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

• Published in: Drug development research 2018-08, Vol.79 (5), p.239-246
• Main Authors: Miranda‐Lara, Christopher Allan, Ortiz, Mario I., Rodríguez‐Ramos, Fernando, Chávez‐Piña, Aracely Evangelina
• Format: Article
• Language: English
• Subjects: Analgesics - adverse effects; Analgesics - pharmacology; Analgesics - therapeutic use; Animal models; Animals; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Diclofenac; Diclofenac - adverse effects; Diclofenac - pharmacology; Diclofenac - therapeutic use; Docosahexaenoic acid; Docosahexaenoic Acids - adverse effects; Docosahexaenoic Acids - pharmacology; Docosahexaenoic Acids - therapeutic use; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Fatty acids; Female; gastric damage, synergism; Humans; Inflammation; Inflammation - drug therapy; nociception; Nociception - drug effects; Nonsteroidal anti-inflammatory drugs; Pain; Pain perception; Polyunsaturated fatty acids; Rats; Rats, Wistar; Security; Stomach - drug effects; Stomach - pathology
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.21438

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 (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