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Alterations induced in vitro by ochratoxin a in rat lymphoid cells

Food Sciences and Toxicology Department, Faculty of Pharmacy, University of Navarra, Irunlarrea, Pamplona, Spain

C Leache

E González-Peñas

Organic and Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Navarra, Irunlarrea, Pamplona, Spain

A López de Cerain

Food Sciences and Toxicology Department, Faculty of Pharmacy, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spainacerain{at}unav.es

Ochratoxin A (OTA) is a nephrotoxic mycotoxin produced by species of the genus Penicillium and Aspergillus that is present in food and feed as a natural contaminant. It modifies the immune function in animals and inhibits the proliferative response of lymphocytes in vitro. The toxic effect of OTA (0.5, 2, 20 mM) in lymphoproliferative response, natural killer (NK) cell activity, cytotoxic T lymphocytes (CTL) activity and macrophages' bacteriolytic capability was studied in vitro after 1 hour of treatment. The proliferative response of lymphocytes to concanavalin A and lipopolysaccharide was not affected by OTA; the cytotoxic activity of NK cells was dose-dependent decreased; the CTL activity was significantly decreased at the lowest concentration; the bacteriolytic activity of macrophages varied only slightly. These in vitro results reproduced, at least in part, some effects detected previously in vivo. The protein synthesis inhibition and the oxidative metabolism of OTA coupled to the prostaglandin synthesis are probably implicated in NK cells' toxicity, because the effects were reverted by the addition of phenylalanine or piroxicam to the culture medium. The induction of apoptosis seems to be the principal mechanism of action in the CTL effect. The intracellular concentration of OTA after 1 hour was analysed by HPLC and was found to be proportional to the quantity of OTA added to the culture medium for the three cell types; the presence of phenylalanine and piroxicam on the culture medium did not change the intracellular OTA concentration.

Key Words: apoptosis • immunotoxicity • in vitro • ochratoxin A • phenylalanine • piroxicam

Human & Experimental Toxicology, Vol. 24, No. 9, 459-466 (2005)
DOI: 10.1191/0960327105ht554oa


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