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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

Effect of NOSH-aspirin (NOSH-ASA) and aspirin on carrageenan- and CFA-induced inflammatory hyperalgesia. Mice were pretreated with (A) aspirin (5, 50 and 150 μmol/kg), (B) NOSH-ASA (5, 50, and 150 μmol/kg) or vehicle (v) orally (p.o.) 30 min before the intraplantar injection of carrageenan (Cg; 100 μg/paw). The hypernociceptive responses were evaluated 3 h after carrageenan injection. (C) Percentage of inhibition caused by aspirin and NOSH-ASA (150 μmol/kg) upon carrageenan-induced hyperalgesia. (D) Animals received an injection of 10 μL of CFA in the hind paw. At 24 h after, mechanical nociceptive threshold was evaluated followed by the treated with NOSH-ASA (150 μmol/kg), aspirin (150 μmol/kg) or vehicle (p.o.). Mechanical hyperalgesia was evaluated 1, 3, 5, 7, and 24 h after treatment. Data are the means ± SEM (n = 6). *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle-treated group. CFA, complete Freund’s adjuvant.
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fig04: Effect of NOSH-aspirin (NOSH-ASA) and aspirin on carrageenan- and CFA-induced inflammatory hyperalgesia. Mice were pretreated with (A) aspirin (5, 50 and 150 μmol/kg), (B) NOSH-ASA (5, 50, and 150 μmol/kg) or vehicle (v) orally (p.o.) 30 min before the intraplantar injection of carrageenan (Cg; 100 μg/paw). The hypernociceptive responses were evaluated 3 h after carrageenan injection. (C) Percentage of inhibition caused by aspirin and NOSH-ASA (150 μmol/kg) upon carrageenan-induced hyperalgesia. (D) Animals received an injection of 10 μL of CFA in the hind paw. At 24 h after, mechanical nociceptive threshold was evaluated followed by the treated with NOSH-ASA (150 μmol/kg), aspirin (150 μmol/kg) or vehicle (p.o.). Mechanical hyperalgesia was evaluated 1, 3, 5, 7, and 24 h after treatment. Data are the means ± SEM (n = 6). *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle-treated group. CFA, complete Freund’s adjuvant.

Mentions: Further investigating the potential antinociceptive effect of NOSH-aspirin, we next evaluated its effect against Cg-induced acute inflammatory hyperalgesia (Joris et al. 1987). Aspirin and NOSH-aspirin treatments were also able to inhibit Cg-induced inflammatory hyperalgesia (Fig.4A and B). Similar to that observed in the acetic acid model, whereas the intermediary dose of NOSH-aspirin (50 μmol/kg) produced a significant effect, only the higher dose of aspirin was able to reduce inflammatory hyperalgesia (Fig.4C). In terms of efficacy, at 50 μmol/kg, hyperalgesic inhibition due to aspirin was ∼25%; whereas at the same dose, NOSH-aspirin caused a 50% inhibition (Fig.4C). At the highest dose tested (150 μmol/kg), inhibition due to aspirin was ∼52%, while in the NOSH-aspirin-treated animals this effect reached ∼72% (Fig.4C).


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)

Effect of NOSH-aspirin (NOSH-ASA) and aspirin on carrageenan- and CFA-induced inflammatory hyperalgesia. Mice were pretreated with (A) aspirin (5, 50 and 150 μmol/kg), (B) NOSH-ASA (5, 50, and 150 μmol/kg) or vehicle (v) orally (p.o.) 30 min before the intraplantar injection of carrageenan (Cg; 100 μg/paw). The hypernociceptive responses were evaluated 3 h after carrageenan injection. (C) Percentage of inhibition caused by aspirin and NOSH-ASA (150 μmol/kg) upon carrageenan-induced hyperalgesia. (D) Animals received an injection of 10 μL of CFA in the hind paw. At 24 h after, mechanical nociceptive threshold was evaluated followed by the treated with NOSH-ASA (150 μmol/kg), aspirin (150 μmol/kg) or vehicle (p.o.). Mechanical hyperalgesia was evaluated 1, 3, 5, 7, and 24 h after treatment. Data are the means ± SEM (n = 6). *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle-treated group. CFA, complete Freund’s adjuvant.
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Related In: Results  -  Collection

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fig04: Effect of NOSH-aspirin (NOSH-ASA) and aspirin on carrageenan- and CFA-induced inflammatory hyperalgesia. Mice were pretreated with (A) aspirin (5, 50 and 150 μmol/kg), (B) NOSH-ASA (5, 50, and 150 μmol/kg) or vehicle (v) orally (p.o.) 30 min before the intraplantar injection of carrageenan (Cg; 100 μg/paw). The hypernociceptive responses were evaluated 3 h after carrageenan injection. (C) Percentage of inhibition caused by aspirin and NOSH-ASA (150 μmol/kg) upon carrageenan-induced hyperalgesia. (D) Animals received an injection of 10 μL of CFA in the hind paw. At 24 h after, mechanical nociceptive threshold was evaluated followed by the treated with NOSH-ASA (150 μmol/kg), aspirin (150 μmol/kg) or vehicle (p.o.). Mechanical hyperalgesia was evaluated 1, 3, 5, 7, and 24 h after treatment. Data are the means ± SEM (n = 6). *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle-treated group. CFA, complete Freund’s adjuvant.
Mentions: Further investigating the potential antinociceptive effect of NOSH-aspirin, we next evaluated its effect against Cg-induced acute inflammatory hyperalgesia (Joris et al. 1987). Aspirin and NOSH-aspirin treatments were also able to inhibit Cg-induced inflammatory hyperalgesia (Fig.4A and B). Similar to that observed in the acetic acid model, whereas the intermediary dose of NOSH-aspirin (50 μmol/kg) produced a significant effect, only the higher dose of aspirin was able to reduce inflammatory hyperalgesia (Fig.4C). In terms of efficacy, at 50 μmol/kg, hyperalgesic inhibition due to aspirin was ∼25%; whereas at the same dose, NOSH-aspirin caused a 50% inhibition (Fig.4C). At the highest dose tested (150 μmol/kg), inhibition due to aspirin was ∼52%, while in the NOSH-aspirin-treated animals this effect reached ∼72% (Fig.4C).

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