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

Fonseca MD, Cunha FQ, Kashfi K, Cunha TM - Pharmacol Res Perspect (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo Av. Bandeirantes 3900, 14049-900, Ribeirao Preto, SP, Brazil.

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 μmol/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-1β) during Cg-induced paw inflammation. Furthermore, NOSH-aspirin, but not aspirin, reduced prostaglandin E2-induced hyperalgesia, which was prevented by treatment with a ATP-sensitive potassium channel (KATP) 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 β 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.

No MeSH data available.


Related in: MedlinePlus

Structural components of NOSH-aspirin. The parent compound aspirin is shown in the shaded box. The parts of the molecule that releases NO and H2S are shown in the dotted ellipses. NO, nitric oxide; H2S, hydrogen sulfide.
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fig01: Structural components of NOSH-aspirin. The parent compound aspirin is shown in the shaded box. The parts of the molecule that releases NO and H2S are shown in the dotted ellipses. NO, nitric oxide; H2S, hydrogen sulfide.

Mentions: The following drugs and chemicals were obtained from the sources indicated: PGE2, glib., complete Freund’s adjuvant (CFA), aspirin and diazepam were from Sigma-Aldrich (St. Louis, MO); Cg (FMC Corp., Philadelphia, PA); acetic acid, dimethylsulfoxide (DMSO) and Tween 20 were from Merck (Darmstadt, Germany); NOSH-aspirin (Fig.1) [4-(3-thioxo-3H-1,2-dithiol-5-yl)phenyl 2-((4-(nitrooxy)butanoyl) oxy)benzoate] was synthesized and characterized as previously described (Kodela et al. 2012) and was a gift from Avicenna Pharmaceuticals (New York, NY). The drugs were prepared as follows: glib. was dissolved in 1% Tween 20 in saline; PGE2 was dissolved in 2% ethanol in saline; diazepam was dissolved in saline; aspirin and NOSH-aspirin were dissolved in DMSO/Tween 20 and resuspended in saline. The final concentrations of DMSO and Tween 20 were 5%.


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

Fonseca MD, Cunha FQ, Kashfi K, Cunha TM - Pharmacol Res Perspect (2015)

Structural components of NOSH-aspirin. The parent compound aspirin is shown in the shaded box. The parts of the molecule that releases NO and H2S are shown in the dotted ellipses. NO, nitric oxide; H2S, hydrogen sulfide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492749&req=5

fig01: Structural components of NOSH-aspirin. The parent compound aspirin is shown in the shaded box. The parts of the molecule that releases NO and H2S are shown in the dotted ellipses. NO, nitric oxide; H2S, hydrogen sulfide.
Mentions: The following drugs and chemicals were obtained from the sources indicated: PGE2, glib., complete Freund’s adjuvant (CFA), aspirin and diazepam were from Sigma-Aldrich (St. Louis, MO); Cg (FMC Corp., Philadelphia, PA); acetic acid, dimethylsulfoxide (DMSO) and Tween 20 were from Merck (Darmstadt, Germany); NOSH-aspirin (Fig.1) [4-(3-thioxo-3H-1,2-dithiol-5-yl)phenyl 2-((4-(nitrooxy)butanoyl) oxy)benzoate] was synthesized and characterized as previously described (Kodela et al. 2012) and was a gift from Avicenna Pharmaceuticals (New York, NY). The drugs were prepared as follows: glib. was dissolved in 1% Tween 20 in saline; PGE2 was dissolved in 2% ethanol in saline; diazepam was dissolved in saline; aspirin and NOSH-aspirin were dissolved in DMSO/Tween 20 and resuspended in saline. The final concentrations of DMSO and Tween 20 were 5%.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo Av. Bandeirantes 3900, 14049-900, Ribeirao Preto, SP, Brazil.

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 μmol/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-1β) during Cg-induced paw inflammation. Furthermore, NOSH-aspirin, but not aspirin, reduced prostaglandin E2-induced hyperalgesia, which was prevented by treatment with a ATP-sensitive potassium channel (KATP) 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 β 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.

No MeSH data available.


Related in: MedlinePlus