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 carcinogenic action is not known. Oxidative stress may play a role in OTA-induced toxicity and carcinogenicity. In this study, we measured several chemical and biological markers that are associated with oxidative stress response to determine if this process is involved in OTA-mediated toxicity in rats. Treatment of male rats with OTA (up to 2 mg/ 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 the DNA damage marker 8-oxo-7,8-dihydro-2' deoxyguanosine in kidney DNA. However, OTA treatment (1 mg/kg) did result in a 22% decrease in alpha-tocopherol plasma levels and a 5-fold increase in the expression of the oxidative stress responsive protein haem oxygenase-1, specifically in the kidney. The selective alteration of these latter two markers indicates that OTA does evoke oxidative stress, which may contribute at least in part to OTA renal toxicity and carcinogenicity in rats during long-term exposure.
Gautier
J C
JC
Nestlé Research Center, Nestec Ltd., Lausanne, Switzerland.
Holzhaeuser
D
D
Markovic
J
J
Gremaud
E
E
Schilter
B
B
Turesky
R J
RJ
D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D005290:Ferric Compounds / Q000633:toxicity; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D009183:Mycotoxins / Q000633:toxicity*; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D009793:Ochratoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000097:blood
D002273:Carcinogens; D005290:Ferric Compounds; D006360:Heat-Shock Proteins; D009183:Mycotoxins; D009793:Ochratoxins; D006151:Guanosine; D014810:Vitamin E; C025589:ochratoxin A; C046215:8-hydroxyguanosine; D008315:Malondialdehyde; D006419:Heme Oxygenase (Decyclizing); D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate