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Papers of the Week


Papers: 25 May 2019 - 31 May 2019


Animal Studies, Pharmacology/Drug Development


2019 Aug 05


Eur J Pharmacol


856

4-Methylbenzenecarbothioamide, a hydrogen sulfide donor, inhibits tumor necrosis factor-α and CXCL1 production and exhibits activity in models of pain and inflammation.

Authors

Melo ISF, Rodrigues FF, Costa SOAM, Braga A V, Morais M Í, Vaz JA, Neto LS, Galvão I, Modolo LV, Amaral FA, Oliveira RB, de Fátima Â, Coelho MM, Machado RR
Eur J Pharmacol. 2019 Aug 05; 856:172404.
PMID: 31132352.

Abstract

The gasotransmitter hydrogen sulfide (HS) is known to regulate many pathophysiological processes. Preclinical assays have demonstrated that HS donors exhibit anti-inflammatory and antinociceptive activities, characterized by reduction of inflammatory mediators production, leukocytes recruitment, edema and mechanical allodynia. In the present study, the effects induced by 4-methylbenzenecarbothioamide (4-MBC) in models of pain and inflammation in mice, the mechanisms mediating such effects and the HS-releasing property of this compound were evaluated. 4-MBC spontaneously released HS in vitro in the absence of organic thiols. Intraperitoneal (i.p.) administration of 4-MBC (100 or 150 mg/kg) reduced the second phase of the nociceptive response induced by formaldehyde and induced a long lasting inhibitory effect on carrageenan mechanical allodynia. 4-MBC antiallodynic effect was not affected by previous administration of naltrexone or glibenclamide. 4-MBC (50, 100 or 150 mg/kg, i.p.) induced a long lasting inhibitory effect on paw edema induced by carrageenan. The highest dose (150 mg/kg, i.p.) of 4-MBC inhibited tumor necrosis factor-α and CXCL1 production and myeloperoxidase activity induced by carrageenan. Mechanical allodynia and paw edema induced by carrageenan were not inhibited by the 4-MBC oxo analogue (p-toluamide). In summary, 4-MBC, an HS releasing thiobenzamide, exhibits antinociceptive and anti-inflammatory activities. These activities may be due to reduced cytokine and chemokine production and neutrophil recruitment. The HS releasing property is likely essential for 4-MBC activity. Our results indicate that 4-MBC may represent a useful pharmacological tool to investigate the biological roles of HS.