Curcumin Protects Pheochromocytoma Cells Against Hydrogen Peroxide-Induced Oxidative Stress

Objective: Oxidative stress represents a characteristic of neurodegenerative diseases, which may be alleviated by the functional food component-curcumin. However, the underlying mechanism remains unclear. The current study aimed to address how curcumin protects variant differentiated pheochromocytoma (PC12) cells against hydrogen peroxide (H2O2)-induced cell stress, using low- and high-differentiated PC12 cells, and validated in old-aged mice. Methods: The MTT assay was first carried out to test the cell viability upon H2O2 and/or curcumin treatment and cellular lipid peroxidation was assessed as cellular damages by quantifying the amount of cellular malondialdehyde. Cellular oxidative stress was determined by measuring the cellular and mitochondrial ROS levels, and total cellular antioxidant capacities were determined as the ABTS free radical scavenging ability (ABTS) and Fe3+ reduction ability of cells. The activities and expression of major antioxidant enzymes, including glutathione peroxidase (GPx), superoxidase dismutase (SOD) and catalase (CAT), were also tested. Furthermore, oxidative phosphorylation of mitochondria was assessed by measuring the ATP level and the ADP/ATP ratio. Finally, the antioxidant activity of curcumin was determined in 6-month-old mice by measuring cellular antioxidant capacity and antioxidant enzyme activities. Results: H2O2 caused oxidative damage and decreased cell viability, which was reversed by curcumin with different dosed effects in variant differentiated PC12 cells. Moreover, curcumin's protective effect was attributed to an enhanced antioxidant enzyme system. In consistent, curcumin recovered H2O2-deteriorated oxidative phosphorylation. Further studies verified that curcumin significantly improved the antioxidant capacity of old-aged mice, which may have elevated oxidative stress. Conclusion: Taken together, curcumin improved the antioxidant capacity of variant differentiated PC12 cells and old-aged mice, which was closely associated with the modulation of mitochondrial function and antioxidant enzyme system. This study may shed light on the molecular mechanism underlying the alleviation of neurodegenerative diseases by natural polyphenols.