Patulin triggers NRF2-mediated survival mechanisms in kidney cells

Toxicon : Official Journal of the International Society on Toxinology
Y PillayA A Chuturgoon

Abstract

Patulin (PAT), a mycotoxin contaminant of apples and apple products, has been implicated in nephrotoxicity. PAT depletes glutathione (GSH) and elevates reactive oxygen species (ROS). The antioxidant (AO) response is activated by Nuclear erythroid 2-related factor (NRF2) and enhanced by Silent information regulator 3 (SIRT3). The effects of PAT on these molecules have yet to be examined. We investigated the effects of PAT on AO response survival pathways in human embryonic kidney cells (HEK293). PAT cytotoxicity on HEK293 cells was evaluated (MTT assay; 24 h; [0-100 μM]) to determine an IC50. GSH levels were measured using luminometry. Intracellular ROS was evaluated by flow cytometry. Protein expression of Keap1, NRF2, SIRT3 and PGC-1α was quantified by western blotting and gene expression of SOD2, CAT and GPx was evaluated by qPCR. PAT caused a dose dependent decrease in HEK293 cell viability and a significant increase in levels of intracellular ROS (p = 0.0006). A significant increase in protein expression (p = 0.029) was observed. PAT increased gene expression of SOD2 and CAT (p = 0.0043), however, gene expression of GPx was significantly reduced (p = 0.0043). These results show the up-regulation of NRF2 mediated AO mechanis...Continue Reading

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Citations

Nov 21, 2015·Neurotoxicology·Manel BoussabbehSalwa Abid-Essefi
Oct 9, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Leila MaidanaAna Paula F R L Bracarense
Jan 31, 2021·Toxicon : Official Journal of the International Society on Toxinology·Siqiniseko NdlovuAnil A Chuturgoon
Jan 7, 2021·Mycotoxin Research·Yashodani PillayAnil A Chuturgoon
Nov 20, 2020·Scientific Reports·Yashodani PillayAnil A Chuturgoon
Feb 13, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Jiahui HanXiaoli Peng
Apr 10, 2018·Chemico-biological Interactions·Taskeen Fathima DocratAnil A Chuturgoon

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