Limits...
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-induced neutrophil migration and local production of pronociceptive cytokines. Mice were pretreated with aspirin (150 μmol/kg), NOSH-ASA (150 μmol/kg) or vehicle orally 30 min before the intraplantar injection of carrageenan (Cg; 100 μg/paw) or saline. At 3 h after Cg injection plantar tissue were collected for measurement of (A) neutrophil migration (MPO activity assay) and the levels of (B) TNF-α, (C) KC/CXCL1, and (D) IL1-β by ELISA. Data are the means ± SEM (n = 6). ***P < 0.001 versus saline group. #P < 0.05 versus vehicle-treated group. MPO, myeloperoxidase; TNF-α, tumor necrosis factor-α; KC/CXCL1, keratinocyte-derived chemokine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4492749&req=5

fig05: Effect of NOSH-aspirin (NOSH-ASA) and aspirin on carrageenan-induced neutrophil migration and local production of pronociceptive cytokines. Mice were pretreated with aspirin (150 μmol/kg), NOSH-ASA (150 μmol/kg) or vehicle orally 30 min before the intraplantar injection of carrageenan (Cg; 100 μg/paw) or saline. At 3 h after Cg injection plantar tissue were collected for measurement of (A) neutrophil migration (MPO activity assay) and the levels of (B) TNF-α, (C) KC/CXCL1, and (D) IL1-β by ELISA. Data are the means ± SEM (n = 6). ***P < 0.001 versus saline group. #P < 0.05 versus vehicle-treated group. MPO, myeloperoxidase; TNF-α, tumor necrosis factor-α; KC/CXCL1, keratinocyte-derived chemokine.

Mentions: In order to assess the mechanisms by which NOSH-aspirin further inhibits inflammatory hyperalgesia compared to aspirin, we next compared the effects of NOSH-aspirin and aspirin on Cg-induced neutrophil migration and pronociceptive cytokines production in the plantar tissue. Pretreatment with aspirin or NOSH-aspirin did not affect Cg-induced neutrophil migration in mice (Fig.5A). Although pretreatment with aspirin or NOSH-aspirin did not change the production of TNF-α (Fig.5B) or KC/CXCL1 (Fig.5C), NOSH-aspirin but not aspirin significantly reduced the production of IL-1β (Fig.5D) when compared to the vehicle-treated group. Thus, the enhanced antinociceptive effect promoted by NOSH-aspirin when compared with aspirin may in part be due to its ability to reduce IL-1-β production.


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-induced neutrophil migration and local production of pronociceptive cytokines. Mice were pretreated with aspirin (150 μmol/kg), NOSH-ASA (150 μmol/kg) or vehicle orally 30 min before the intraplantar injection of carrageenan (Cg; 100 μg/paw) or saline. At 3 h after Cg injection plantar tissue were collected for measurement of (A) neutrophil migration (MPO activity assay) and the levels of (B) TNF-α, (C) KC/CXCL1, and (D) IL1-β by ELISA. Data are the means ± SEM (n = 6). ***P < 0.001 versus saline group. #P < 0.05 versus vehicle-treated group. MPO, myeloperoxidase; TNF-α, tumor necrosis factor-α; KC/CXCL1, keratinocyte-derived chemokine.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig05: Effect of NOSH-aspirin (NOSH-ASA) and aspirin on carrageenan-induced neutrophil migration and local production of pronociceptive cytokines. Mice were pretreated with aspirin (150 μmol/kg), NOSH-ASA (150 μmol/kg) or vehicle orally 30 min before the intraplantar injection of carrageenan (Cg; 100 μg/paw) or saline. At 3 h after Cg injection plantar tissue were collected for measurement of (A) neutrophil migration (MPO activity assay) and the levels of (B) TNF-α, (C) KC/CXCL1, and (D) IL1-β by ELISA. Data are the means ± SEM (n = 6). ***P < 0.001 versus saline group. #P < 0.05 versus vehicle-treated group. MPO, myeloperoxidase; TNF-α, tumor necrosis factor-α; KC/CXCL1, keratinocyte-derived chemokine.
Mentions: In order to assess the mechanisms by which NOSH-aspirin further inhibits inflammatory hyperalgesia compared to aspirin, we next compared the effects of NOSH-aspirin and aspirin on Cg-induced neutrophil migration and pronociceptive cytokines production in the plantar tissue. Pretreatment with aspirin or NOSH-aspirin did not affect Cg-induced neutrophil migration in mice (Fig.5A). Although pretreatment with aspirin or NOSH-aspirin did not change the production of TNF-α (Fig.5B) or KC/CXCL1 (Fig.5C), NOSH-aspirin but not aspirin significantly reduced the production of IL-1β (Fig.5D) when compared to the vehicle-treated group. Thus, the enhanced antinociceptive effect promoted by NOSH-aspirin when compared with aspirin may in part be due to its ability to reduce IL-1-β production.

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