Oxidative damage and stress response from ochratoxin A exposure in rats

Ochratoxin A (OTA) is a mycotoxin found in some cereal and grain products. It is a potent renal carcinogen in male rats, although its mode of carcinog enic action is not known. Oxidative stress may play a role in OTA-induced t oxicity and carcinogenicity. In this study, we measured several chemical an d biological markers that are associated with oxidative stress response to determine if this process is involved in OTA-mediated toxicity in rats. Tre atment of male rats with OTA (up to 2 mg/kg per os, 24 h exposure) did not increase the formation of biomarkers of oxidative damage such as the lipid peroxidation marker malondialdehyde in rat plasma, kidney, and liver, or th e DNA damage marker 8-oxo-7,8-dihydro-2'deoxyguanosine in kidney DNA. Howev er, OTA treatment (1 mg/kg) did result in a 22% decrease in alpha -tocopher ol plasma levels and a 5-fold increase in the expression of the oxidative s tress responsive protein haem oxygenase-1. specifically in the kidney. The selective alteration of these latter two markers indicates that OTA does ev oke oxidative stress, which may contribute at least in part to OTA renal to xicity and carcinogenicity in rats during long-term exposure. (C) 2001 Else vier Science Inc.