Zinc Carnosine Inhibits Lipopolysaccharide-Induced Inflammatory Mediators by Suppressing NF-kappa b Activation in Raw 264.7 Macrophages, Independent of the MAPKs Signaling Pathway

摘要

This study aimed to investigate the role of the mitogen-activated protein kinases (MAPKs) signaling pathway in the anti-inflammatory effects of zinc carnosine (ZnC) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Cells were pretreated with ZnC (0-100 mu M) for 2 h prior to the addition of LPS (1 mu g/ml). Following 24 h of treatment, ZnC was found not to be cytotoxic to RAW 264.7 cells up to the concentration of 100 mu M. Our current findings showed that ZnC did not protect RAW 264.7 cells from LPS-induced Brespiratory burst<^>. Significant increment in intracellular glutathione (GSH) level and reduction in thiobarbituric acid reactive substances (TBARS) concentration can only be observed in cell pretreated with high doses of ZnC only (50 and 100 mu M for GSH and 100 mu M only for TBARS). On the other hand, pretreatment of cells with ZnC was able to inhibit LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 expression significantly. Furthermore, results from immunoblotting showed that ZnC was able to suppress nuclear factor-kappaB (NF-kappa B) activation, and highest suppression can be observed at 100 mu M of ZnC pretreatment. However, pretreatment of ZnC did not inhibit the early activation of MAPKs. In conclusion, pretreatment with ZnC was able to inhibit the expression of inflammatory mediators in LPS-induced RAW 264.7 cells, mainly via suppression of NF-kappa B activation, and is independent of the MAPKs signaling pathway.