Background: The liver has a solid inbuilt antioxidant defense system to regulate oxidative stress. However, exposure to an excessive level of ROS causes liver injury. This study examined the cytoprotective effect of neoxanthin, a xanthophyll antioxidant molecule isolated from Solanum trilobatum in stress-induced HepG2 cells.
Methods and results: The cytotoxic effect of H2O2 and cytoprotective potential of β-carotene, lutein, and neoxanthin was analyzed by WST-1 assay. The intracellular ROS level and mitochondrial membrane potential (MMP) were measured using DCFH-DA (2', 7'-dichlorofluorescin diacetate) and JC-10 MMP assay. The expression of anti-oxidant and apoptotic markers was measured by western blot analysis. Neoxanthin pretreatment exhibited better protection than β-carotene and lutein against cell death caused by H2O2. It significantly arrested H2O2-mediated elevation of intracellular ROS levels and protected MMP. The intracellular antioxidant enzymes HO-1 and SOD-2 were upregulated by neoxanthin pretreatment. Neoxanthin also activated the protein expression of redox-sensitive transactivation factors, Nrf2 and NF-kB. The cytoprotective effect of neoxanthin was associated with increased expression of the anti-apoptotic protein, Bcl-2 and decreased pro-apoptotic protein Bax.
Conclusions: For the first time, our results demonstrate that neoxanthin offers adequate protection against stress-mediated cytotoxicity in hepatocytes by activating the intracellular antioxidant defense system and blocking apoptosis.
Keywords: Antioxidant enzymes; Apoptosis; Carotenoids; Cytoprotection; HepG2 cells; Neoxanthin.
© 2021. The Author(s), under exclusive licence to Springer Nature B.V.