Anti-inflammatory and antihyperalgesic effects of the combination of ibuprofen and hemin in adjuvant-induced arthritis in the Wistar rat

Abstract

Although, pharmacological activation of heme oxygenase (HO)-1 has shown to produce ameliorative effects in various experimental models of inflammation, but such beneficial effects have not been observed in adjuvant-induced arthritis. Further, the upregulated activity of HO-1 has been implicated in the pathogenesis of adjuvant arthritis. The present study was designed to investigate the anti-inflammatory and antihyperalgesic effects of the prophylactic use of hemin alone and/or in combination with ibuprofen using adjuvant-induced arthritis in Wistar rat. Arthritis was induced by an intradermal injection of complete Freund's adjuvant (CFA) into left hind paw. Paw volume, thermal hyperalgesia, mechanical allodynia, joint stiffness and mobility behaviors (score) were measured. Administration of ibuprofen (8.75, 17.5, 35mg/kg/day, p.o.) and hemin (1, 5, 10mg/kg/day, i.p.) were significantly effective in suppressing CFA-induced paw oedema, thermal and mechanical hyperalgesia, joint stiffness and mobility. The combination of low doses of ibuprofen (8.75mg/kg, p.o.) and hemin (1mg/kg, i.p.) significantly reduced paw volume, thermal and mechanical hyperalgesia, as compared to the individual dose of the ibuprofen and hemin alone. Hence, it may be concluded that the prophylactic administration of either hemin produced significantly enhanced anti-inflammatory and analgesic effects. Further, concurrent low dose administration of hemin and ibuprofen produced significantly enhanced anti-inflammatory and analgesic effects, as compared to the either treatment alone, in CFA-induced arthritis in Wistar rats.