Curcumin Scavenges Peroxynitrite in RAW 264.7 Macrophages through Phenolic Hydroxyl Groups

Abstract

Background: Overproduction of free radicals is implicated in cell death and tissue injury. Peroxynitrite (PN) is a highly oxidizing and short-lived free radical that is formed by the interaction of nitric oxide (NO) with superoxide. Curcumin is a natural compound obtained from Curcuma longa and has high antioxidant and anti-inflammatory activities. Aim: We investigated the PN scavenging ability of curcumin to determine its potential as a therapeutic agent for chronic diseases caused by highly oxidative molecules. Methodology: We examined the PN scavenging ability of curcumin either by directly incubating lipopolysaccharide (LPS)+interferon (IFN)-γ-stimulated RAW 264.7 murinacrophages with PN or indirectly through incubation with a PN donor (the artificial substrate SIN-1). Student t-test and one-way ANOVA were used to determine the statistical significance of differences between the experimental and control groups.  Results: The results demonstrate that curcumin inhibits PN and the synthesis of PN from SIN-1. Curcumin also significantly improved the viability of LPS+IFN-γ-treated RAW 264.7 macrophages and inhibited NO production. In macrophages, curcumin inhibited cellular PN synthesis, as evidenced by the absence of 3-nitrotyrosine, a marker of PN-oxidized proteins.  Conclusion: Curcumin attenuates the immune responses that lead to cellular damage and cell death through suppression or scavenging of cytotoxic molecules such as NO and PN. The role of the phenolic hydroxyl of curcumin is critical in PN scavenging.