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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

NOSH-aspirin (NBS-1120), a dual nitric oxide and hydrogen sulfide-releasing hybrid, reduces inflammatory pain

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Author(s):
Fonseca, Miriam D. [1] ; Cunha, Fernando Q. [1] ; Kashfi, Khosrow [2, 3] ; Cunha, Thiago M. [1]
Total Authors: 4
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: PHARMACOLOGY RESEARCH & PERSPECTIVES; v. 3, n. 3 JUN 2015.
Web of Science Citations: 12
Abstract

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)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
Grantee:Fernando de Queiroz Cunha
Support Opportunities: Research Projects - Thematic Grants