Ferulic acid protects renal tubular epithelial cells against anoxia/reoxygenation injury mediated by AMPKα1

Abstract

Anoxia/reoxygenation (A/R) injury causes dysfunction of rat renal tubular epithelial cells (NRK-52E), which is associated with excess reactive oxygen species (ROS) generation and eventually leads to apoptosis. Ferulic acid (FA), a phenolic acid, which is abundant in fruits and vegetables. FA possesses the properties of scavenging free radicals and cytoprotection against oxygen stress. In the study, the protective effects of FA against NRK-52E cells damage induced by A/R were explored and confirmed the role of AMP-activated protein kinaseα1 (AMPKα1). We found that after NRK-52E cells suffered A/R damage, FA pretreatment increased the cell viability and decreased LDH activity in culture medium in a concentration-dependent manner, the activities of endogenous antioxidant enzymes such as glutathione peroxidase, superoxide dismutase and catalase improved, intracellular ROS generation and malondialdehyde contents mitigated. In addition, pretreatment of 75 μM FA ameliorated mitochondrial dysfunction by A/R-injury and ultimately decreased apoptosis (25.3 ± 0.61 vs 12.1 ± 0.60), which was evidenced by preventing the release of cytochrome c from mitochondria to the cytoplasm. 75 μM FA pretreatment also significantly upregulated AMPKα1 expression (3.16 ± 0.18 folds) and phosphorylation (2.56 ± 0.13 folds). However, compound C, a specific AMPK inhibitor, significantly attenuated FA pretreatment’s effects, as mentionedabove. These results firstly clarified that FA pretreatment attenuated NRK-52E cell damage induced by A/R via upregulating AMPKα1 expression and phosphorylation.

Keywords:

• Ferulic acid
• anoxia/reoxygenation injury
• NRK-52E cell
• AMPKα1
• apoptosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data that support the findings in this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This research was supported by grants from the Natural Science Foundation of China [82160685, 81803534, 81673431, 82160073].