Limits...
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: 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.In contrast, NAC-CORM conjugates do not produce ROS or possess 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).
© Copyright Policy
Related In: Results  -  Collection


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.


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

Show All Figures
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: 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.In contrast, NAC-CORM conjugates do not produce ROS or possess 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