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

Hou,Shaw‑Min; Hsia,Chih‑Hsuan; Velusamy,Marappan; Jayakumar,Thanasekaran; Hsia,Chih‑Wei; Chang,Chao‑Chien; Lin,Kuan‑Hung; Lu,Yung‑Chang

doi:10.3892/ijmm.2019.4179

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
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Affiliations: Cardiovascular Center, Cathay General Hospital, Taipei 106, Taiwan, R.O.C., Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan, R.O.C., Department of Chemistry, North Eastern Hill University, Shillong 793022, India, Institute of Biomedical Sciences and Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan, R.O.C.
Published online on: May 3, 2019 https://doi.org/10.3892/ijmm.2019.4179
Pages: 335-345

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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.

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