4-Methylbenzenecarbothioamide, a hydrogen sulfide donor, inhibits tumor necrosis factor-α and CXCL1 production and exhibits activity in models of pain and inflammation
| Autor: | Renata B. Oliveira, Leonardo da Silva Neto, Márcio M. Coelho, Alysson Vinícius Braga, Ângelo de Fátima, Felipe F. Rodrigues, Marcela I. Morais, Flávio A. Amaral, Renes R. Machado, Izabela Galvão, Luzia V. Modolo, Jéssica A. Vaz, Ivo S.F. Melo, Sarah O.A.M. Costa |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Nociception Chemokine medicine.medical_treatment Chemokine CXCL1 Pain Inflammation Pharmacology Motor Activity Glibenclamide 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Edema medicine Benzene Derivatives Animals Hydrogen Sulfide skin and connective tissue diseases biology Chemistry Tumor Necrosis Factor-alpha Amides Carrageenan CXCL1 Thioamides Disease Models Animal 030104 developmental biology Cytokine Hyperalgesia biology.protein Tumor necrosis factor alpha medicine.symptom 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | European journal of pharmacology. 856 |
| ISSN: | 1879-0712 |
| Popis: | The gasotransmitter hydrogen sulfide (H2S) is known to regulate many pathophysiological processes. Preclinical assays have demonstrated that H2S 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 H2S-releasing property of this compound were evaluated. 4-MBC spontaneously released H2S 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 H2S releasing thiobenzamide, exhibits antinociceptive and anti-inflammatory activities. These activities may be due to reduced cytokine and chemokine production and neutrophil recruitment. The H2S 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 H2S. |
| Databáze: | OpenAIRE |
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