TQ-6, a Novel Ruthenium Derivative Compound, Possesses Potent Free Radical Scavenging Activity in Macrophages and Rats

Abstract

Reactive oxygen species (ROS) play major role in inducing inflammation and related diseases. Our previous studies have revealed that the ruthenium (II)-compound, [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), inhibits hydroxyl radical (OH•) formation in human platelets. TQ-6 also have protective effect against induced inflammation in macrophages and hepatic injury in mice through NF-κB signaling. However, the free radical formation inhibitory mechanism of TQ-6 in macrophages is unclear. Therefore, this study detected the antioxidative ability of TQ-6 in both a cell-free system and in LPS-induced macrophages through electron spin resonance (ESR) spectrometry. TQ-6 reduced 1,1-diphenyl-2-picrylhydrazyl (DPPH), galvinoxyl, and superoxide radicals in a cell-free system and OH• formation in macrophages. Additionally, TQ-6 activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and upregulated the antioxidant protein heme oxygenase-1 (HO-1) to elevate anti-inflammatory activity in LPS-induced macrophage cells and inhibited carrageenan-induced paw edema in a rat model. Therefore, TQ-6 may prevent oxidative stress and also act as an effective therapeutic agent for the treatment of oxidant-related diseases.