Ruthenium complex, TQ‑5, protects against LPS‑induced macrophage inflammation and acute liver injury in mice via downregulating NF‑κB pathways

  • Authors:
    • Shaw‑Min Hou
    • Chih‑Hsuan Hsia
    • Marappan Velusamy
    • Thanasekaran Jayakumar
    • Chih‑Wei Hsia
    • Chao‑Chien Chang
    • Kuan‑Hung Lin
    • Yung‑Chang Lu
  • View Affiliations

  • Published online on: May 3, 2019     https://doi.org/10.3892/ijmm.2019.4179
  • Pages: 335-345
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

A newly synthesized ruthenium metal complex, TQ‑5, exhibited antithrombotic and antiplatelet effects in our previous study. In the present study, the anti‑inflammatory/hepatoprotective effects and mechanisms of action of TQ‑5 were investigated in lipopolysaccharide (LPS)‑induced RAW 264.7 macrophages in vitro and in acute liver injury in mice in vivo. The results demonstrated that TQ‑5 suppressed the LPS‑induced production of nitric oxide, tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β) and inducible nitric oxide synthase (iNOS), without inducing cytotoxicity or damaging the morphology of the RAW 264.7 macrophages. In addition, the role of TQ‑5 in mediating mitogen‑activated protein kinases and nuclear factor κB (NF‑κB) pathways involved in the inflammation process of LPS‑stimulated RAW264.7 cells was investigated. Although TQ‑5 did not alter the phosphorylation of extracellular signal‑related kinase, p38 or c‑Jun N‑terminal kinase in LPS‑treated cells, it suppressed the phosphorylation of Akt in a concentration‑dependent manner. TQ‑5 significantly reversed the LPS‑induced degradation of inhibitor of NF‑κBα and phosphorylation of p65. The mRNA expression levels of iNOS, TNF‑α and IL‑1β were also suppressed by TQ‑5. TQ‑5 improved LPS‑induced liver injury in mice by inhibiting the expression of TNF‑α, IL‑1β and iNOS and phosphorylation of NF‑κBp65. These findings suggest that Akt/NF‑κB signaling may be a promising target for TQ‑5 to combat LPS‑induced inflammation. Therefore, TQ‑5 may act as a potential agent for the development of anti‑inflammatory drugs to treat acute liver failure.
View Figures
View References

Related Articles

Journal Cover

July-2019
Volume 44 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Hou SM, Hsia CH, Velusamy M, Jayakumar T, Hsia CW, Chang CC, Lin KH and Lu YC: Ruthenium complex, TQ‑5, protects against LPS‑induced macrophage inflammation and acute liver injury in mice via downregulating NF‑κB pathways. Int J Mol Med 44: 335-345, 2019
APA
Hou, S., Hsia, C., Velusamy, M., Jayakumar, T., Hsia, C., Chang, C. ... Lu, Y. (2019). Ruthenium complex, TQ‑5, protects against LPS‑induced macrophage inflammation and acute liver injury in mice via downregulating NF‑κB pathways. International Journal of Molecular Medicine, 44, 335-345. https://doi.org/10.3892/ijmm.2019.4179
MLA
Hou, S., Hsia, C., Velusamy, M., Jayakumar, T., Hsia, C., Chang, C., Lin, K., Lu, Y."Ruthenium complex, TQ‑5, protects against LPS‑induced macrophage inflammation and acute liver injury in mice via downregulating NF‑κB pathways". International Journal of Molecular Medicine 44.1 (2019): 335-345.
Chicago
Hou, S., Hsia, C., Velusamy, M., Jayakumar, T., Hsia, C., Chang, C., Lin, K., Lu, Y."Ruthenium complex, TQ‑5, protects against LPS‑induced macrophage inflammation and acute liver injury in mice via downregulating NF‑κB pathways". International Journal of Molecular Medicine 44, no. 1 (2019): 335-345. https://doi.org/10.3892/ijmm.2019.4179