Autor(es)

Fonseca, Miriam D. ^[1] ; Cunha, Fernando Q. ^[1] ; Kashfi, Khosrow ^{[2, 3]} ; Cunha, Thiago M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] CUNY, Sch Med, Sophie Davis Sch Biomed Educ, Dept Physiol Pharmacol & Neurosci, New York, NY 10031 - USA

^[3] Avicenna Pharmaceut Inc, New York, NY 10019 - USA

• Tipo de documento: Artigo Científico
• Fonte: PHARMACOLOGY RESEARCH & PERSPECTIVES; v. 3, n. 3 JUN 2015.
• Citações Web of Science: 12

Resumo

The development of nitric oxide (NO)- and hydrogen sulfide (H2S)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) has generated more potent anti-inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H2S donors into aspirin (NOSH-aspirin) was recently developed. In the present study, the antinociceptive activity of this novel molecule was compared with aspirin in different models of inflammatory pain. It was found that NOSH-aspirin inhibits acetic acid-induced writhing response and carrageenan (Cg)-induced inflammatory hyperalgesia in a dose-dependent (5-150 mu lmol/kg, v.o.) manner, which was superior to the effect of the same doses of aspirin. NOSH-aspirin's antinociceptive effect was also greater and longer compared to aspirin upon complete Freund's adjuvant (CFA)-induced inflammatory hyperalgesia. Mechanistically, NOSH-aspirin, but not aspirin, was able to reduce the production/release of interleukin-1 beta (IL-1 beta) during Cg-induced paw inflammation. Furthermore, NOSH-aspirin, but not aspirin, reduced prostaglandin E-2-induced hyperalgesia, which was prevented by treatment with a ATP-sensitive potassium channel (K-ATP) blocker (glibenclamide; glib.). Noteworthy, the antinociceptive effect of NOSH-aspirin was not associated with motor impairment. The present results indicate that NOSH-aspirin seems to present greater potency than aspirin to reduce inflammatory pain in several models. The enhanced effects of NOSH-aspirin seems to be due to its ability to reduce the production of pronociceptive cytokines such as IL-1 beta and directly block hyperalgesia caused by a directly acting hyperalgesic mediator in a mechanism dependent on modulation of KATP channels. In conclusion, we would like to suggest that NOSH-aspirin represents a prototype of a new class of analgesic drugs with more potent effects than the traditional NSAID, aspirin. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/19670-0 - Mecanismos envolvidos na fisiopatologia da artrite reumatóide, dor e sepse
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Temático