Electrochemical evidence of nitrate release from the nitrooxy compound 4-((nitrooxy) methyl)-3-nitrobenzoic acid and its antinociceptive and anti-inflammatory activities in mice
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Universidade Federal de Minas Gerais
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Considering the many biological activities of nitric oxide (NO), some lines of research focused on the modulation
of these activities through the provision of this mediator by designing and synthesizing compounds coupled with
an NO donor group. Thus, the objectives of the present study were to carry out an electrochemical investigation
of the nitrooxy compound 4-((nitrooxy) methyl)-3-nitrobenzoic acid (1) and evaluate its activities and putative
mechanisms in experimental models of pain and inflammation. Voltammetric studies performed in aprotic
medium (mimetic of membranes) showed important electrochemical reduction mechanisms: nitroaromatic
reduction, self-protonation, and finally reductive elimination, which leads to nitrate release. Systemic admin istration of the nitrooxy compound (1) inhibited the nociceptive response induced by heat and the tactile hypersensitivity and paw edema induced by carrageenan in mice. The activities in the models of inflammatory pain
and edema were associated with reduced neutrophil recruitment and production of inflammatory cytokines, such
as interleukin (IL)-1β, IL-6, tumor necrosis factor-α and CXCL-1, and increased production of IL-10. Concluding,
electrochemical analysis revealed unequivocally that electron transfer at the nitro group of the nitrooxy com pound (1) results in the cleavage of the organic nitrate, potentially resulting in the generation of NO. This
electrochemical mechanism may be compared to a biochemical electron-transfer mediated nitrate release that,
by appropriate in vivo bioreduction (enzymatic or not) would lead to NO production. Compound (1) exhibits
activities in models of inflammatory pain and edema that may be due to reduced recruitment of neutrophils and
production of inflammatory cytokines and increased production of IL-10. These results reinforce the interest in
the investigation of NO donor compounds as candidates for analgesic and anti-inflammatory drugs.
Abstract
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Farmácia, Química
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Farmácia, Química
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https://www.sciencedirect.com/science/article/pii/S0753332220311057?via%3Dihub