Acute Ochratoxin A exposure induces inflammation and apoptosis in human embryonic kidney (HEK293) cells

Ochratoxin A (OTA), a common contaminant of grain and fruit and known carcinogen, has been linked to impaired antioxidant response and cellular repair. The effect of OTA on inflammation in cells has not been explored. This study investigated OTA's influence on inflammatory mediators using a range of OTA concentrations (0.5 mu M (sub-IC50), 1.2 mu m (IC50) and 2 gm (supra-IC50)) on human embryonic kidney (HEK293) cells over 24hr. The markers of inflammation in HEK293 cells were evaluated using the following techniques: western blotting (phosphorylated (p-)NF kappa B (Ser536), p-IKK (Ser176/180) and p-p53 (Ser392), total NF kappa B, IKK, I kappa B alpha and p53), luminometry (caspases 1, 3/7, 8, 9, ATP) and ELISA to determine IL-1 beta levels. The results indicate increased activation of the inflammatory pathway in the sub-IC50 concentration, evidenced by significant increases in p-NF kappa B (p = 0.0006). The IC50 concentration indicates decreased inflammatory induction supported by decreased levels of IL-1 beta and caspase 1 (p = 0.0186 and p = 0.0068 respectively) with decreased IKK and increased I kappa B alpha (p = 0.0046 and p = 0.0006 respectively). Furthermore, a decrease in inflammatory pathway activation was seen in O3 (increased I kappa B alpha, p < 0.05) coupled with increased apoptosis via elevated caspase 3/7 (p = 0.0002), 8 (p = 0.0011) and 9 activity (p = 0.0002); as well as decreased ATP levels. This data suggests a new mechanism of OTA toxicity and its involvement in inflammation, kidney disease and fibrosis. (C) 2017 Elsevier Ltd. All rights reserved.