The flavonoid luteolin inhibits cellular damage against oxidative stress via the induction of antioxidant defense system

Abstract

The present stuty was to investigate the cytoprotective effects of luteolin against the oxidative stress induced by hydrogen peroxide (H₂O₂). We found that luteolin scvanged superoxide and hydroxyl radicals generated by xanthine/xanthine oxidase and Fenton reaction (FeSO₄/H₂O₂), respectively, in a cell-free chemical system. In addition, a marked increase in cellular reactive oxygen species (ROS) was observed in H₂O₂-induced Chinese hamster lung fibroblasts (V79-4) cells. Luteolin significantly decreased the level of H₂O₂-induced intracellular ROS and damage to cellular components such as the lipid, DNA. Luteolin enhanced cell viability that decreased after H₂O₂ treatment and reduced H₂O₂-induced apoptosis via inhibition of mitochondria mediated caspases pathway. Luteolin reduced the levels of the active forms of caspase 9 and 3, reduced the expression of Bax and elevated the expression of bcl-2. Furthermore, luteolin restored the level of reduced glutathione (GSH) by H₂O₂ treatment and protein expression of a catalytically active subunit of glutamate-cysteine ligase (GCL), which is a rate-limiting enzyme in GSH biosynthesis. In addition to, luteolin increased the activities and the protein expression of cellular antioxidant enzymes like, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and hemeoxygenase-1 (HO-1). Our data suggested that luteolin prevents the cellular damage against hydrogen peroxide by inhibition of ROS and induction of antioxidant enzymes.