Atividades do ácido 4-((nitrooxi) metil)-3-nitrobenzoico em modelos de dor e inflamação.

Abstract

The development of different nitric oxide (NO) donor substances has increased due to the contribution of the signaling pathway mediated by this molecule in the control of several clinical conditions, including inflammatory and painful manifestations. Structural modification for NO release may result in substances with better anti-inflammatory and antinociceptive activities and with a better safety profile. Thus, the aim of the present study was to evaluate the activities of the compound 4-((nitrooxy)methyl)-3-nitrobenzoic acid (RIY09), a NO donor, in experimental models of pain and inflammation, as well as the possible mechanisms involved. Intraperitoneal (i.p.) administration of compound RIY09 (100 or 150 mg/Kg) inhibited heat-induced nociceptive response and carrageenan-induced mechanical allodynia. The motor activity of the animals was not altered by the administration of 150 mg/Kg, i.p. of compound RIY09. Pretreatment with compound RIY09 (50, 100 and 150 mg/Kg, i.p.) also reduced carrageenan-induced paw edema. Activities in inflammatory pain and edema models were associated with decreased neutrophil recruitment and decreased production of inflammatory cytokines such as IL1β, IL-6, TNF-α and CXCL-1, and increased production of the anti-inflammatory cytokine IL- 10. The i.p. of the compound RIY09 (50, 100 and 150 mg/Kg) reduced the mechanical allodynia induced by paclitaxel on the 7th day of sensitization with the chemotherapy. Previous administration of AM251 (4 or 8 mg/Kg, i.p.) and naltrexone (10 mg/Kg, i.p.) but not glibenclamide (20 or 40 mg/Kg, p.o.), reduced the antinociceptive activity of compound RIY09. The RIY09 compound also reduced the production of inflammatory cytokines in structures such as DRGs and thalamus. After 5 h of i.p administration of compound RIY09 (150 mg/Kg) there was an increase in plasma nitrite concentrations, indicating that this compound possibly releases NO, correlating with the activities presented by this new compound. Thus, our results demonstrate that the compound RIY09 presents antinociceptive and anti-inflammatory activities in the evaluated experimental models. These results reinforce the interest in investigating NO donor compounds as candidates for analgesic and anti-inflammatory drugs.