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An N-Acetyl Cysteine Ruthenium Tricarbonyl Conjugate Enables Simultaneous Release of CO and Ablation of Reactive Oxygen Species.

Seixas JD, Chaves-Ferreira M, Montes-Grajales D, Gonçalves AM, Marques AR, Saraiva LM, Olivero-Verbel J, Romão CC, Bernardes GJ - Chemistry (2015)

Bottom Line: This NAC carbon monoxide releasing molecule (CORM) conjugate is able to simultaneously release biologically active CO and to ablate the concurrent formation of reactive oxygen species (ROS).Complexes of the general formulae [Ru(CO)3 (L)3 ](2+) , including [Ru(CO)3 Cl(glycinate)] (CORM-3), have been shown to produce ROS through a water-gas shift reaction, which contributes significantly, for example, to their antibacterial activity.This work highlights the advantages of combining a CO-releasing scaffold with the anti-oxidant and anti-inflammatory drug NAC in a unique pro-drug.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa (Portugal) www.gbernardes-lab.com.

No MeSH data available.


Related in: MedlinePlus

A) Effect of CORM-3, NAC-CORM and NAC at 100 μm on the inhibition of NO production (% control) in LPS-induced RAW264.7 cells. B) Effect of NAC-CORM, CORM-3 and NAC at 150 μm on the expression levels of TNF-α in the supernatant of the adenocarcinoma cell line Caco-2, measured by ELISA. Cytokine expression was measured 4 and 12 h following treatment with 150 μm of NAC-CORM, CORM-3 or NAC. Statistically significant differences found after two-way ANOVA post-hoc test using Bonferroni method are marked as * (P<0.05).
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fig04: A) Effect of CORM-3, NAC-CORM and NAC at 100 μm on the inhibition of NO production (% control) in LPS-induced RAW264.7 cells. B) Effect of NAC-CORM, CORM-3 and NAC at 150 μm on the expression levels of TNF-α in the supernatant of the adenocarcinoma cell line Caco-2, measured by ELISA. Cytokine expression was measured 4 and 12 h following treatment with 150 μm of NAC-CORM, CORM-3 or NAC. Statistically significant differences found after two-way ANOVA post-hoc test using Bonferroni method are marked as * (P<0.05).

Mentions: CO released from CORM molecules has been extensively demonstrated to possess anti-inflammatory properties.[1] NAC-CORM was designed to not only scavenge the ROS originated during the CO releasing process, but also to enhance the anti-inflammatory properties of CORMs. First, we tested the effect of NAC-CORM and CORM-3 on the production of NO from lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Remarkably, NAC-CORM was able to reduce nitrite levels in the culture by 84 % relative to control cells (Figure 4 A). This shows an enhanced reduction of nitrite levels compared to CORM-3 (58 %) and NAC (60 %) alone. In addition, we also tested the effect of NAC-CORM in the expression levels of tumour necrosis factor (TNF)-α, a key marker of inflammation progression. Both CO and NAC have been reported to influence the expression levels of TNF-α.[2, 23] Treatment of the adenocarcinoma cell line Caco-2 with NAC-CORM showed a synergistic effect promoting a substantial inhibition of the expression of endogenous TNF-α at 4 and 12 h when compared with both CORM-3 and NAC alone at the same concentration (150 μm), as measured by enzyme-linked immunosorbent assay (ELISA) (Figure 4 B). This data provides strong evidence for the synergistic effect of both CO and NAC delivered by the NAC-CORM conjugate here reported.


An N-Acetyl Cysteine Ruthenium Tricarbonyl Conjugate Enables Simultaneous Release of CO and Ablation of Reactive Oxygen Species.

Seixas JD, Chaves-Ferreira M, Montes-Grajales D, Gonçalves AM, Marques AR, Saraiva LM, Olivero-Verbel J, Romão CC, Bernardes GJ - Chemistry (2015)

A) Effect of CORM-3, NAC-CORM and NAC at 100 μm on the inhibition of NO production (% control) in LPS-induced RAW264.7 cells. B) Effect of NAC-CORM, CORM-3 and NAC at 150 μm on the expression levels of TNF-α in the supernatant of the adenocarcinoma cell line Caco-2, measured by ELISA. Cytokine expression was measured 4 and 12 h following treatment with 150 μm of NAC-CORM, CORM-3 or NAC. Statistically significant differences found after two-way ANOVA post-hoc test using Bonferroni method are marked as * (P<0.05).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4641457&req=5

fig04: A) Effect of CORM-3, NAC-CORM and NAC at 100 μm on the inhibition of NO production (% control) in LPS-induced RAW264.7 cells. B) Effect of NAC-CORM, CORM-3 and NAC at 150 μm on the expression levels of TNF-α in the supernatant of the adenocarcinoma cell line Caco-2, measured by ELISA. Cytokine expression was measured 4 and 12 h following treatment with 150 μm of NAC-CORM, CORM-3 or NAC. Statistically significant differences found after two-way ANOVA post-hoc test using Bonferroni method are marked as * (P<0.05).
Mentions: CO released from CORM molecules has been extensively demonstrated to possess anti-inflammatory properties.[1] NAC-CORM was designed to not only scavenge the ROS originated during the CO releasing process, but also to enhance the anti-inflammatory properties of CORMs. First, we tested the effect of NAC-CORM and CORM-3 on the production of NO from lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Remarkably, NAC-CORM was able to reduce nitrite levels in the culture by 84 % relative to control cells (Figure 4 A). This shows an enhanced reduction of nitrite levels compared to CORM-3 (58 %) and NAC (60 %) alone. In addition, we also tested the effect of NAC-CORM in the expression levels of tumour necrosis factor (TNF)-α, a key marker of inflammation progression. Both CO and NAC have been reported to influence the expression levels of TNF-α.[2, 23] Treatment of the adenocarcinoma cell line Caco-2 with NAC-CORM showed a synergistic effect promoting a substantial inhibition of the expression of endogenous TNF-α at 4 and 12 h when compared with both CORM-3 and NAC alone at the same concentration (150 μm), as measured by enzyme-linked immunosorbent assay (ELISA) (Figure 4 B). This data provides strong evidence for the synergistic effect of both CO and NAC delivered by the NAC-CORM conjugate here reported.

Bottom Line: This NAC carbon monoxide releasing molecule (CORM) conjugate is able to simultaneously release biologically active CO and to ablate the concurrent formation of reactive oxygen species (ROS).Complexes of the general formulae [Ru(CO)3 (L)3 ](2+) , including [Ru(CO)3 Cl(glycinate)] (CORM-3), have been shown to produce ROS through a water-gas shift reaction, which contributes significantly, for example, to their antibacterial activity.This work highlights the advantages of combining a CO-releasing scaffold with the anti-oxidant and anti-inflammatory drug NAC in a unique pro-drug.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa (Portugal) www.gbernardes-lab.com.

No MeSH data available.


Related in: MedlinePlus