Alterations induced in vitro by ochratoxin A in rat lymphoid cells
Alterations induced in vitro by ochratoxin A in rat lymphoid cells
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DOI：
10.1191/0960327105ht554oa
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发表时间：
2005-09-01
影响因子：
2.8
通讯作者：
de Cerain, AL
中科院分区：
文献类型：
--
作者：
Alvarez-Erviti, L;Leache, C;de Cerain, AL
赭曲霉毒素A （OTA）是一种肾毒性真菌毒素，由青霉属和曲霉属产生，作为一种天然污染物存在于食品和饲料中。它能改变动物的免疫功能，抑制体外淋巴细胞的增殖反应。研究了OTA（0.5、2、20 μ M）在体外作用1 h后对淋巴细胞增殖反应、自然杀伤细胞（nk）活性、细胞毒性T淋巴细胞（CTL）活性和巨噬细胞溶菌能力的毒性作用。淋巴细胞对刀豆蛋白A和脂多糖的增殖反应不受OTA的影响；NK细胞毒活性呈剂量依赖性降低；最低浓度下CTL活性显著降低；巨噬细胞的溶菌活性变化不大。这些体外实验结果至少部分再现了先前在体内检测到的一些效果。由于在培养基中加入苯丙氨酸或吡罗西康后，这种作用被逆转，因此蛋白质合成抑制和OTA氧化代谢与前列腺素合成耦合可能与NK细胞的毒性有关。诱导细胞凋亡似乎是CTL效应的主要作用机制。高效液相色谱法测定三种细胞1小时后的OTA细胞内浓度，发现其与三种细胞类型的培养基中添加的OTA量成正比；苯丙氨酸和吡罗西康的存在对细胞内OTA浓度没有影响。
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 mu M) in lympho proliferative response, natural killer (N.K) 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 inhibi-tion 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.