García-Jalón, J.A. (José Antonio)

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    Sex differences in ochratoxin a toxicity in F344 rats after 7 and 21 days of daily oral administration
    (Elsevier, 2018) Pastor, L. (Laura); García-Jalón, J.A. (José Antonio); Enciso-Gadea, J. M. (José Manuel); Lopez-de-Cerain, A. (Adela); Vettorazzi, A. (Ariane); Gonzalez-Peñas, E. (Elena); Monreal, J.I. (José Ignacio)
    Ochratoxin A (OTA) is a potent renal carcinogen in male rats but not in females. The mechanisms underlying these differences are unknown. The sex-dependent response of F344 rats after a repeated OTA oral administration for 7 (0.50 mg/kg bw) or 21 days (0.21 and 0.50 mg/kg bw) was evaluated. General toxicity, sex and thyroid hormones and histopathology were studied. OTA was quantified (HPLC-FLD) in plasma, kidney and liver and the expression of kidney transporters (RT-qPCR) was studied. After 7 days, kidney histopathology showed more pronounced signs of toxicity in males than in females. After 21 days, a higher toxicity was observed but sex differences disappeared. OTA concentration in plasma and tissues was similar in both sexes. Downregulation was the general OTA-induced effect. Oats' downregulation was slow in males and Oat3 did not change in females. Oatp1 was strongly downregulated in males after 21 days. An opposite effect was observed in Bcrp after 21 days: downregulation in males and upregulation in females. Females showed a dose- and time-dependent decrease of progesterone. Despite the sex differences, the final balance in OTA toxicokinetics at renal cell level does not seem to support a higher accumulation of OTA in male kidneys.
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    Genotoxicity of aflatoxin B1 and ochratoxin A after simultaneous application of the in vivo micronucleus and comet assay
    (Elsevier, 2014) Corcuera, L.A. (Laura Ana); García-Jalón, J.A. (José Antonio); Arbillaga, L. (Leire); Perez-Hernandez, N. (Noemí); Lopez-de-Cerain, A. (Adela); Vettorazzi, A. (Ariane); Gonzalez-Peñas, E. (Elena); Gil, A.G. (Ana Gloria); Azqueta, A. (Amaya)
    Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) are genotoxic mycotoxins that can contaminate a variety of foodstuffs, the liver and the kidney being their target organ, respectively. The micronucleus (MN) assay (bone marrow) and the comet assay (liver and kidney) were performed simultaneously in F344 rats, treated with AFB1 (0.25 mg/kg b.w.), OTA (0.5 mg/kg b.w.) or both mycotoxins. After AFB1 treatment, histopathology and biochemistry analysis showed liver necrosis, focal inflammation and an increase in Alanine Aminotransferase and Aspartate Aminotransferase. OTA alone did not cause any alteration. The acute hepatotoxic effects caused by AFB1 were less pronounced in animals treated with both mycotoxins. With regard to the MN assay, after 24h, positive results were obtained for AFB1 and negative results were obtained for OTA, although both toxins caused bone marrow toxicity. In the combined treatment, OTA reduced the toxicity and the number of MN produced by AFB1. In the comet assay, after 3h, positive results were obtained for AFB1 in the liver and for OTA in the kidney. The combined treatment reduced DNA damage in the liver and had no influence in the kidney. Altogether, these results may be indicative of an antagonistic relationship regarding the genotoxicity of both mycotoxins.