PPARγ Activation Protects against Hydrogen Peroxide-Induced Oxidative Stress and Apoptosis in Human Liver Cells

The deleterious role of oxidative stress in liver damage is a growing problem, and effective therapeutic interventions are highly warranted. This study evaluated whether peroxisome proliferator-activated receptor gamma (PPARγ) activation protects against H₂O₂-induced oxidative stress and apoptosis in human L02 hepatocytes. Cells pretreated with rosiglitazone, a PPARγ agonist, were incubated with H₂O₂, and cell viability was assessed using CCK8 and LDH release assays 24 h after the treatment. The content of apoptotic cells was determined using Hoechst 33258 staining, and the levels of apoptosis-related proteins were determined by immunoblotting. In addition, several oxidative stress indicators were measured. Possible involvement of the nuclear factor erythroid 2-related factor (Nrf2) pathway was investigated using the Nrf2 inhibitor ML385. Rosiglitazone (20 μM) increased cell viability and improved nuclear morphology in H₂O₂-treated L02 cells, possibly by increasing the Bcl-2/Bax ratio and reducing caspase-3 activation. Rosiglitazone also decreased reactive oxygen species and malonaldehyde levels, as well as increased the activities of catalase, glutathione peroxidase, and superoxide dismutase. Rosiglitazone also promoted nuclear translocation of Nrf2 and increased the antioxidant levels in H₂O₂-treated L02 cells. Inhibition of the Nrf2 pathway by ML385 partially abolished the rosiglitazone-induced amelioration of oxidative stress and apoptosis. We conclude that activation of PPARγ protects liver cells against oxidative stress and apoptosis through the Nrf2 pathway.