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Mycotoxin Research

, Volume 35, Issue 1, pp 99–109 | Cite as

Fumonisin B1-induced oxidative stress triggers Nrf2-mediated antioxidant response in human hepatocellular carcinoma (HepG2) cells

  • Thilona Arumugam
  • Yashodani Pillay
  • Terisha Ghazi
  • Savania Nagiah
  • Naeem Sheik Abdul
  • Anil A. ChuturgoonEmail author
Original Article

Abstract

Fumonisin B1 (FB1), a causative agent for animal-related mycotoxicoses, has been implicated in human and animal cancer. FB1 induces oxidative stress but the related survival responses are not well established. Central to this response is the transcription factor, nuclear factor erythroid 2 p45–related factor 2 (Nrf2). The effects of FB1 on Nrf2-related survival responses in human hepatoma (HepG2) cells were investigated. HepG2 cells were treated with 200 μmol/l FB1 (IC50–24 h). Cellular redox status was assessed via the quantification of intracellular reactive oxygen species (ROS), lipid peroxidation, protein oxidation and the antioxidant glutathione (GSH). The protein expression of oxidative stress and mitochondrial stress response proteins [Nrf2, phosphorylated-Nrf2 (pNrf2), superoxide dismutase 2 (SOD2), catalase (CAT), sirtuin 3 (Sirt 3) and Lon-protease 1 (Lon-P1)] were quantified by western blotting, while gene expression levels of SOD2, CAT and GPx were assessed using quantitative polymerase chain reaction (qPCR). Lastly, the fluorometric, JC-1 assay was used to determine mitochondrial polarisation. FB1 significantly increased ROS (p ≤ 0.001), and induced lipid peroxidation (p < 0.05) and protein carbonylation (p ≤ 0.001), which corresponded with the increase in GSH levels (p < 0.05). A significant increase in pNrf2, SOD2, SOD2, CAT (p < 0.05), CAT (p ≤ 0.01) and GPx (p ≤ 0.001) expression was observed; however, total Nrf2 (p > 0.05) was reduced. There was also a minor reduction in the mitochondrial membrane potential of HepG2 cells (p < 0.05); however, the expression of Sirt 3 and Lon-P1 (p ≤ 0.001) were upregulated. Exposure to FB1 induced oxidative stress in HepG2 cells and initiated Nrf2-regulated transcription of antioxidants.

Keywords

Fumonisin B1 Oxidative stress Reactive oxygen species Antioxidants Nuclear factor erythroid 2–related factor 2 

Notes

Acknowledgments

We thank Dr. D Moodley and Dr. A Phulukdaree for their assistance.

Funding information

TA received financial support from the National Research Foundation (NRF) of South Africa and CHS (UKZN).

Compliance with ethical standards

Conflict of interest

None.

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Copyright information

© Society for Mycotoxin Research and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical SciencesUniversity of KwaZulu-NatalDurbanSouth Africa
  2. 2.Discipline of Medical Biochemistry and Chemical Pathology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, Howard CollegeUniversity of KwaZulu-NatalDurbanSouth Africa

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