4-metil-benzenocarbotiamida apresenta atividades em modelos experimentais de dor e inflamação

Abstract

Hydrogen sulfide (H2S) is a low molecular weight gas that mediates several pathophysiological processes, including inflammation and pain. Preclinical assays have demonstrated that H2S donors reduce production of inflammatory mediators, recruitment of leukocytes, edema, allodynia and hyperalgesia. Thiobenzamides are H2S donors and exhibit activities in many experimental models. Thus, the present study aimed to evaluate the activities of 4-methylbenzenecarbothioamide in experimental models of inflammation, and nociceptive, inflammatory and neuropathic pain in mice, as well as their mechanisms of action. 4-methylbenzenecarbothioamide (100 or 150 mg/kg, i.p., -30 min) reduced the nociceptive responde induced by formaldehyde. The second phase of this response was inhibited by both doses, while the first phase was inhibited only by the highest dose. 4-methylbenzenecarbothioamide did not inhibit the nociceptive response induced by heat (hot plate test, 50 ºC). Mechanical allodynia induced by carrageenan (600 g, 30 l, i.pl.) was attenuated by 4methylbenzenecarbothiamide (150 mg/kg). The effect induced by 4methylbenzenecarbothiamide in this model was inhibited by previous administration of cyproheptadine (5 or 10 mg/kg, p.o.), but not by naltrexone (5 or 10 mg/kg, i.p.) or glibenclamide (20 or 40 mg/kg, p.o.). 4-methylbenzenecarbothiamide did not inhibit mechanical allodynia induced by constriction of the sciatic nerve. The motor activity, evaluated by the time mice spent on the rota-rod, was not changed by 4methylbenzenecarbothiamide. 4-methylbenzenecarbothiamide (50, 100 or 150 mg/kg) inhibited paw edema, production of tumor necrosis factor- and CXCL1 and myeloperoxidase activity induced by carrageenan. It was also shown that 4methylbenzenecarbothiamide releases H2S in vitro. In conclusion, the results of the present study demonstrate the activity of 4-methylbenzenecarbothamide in different models of inflammation and nociceptive and inflammatory pain. The results indicate that the activity of 4-methylbenzenecarbothamide involves activation of the serotoninergic pathway and reduction of cytokines production and leukocyte recruitment. The demonstration of the activity of 4-methylbenzenecarbothamide in models of pain and inflammation may stimulate further studies aiming to evaluate this molecule as a potential candidate useful in the treatment of patients with painful and inflammatory disorders.