the interaction index for phase 1 is similar to the reported for xylopic and docosahexaenoic acid but lower than the interactions demonstrated by the other authors. Likewise, for phase 2, our index of 0.09 is 45% lower than the value reported for the smallest interaction index of 0.20 for docosahexaenoic acid by Miranda‐Lara et al, 2018. In this sense, the experimental dose reported for EUG + DFC is below those reported by other works.…”

“…Thus, the degree of improved effect (synergism) reflects the value below 1 of this index, since it represents the quantitative marker for the combination of drugs and the metric of the measured effect (Tallarida, 2002). Other combinations of DFC, with natural components, have been described, such as curcumin with an interaction index of 0.51 (De Paz‐Campos, Ortiz, Piña, Zazueta‐Beltrán, & Castañeda‐Hernández, 2014), xylopic acid of 0.27 (Woode, Ameyaw, Abotsi, & Boakye‐Gyasi, 2015), Matricaria chamomilla of 0.42 (Ortiz et al, 2017), docosahexaenoic acid of 0.20 (Miranda‐Lara, Ortiz, Rodríguez‐Ramos, & Chávez‐Piña, 2018) and α‐bisabolol of 0.39 (Ortiz, Cariño‐Cortés, Ponce‐Monter, Castañeda‐Hernández, & Chávez‐Piña, 2018). So, in our work, the interaction index for phase 1 is similar to the reported for xylopic and docosahexaenoic acid but lower than the interactions demonstrated by the other authors.…”

Diclofenac Enhances Docosahexaenoic Acid-Induced Apoptosis in Vitro in Lung Cancer Cells

“…However, despite three decades of epidemiological, clinical, and experimental studies providing strong evidence of anticancer activity, the use of NSAIDs such as diclofenac for cancer chemoprevention is not recommended due to the potential risk of gastrointestinal, renal, and cardiovascular side effects [8,41,42]. Our current findings, together with the recent reports showing that the combination of NSAIDs with ω-3 PUFAs used for anti-inflammatory synergism offer protection against gastric damage induced by COX inhibitors [43,44], provide strong evidence of the benefit that could be accrued by combining the two compounds. Besides, such combination could lead to dose reduction of both agents, which could address their potential adverse effects when used alone at higher doses.…”

Herbal Medicine for Pain Management: Efficacy and Drug Interactions

“…Docosahexaenoic acid (DHA, Figure 4), a type of O3FA, has been studied in combination with drugs such as diclofenac. Animal studies on this combination attributed synergistic interaction at a systemic level in terms of nociception, inflammation and gastric security [79]. A similar study found that DHA combined with naproxen affords supra-additive nociception and gastric safety [80].…”