Immunotoxic effects of Ochratoxin A in Wistar rats after oral administration

Ochratoxin A (OTA) is a mycotoxin produced by species of the genus Aspergillus and Penicillium. Human exposure has been demonstrated worldwide and its origin seems to be the intake of contaminated foods. The kidneys are the target organ of this mycotoxin. Immunotoxic and genotoxic effects of OTA were investigated in Wistar male rats (aged 12 weeks), treated by gavage with 50, 150 or 450 microg OTA/kg body weight for 28 days, in the context of a general toxicity study, which was designed following the recommendations of OECD guideline 407. At the end of the study, the mean plasma concentration of the mycotoxin was determined, several immune function assays were performed and bone marrow smears were obtained and stained in order to analyse micronuclei in polychromatic erytrocytes. Mean plasma concentration was found to be 187, 600 and 807 microg/L, respectively. At the highest dose, a decrease in body weight gain was observed. Histopathological investigations revealed tubulonephrosis and acute tubular necrosis in the kidneys of the animals treated with OTA. The frequency and severity of the lesions increased with the dose. The response of splenocytes to sheep red blood cells was decreased in a dose-dependent manner; however, nonstatistically significant differences were obtained. The natural killer cell activity was strongly affected by OTA treatment. Cytotoxic T lymphocyte activity was lower in the animals exposed to 50 microg OTA/kg b.w. but was not modified in the groups exposed to 150 and 450 microg OTA/ kg b.w. The bacteriolytic capability of macrophages was significantly reduced in groups exposed to 50 and 450 microg OTA/ kg b.w. The number of micronuclei in bone marrow polychromatic erytrocytes did not vary significantly with respect to the control at any dose, but a false negative result can not be ruled out because the exposure doses were much lower than those recommended in OECD guideline 474.