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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) on motor coordinance. Mice were treated orally with NOSH-ASA (150 μmol/kg, v.o.), diazepam (5 mg/kg, i.p.) (positive control) or vehicle and were subjected to Rota-rod test. Sections were performed before and 1, 3, and 5 h after treatments. Data are the means ± SEM (n = 6). *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle group.
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fig03: Effect of NOSH-aspirin (NOSH-ASA) on motor coordinance. Mice were treated orally with NOSH-ASA (150 μmol/kg, v.o.), diazepam (5 mg/kg, i.p.) (positive control) or vehicle and were subjected to Rota-rod test. Sections were performed before and 1, 3, and 5 h after treatments. Data are the means ± SEM (n = 6). *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle group.

Mentions: It is important to note that sedative agents may produce false-positive effects on the acetic acid-induced writhing response test (Lopes et al. 2013). In this context, we used the rota-rod test to evaluate whether the antinociceptive effect of NOSH-aspirin upon acetic acid-induced writhing response might be due to an unspecific effect on motor coordinance. Importantly, NOSH-aspirin (150 μmol/kg, p.o.) did not change locomotor activity in all evaluated times. As a positive control, Diazepam produced significant motor impairment (Fig.3).


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) on motor coordinance. Mice were treated orally with NOSH-ASA (150 μmol/kg, v.o.), diazepam (5 mg/kg, i.p.) (positive control) or vehicle and were subjected to Rota-rod test. Sections were performed before and 1, 3, and 5 h after treatments. Data are the means ± SEM (n = 6). *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

fig03: Effect of NOSH-aspirin (NOSH-ASA) on motor coordinance. Mice were treated orally with NOSH-ASA (150 μmol/kg, v.o.), diazepam (5 mg/kg, i.p.) (positive control) or vehicle and were subjected to Rota-rod test. Sections were performed before and 1, 3, and 5 h after treatments. Data are the means ± SEM (n = 6). *P < 0.05, **P < 0.01, and ***P < 0.001 versus vehicle group.
Mentions: It is important to note that sedative agents may produce false-positive effects on the acetic acid-induced writhing response test (Lopes et al. 2013). In this context, we used the rota-rod test to evaluate whether the antinociceptive effect of NOSH-aspirin upon acetic acid-induced writhing response might be due to an unspecific effect on motor coordinance. Importantly, NOSH-aspirin (150 μmol/kg, p.o.) did not change locomotor activity in all evaluated times. As a positive control, Diazepam produced significant motor impairment (Fig.3).

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