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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 acetic acid-induced writhing responses in mice. Animals were pretreated orally (p.o.) with aspirin (5, 15, 150 μmol/kg), NOSH-ASA (5, 15, 150, and 450 μmol/kg) or vehicle (v), 50 min before the intraperitoneal administration of acetic acid (0.8%, i.p.). Writhing responses was assessed during 20 min after acetic acid injection. The graphic represents the percentage of inhibition relative to vehicle. Data are the means ± SEM (n = 7). *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle group.
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fig02: Effect of NOSH-aspirin (NOSH-ASA) and aspirin on acetic acid-induced writhing responses in mice. Animals were pretreated orally (p.o.) with aspirin (5, 15, 150 μmol/kg), NOSH-ASA (5, 15, 150, and 450 μmol/kg) or vehicle (v), 50 min before the intraperitoneal administration of acetic acid (0.8%, i.p.). Writhing responses was assessed during 20 min after acetic acid injection. The graphic represents the percentage of inhibition relative to vehicle. Data are the means ± SEM (n = 7). *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle group.

Mentions: Intraperitoneal injection of acetic acid-induced writhing response has been extensively used in the screening of novel analgesic drugs (Collier et al. 1968). Thus, this nociceptive behavior test was initially used to evaluate the possible antinociceptive effect of NOSH-aspirin in comparison to that of aspirin. NOSH-aspirin and aspirin were both effective in inhibiting acetic acid-induced writhing response in a dose-dependent manner (Fig.2). However, whereas only the highest dose of aspirin presented a significant effect, the low and intermediary doses of NOSH-aspirin were significantly effective in inhibiting the writhing responses (Fig.2). Regarding efficacy, at the highest dose tested (450 μmol/kg), inhibition due to aspirin was ∼49%, while in the NOSH-aspirin-treated animals this effect reached ∼59% (Fig.2). Although NOSH-aspirin’s effect was higher than aspirin at this dose no statistical difference (P = 0.089) was observed.


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 acetic acid-induced writhing responses in mice. Animals were pretreated orally (p.o.) with aspirin (5, 15, 150 μmol/kg), NOSH-ASA (5, 15, 150, and 450 μmol/kg) or vehicle (v), 50 min before the intraperitoneal administration of acetic acid (0.8%, i.p.). Writhing responses was assessed during 20 min after acetic acid injection. The graphic represents the percentage of inhibition relative to vehicle. Data are the means ± SEM (n = 7). *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Effect of NOSH-aspirin (NOSH-ASA) and aspirin on acetic acid-induced writhing responses in mice. Animals were pretreated orally (p.o.) with aspirin (5, 15, 150 μmol/kg), NOSH-ASA (5, 15, 150, and 450 μmol/kg) or vehicle (v), 50 min before the intraperitoneal administration of acetic acid (0.8%, i.p.). Writhing responses was assessed during 20 min after acetic acid injection. The graphic represents the percentage of inhibition relative to vehicle. Data are the means ± SEM (n = 7). *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle group.
Mentions: Intraperitoneal injection of acetic acid-induced writhing response has been extensively used in the screening of novel analgesic drugs (Collier et al. 1968). Thus, this nociceptive behavior test was initially used to evaluate the possible antinociceptive effect of NOSH-aspirin in comparison to that of aspirin. NOSH-aspirin and aspirin were both effective in inhibiting acetic acid-induced writhing response in a dose-dependent manner (Fig.2). However, whereas only the highest dose of aspirin presented a significant effect, the low and intermediary doses of NOSH-aspirin were significantly effective in inhibiting the writhing responses (Fig.2). Regarding efficacy, at the highest dose tested (450 μmol/kg), inhibition due to aspirin was ∼49%, while in the NOSH-aspirin-treated animals this effect reached ∼59% (Fig.2). Although NOSH-aspirin’s effect was higher than aspirin at this dose no statistical difference (P = 0.089) was observed.

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