γ-Oryzanol suppresses cell apoptosis by inhibiting reactive oxygen species-mediated mitochondrial signaling pathway in H2O2-stimulated L02 cells

Abstract

γ-Oryzanol, a mixture of ferulic acid esters of plant sterols and triterpene alcohols existed in rice bran oil, can ameliorate lipid metabolism and enhance antioxidant activity. In this study, we used hydrogen peroxide (H₂O₂)-induced injury in human hepatic L02 cells to investigate the mechanisms involved in the hepatoprotective activity of γ-oryzanol. The injuries produced by H₂O₂ in L02 cells include increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activities of superoxide dismutase (SOD) and catalase (CAT), loss of mitochondrial membrane potential (MMP), increased protein expressions of caspase-9 and caspase-3, and induced apoptosis. Pretreatment with γ-oryzanol enhanced the ROS scavenging activity of endogenous antioxidant enzymes and decreased lipid peroxidation in H₂O₂ treated cells. Moreover, pretreatment with γ-oryzanol inhibited H₂O₂-induced apoptosis by restoring MMP, upregulating the expression ratio of Bcl-2/Bax, and inhibiting the activation of caspase-9 and caspase-3. These findings show that γ-oryzanol can prevent H₂O₂-induced apoptosis by suppressing intracellular accumulation of ROS and impeding ROS-activated mitochondrial apoptotic pathway.

Keywords: Apoptosis; L02 cells; Mitochondrial signaling pathway; Oxidative stress; γ-Oryzanol.