Investigation of toxic effects of zearalenone on human kidney cells

Zearalenone (ZEA) is a mycotoxin that is widely found worldwide produced by several fungal species. Due to its similarity to estradiol, its toxic effects on the reproductive system has been shown. Although various animal studies have been conducted to elucidate the toxic effects of ZEA, the mechanisms of toxicity have not been fully elucidated. The aim of this Master Thesis is to investigate the dose dependent toxic effects of ZEA exposure in human kidney cells (HK-2). For this purpose, the effects of ZEA on cytotoxicity, cell proliferation, reactive oxygen species (ROS), DNA methylation and expression of DNMT1, MGMT, α-GST, Hsp70, Nrf2, L-Fabp and HO-1 genes in HK-2 cells were investigated. IC50 values of ZEA in HK-2 cells were found to be as 133.42 and 101.74 µM according to MTT and NRU tests, respectively. ZEA exposure at the concentrations of 1, 10 and 50 µM decreased the BrdU cell proliferation by 2.1%, 11.07% (p<0,05) and 24.34% (p<0,001), respectively. ROS levels were found to be significantly increase with 1, 10 and 50 µM concentrations of ZEA as (27.69%), 64.25% and 103.82%, respectively. Significant change was observed at the levels of global 5-methylcytosine in all exposure groups, while expression of DNMT and MGMT genes increased significantly. A significant increase was observed in the expressions of α-GST, Hsp70 and HO-1 genes which are associated with oxidative damage, while a significant decrease in L-Fabp gene was observed. No change was found in the Nrf2 gene. These results indicate that changes in DNA methylation and oxidative damage may have an important role in the toxicity of ZEA.