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

A newly synthesized r uthenium 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.