Estudio de la toxicidad combinada de aflatoxina B1 y ocratoxina A en modelos "in vitro" e "in vivo"

Abstract

Aflatoxin B1 (AFB1) and ochratoxin A (OTA) are two of the most prevalent mycotoxins that can be found in edible products. AFB1 has been classified as a human carcinogen; its mechanism of action, as a direct genotoxin, has been extensively studied. OTA is a potent carcinogen in rodents but the evidence in humans in not sufficient, and the genotoxic routes are not elucidated yet. According to the literature, more than one mycotoxin may occur together in the same food, human diet is varied and furthermore, the manufacturing process mixes together different raw materials, yielding totally new matrixes with a new risk profile. Due to the fact that humans and animals are exposed to a mixture of mycotoxins and the toxic effects of the possible combined associations are still unknown, the combined toxicity needs to be studied. In vitro, AFB1 was genotoxic with metabolic activation. DNA strand breaks and FPG sensitive sites were detected. However, OTA was not genotoxic under the same conditions. Co-exposure to a mixture of AFB1 and OTA reduced the genotoxicity of AFB1, in the direct strand breaks as well. In vivo, a kinetic study in rats showed that the absorption and metabolism of AFB1 molecule are extremely fast. It appears that the presence of AFB1 does not affect the kinetics of OTA because the maximum value and the kinetic profile observed were similar to those found in previous kinetic studies conducted on OTA under the same conditions. The presence of OTA decreased the acute hepatotoxicity of AFB1. The presence of OTA reduced cytotoxicity and the percentage of micronuclei induced by AFB1 in bone marrow. The comet assay made the detection of specific organ genotoxicity possible so that AFB1 significantly induced FPG sensitive sites in liver and ochratoxin A in kidney. The presence of ochratoxin A decreased DNA damage induced by aflatoxin B1 in the liver, although the co-exposure had no effect on the kidney. In general, the exposure to both toxins simultaneously resulted in a decrease of the genotoxicity of aflatoxin B1 in both in vitro and in vivo models.