Luteolin alleviates ochratoxin A induced oxidative stress by regulating Nrf2 and HIF-1α pathways in NRK-52E rat kidney cells

Ochratoxin A (OTA) is a ubiquitous food contaminant and a critical food safety concern due to its nephron toxic effects, which impacts all parts of the world. Luteolin (LUT) had gained increasing interest as a health-promoting food antioxidant component. However, the preventative effect of LUT against OTA induced oxidative stress was not yet clear and the elucidation of which would provide critical information to develop dietary LUT as a control strategy for OTA. In the current study, the cytoprotective effect of LUT against OTA induced oxidative stress and the mechanism(s) behind was examined in NRK-52E rat kidney cells. The results showed that LUT exerted its preventative effect via restoring cell viability and preventing LDH release. It alleviated the OTA-induced oxidative stress and lipid peroxidation by reducing ROS accumulation, ameliorating the mitochondrial membrane potential reduction and reversing the activities of antioxidant enzymes to the control levels. The regulating roles of Nrf2 and HIF-1 alpha in this process were evaluated by cell immunofluorescence assay, reporter plasmids transfection assay and qRT-PCR analysis. The results showed that LUT activated Nrf2 pathway and increased the antioxidant defense capacities of OTA treated cells. Additionally, LUT also modulated HIF-1 alpha pathway to initiate the angiogenesis and epithelial restitution process.