Human Proximal Tubule Epithelial Cells (HK-2) as a Sensitive In Vitro System for Ochratoxin A Induced Oxidative Stress

• Published in: Toxins Vol. 13; no. 11; p. 787
• Main Authors: García-Pérez, Enrique, Ryu, Dojin, Kim, Hwa-Young, Kim, Hae Dun, Lee, Hyun Jung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.11.2021; MDPI
• Subjects: Agricultural commodities; Animals; Carcinogenicity; Carcinogens; Catalase; Cell Line; Cell lines; Cytotoxicity; Enzymes; Epithelial cells; Epithelium; Gene expression; Glucose 6 phosphate dehydrogenase; Glucosephosphate dehydrogenase; Glutathione; Glutathione peroxidase; Glutathione reductase; HK-2; Humans; kidney cell lines; Kidney Tubules, Proximal - metabolism; Kidney Tubules, Proximal - physiopathology; Kidneys; LLC-PK1; LLC-PK1 Cells; mRNA; Mycotoxins; Mycotoxins - adverse effects; Ochratoxin A; ochratoxin A (OTA); Ochratoxins - adverse effects; Oxidative Stress; Parameters; Peroxidase; Proteins; Reactive oxygen species; Reductases; renal carcinogen; Superoxide dismutase; Sus scrofa; Swine; Time dependence; Toxicity; HK-2; LLC-PK1; ochratoxin A (OTA); kidney cell lines; renal carcinogen; oxidative stress
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins13110787

Ochratoxin A (OTA) is a mycotoxin that is potentially carcinogenic to humans. Although its mechanism remains unclear, oxidative stress has been recognized as a plausible cause for the potent renal carcinogenicity observed in experimental animals. The effect of OTA on oxidative stress parameters in two cell lines of LLC-PK1 and HK-2 derived from the kidneys of pig and human, respectively, were investigated and compared. We found that the cytotoxicity of OTA on LLC-PK1 and HK-2 cells was dose- and time-dependent in both cell lines. Furthermore, increased intracellular reactive oxygen species (ROS) induced by OTA in both cell lines were observed in a time-dependent manner. Glutathione (GSH) was depleted by OTA at >48 h in HK-2 but not in LLC-PK1 cells. While the mRNA levels of glucose-6-phosphate dehydrogenase (G6PD) and glutathione peroxidase 1 (GPX1) in LLC-PK1 were down-regulated by 0.67- and 0.66-fold, respectively, those of catalase (CAT), glutathione reductase (GSR), and superoxide dismutase 1 (SOD) in HK-2 were up-regulated by 2.20-, 2.24-, and 2.75-fold, respectively, after 72 h exposure to OTA. Based on these results, we conclude that HK-2 cells are more sensitive to OTA-mediated toxicity than LLC-PK1, and OTA can cause a significant oxidative stress in HK-2 as indicated by changes in the parameter evaluated.