Baudrimont I, Ahouandjivo R, Creppy E E
Laboratoire de Toxicologie et d'Hygiène appliquée, UFR des Sciences Pharmaceutiques, Université Victor Segalen Bordeaux 2, France.
Chem Biol Interact. 1997 Apr 18;104(1):29-40. doi: 10.1016/s0009-2797(97)03764-2.
Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceus as well as other moulds. This mycotoxin contaminates animal feed and food and is nephrotoxic for all animal species studied so far. OTA is immunosuppressive, genotoxic, teratogenic and carcinogenic. It is a structural analogue of phenylalanine and contains a chlorinated dihydroisocoumarinic moiety. Ochratoxin A inhibits protein synthesis by competition with phenylalanine in the phenylalanine-tRNA aminoacylation reaction. Recently lipid peroxidation induced by OTA has been reported, indicating that the lesions induced by this toxin could also be related to oxidative damage. An attempt to prevent its toxic effect, mainly the lipid peroxidation, has been made using aspartame (L-aspartyl-L-phenylalanine methyl ester) a structural analogue of both OTA and phenylalanine, piroxicam, a non steroidal anti-inflammatory drug and superoxide dismutase+catalase (endogenous oxygen radical scavengers). Lipid peroxidation was assayed in monkey kidney cells (Vero cells) treated by increasing concentrations of OTA (5-50 microM). After 24 h incubation OTA induced lipid peroxidation in Vero cells in a concentration dependent manner, as measured by malonaldehyde (MDA) production. The MDA production, in Vero cells, was significantly increased by 50.5% from 694.1 +/- 21.0 to 1041.5 +/- 23.5 pmol/mg of protein. In the presence of superoxide dismutase (SOD)+catalase (25 micrograms/ml each) the MDA production induced by OTA was significantly decreased. At 50 microM of OTA concentration (optimal production of MDA) the MDA production decreased from 1041.5 +/- 23.5 to 827.5 +/- 21.3 pmol/mg of protein. SOD and catalase, when applied prior to the toxin, seemed to prevent lipid peroxidation more efficiently than piroxicam (at a ten-fold higher concentration than OTA) and aspartame (at equimolar concentration). These molecules also partially prevented the OTA-induced leakage of MDA in the culture medium.
赭曲霉毒素A（OTA）是由赭曲霉以及其他霉菌产生的一种霉菌毒素。这种霉菌毒素会污染动物饲料和食物，并且对迄今为止所研究的所有动物物种都具有肾毒性。OTA具有免疫抑制、基因毒性、致畸性和致癌性。它是苯丙氨酸的结构类似物，含有一个氯化二氢异香豆素部分。赭曲霉毒素A通过在苯丙氨酸 - tRNA氨基酰化反应中与苯丙氨酸竞争来抑制蛋白质合成。最近有报道称OTA可诱导脂质过氧化，这表明该毒素引起的损伤也可能与氧化损伤有关。人们尝试使用阿斯巴甜（L - 天冬氨酰 - L - 苯丙氨酸甲酯）（OTA和苯丙氨酸的结构类似物）、吡罗昔康（一种非甾体抗炎药）以及超氧化物歧化酶 + 过氧化氢酶（内源性氧自由基清除剂）来预防其毒性作用，主要是脂质过氧化。在用递增浓度（5 - 50微摩尔）的OTA处理的猴肾细胞（Vero细胞）中检测脂质过氧化。孵育24小时后，OTA以浓度依赖性方式诱导Vero细胞中的脂质过氧化，通过丙二醛（MDA）生成量来衡量。Vero细胞中的MDA生成量从694.1±21.0显著增加到1041.5±23.5皮摩尔/毫克蛋白质，增加了约50.5%。在存在超氧化物歧化酶（SOD）+ 过氧化氢酶（各25微克/毫升）的情况下，OTA诱导的MDA生成量显著降低。在OTA浓度为50微摩尔（MDA生成量最佳）时，MDA生成量从1041.5±23.5降至827.5±21.3皮摩尔/毫克蛋白质。当在毒素处理之前应用SOD和过氧化氢酶时，它们似乎比吡罗昔康（浓度比OTA高十倍）和阿斯巴甜（等摩尔浓度）更有效地预防脂质过氧化。这些分子还部分地防止了OTA诱导的培养基中MDA的泄漏。
