Deepika Udayawara Rudresh1, Tehreem Maradagi1,2, Nimish Mol Stephen3, Ayyadurai Niraikulam2,4, Kamini Nambi Ramudu2,4, Ganesan Ponesakki5,6,7. 1. Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute (CFTRI), Mysuru, 570 020, India. 2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India. 3. Department of Fish Processing Technology, Dr. MGR Fisheries College and Research Institute, Tamil Nadu Dr. J. Jeyalalithaa Fisheries University, Ponneri, 601 204, India. 4. Department of Biochemistry and Biotechnology, CSIR-Central Leather Research Institute (CLRI), Adyar, Chennai, 600 020, India. 5. Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute (CFTRI), Mysuru, 570 020, India. ganesanp@cftri.res.in. 6. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India. ganesanp@cftri.res.in. 7. Department of Biochemistry and Biotechnology, CSIR-Central Leather Research Institute (CLRI), Adyar, Chennai, 600 020, India. ganesanp@cftri.res.in.
Abstract
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.
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.
Authors: Steven J Forrester; Daniel S Kikuchi; Marina S Hernandes; Qian Xu; Kathy K Griendling Journal: Circ Res Date: 2018-03-16 Impact factor: 17.367
Authors: G Sowmya Shree; K Yogendra Prasad; H S Arpitha; U R Deepika; K Nawneet Kumar; Priya Mondal; P Ganesan Journal: Mol Cell Biochem Date: 2017-05-26 Impact factor: 3.396
Authors: Theerut Luangmonkong; Su Suriguga; Henricus A M Mutsaers; Geny M M Groothuis; Peter Olinga; Miriam Boersema Journal: Rev Physiol Biochem Pharmacol Date: 2018 Impact factor: 5.545