Long-Term Effects of Ochratoxin A on the Glutathione Redox System and Its Regulation in Chicken

The purpose of this study was to evaluate the effect of three-weeks ochratoxin A (OTA) exposure on some lipid peroxidation parameters, reduced glutathione concentration and glutathione-peroxidase activity, as well as expression of oxidative stress response-related (KEAP1, NRF2) and glutathione system (GPX3, GPX4, GSS, GSR) genes in chickens. Three levels of exposure (106, 654 and 1126 μg/kg feed) were applied. The results showed that OTA initiated free radical formation, which was suggested by the increase in the malondialdehyde content in the liver and kidney, which was more marked in the liver, depending on the length of exposure and dose. Reduced glutathione concentration increased as an effect of the highest OTA dose in blood plasma and in liver, but not in red blood cell hemolysates and the kidney. Glutathione peroxidase activity did not change in the blood and showed increasing tendency in the liver, and significant increase in the kidney. Expression of KEAP1 gene showed up-regulation in the liver, and down-regulation in the kidney, but overexpression of NRF2 gene was found in the liver and kidney at the highest dose. However, down-regulation of Nrf2 dependent genes, GPX3, GPX4, GSS and GSR, suggested an improper antioxidant response at the protein level, thus oxidative stress occurred, even at the dose of the EU regulatory limit for poultry diets.