Cytotoxicity, inhibition of DNA and protein syntheses and oxidative damage in cultured cells exposed to zearalenone
Cytotoxicity, inhibition of DNA and protein syntheses and oxidative damage in cultured cells exposed to zearalenone
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DOI：
10.1016/j.tiv.2003.12.011
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发表时间：
2004-08-01
影响因子：
3.2
通讯作者：
Bacha, H
中科院分区：
文献类型：
--
作者：
Abid-Essefi, S;Ouanes, Z;Bacha, H
真菌毒素是饲料和食品中常见的各种真菌的有毒代谢产物，可对动物和人类造成非常严重的健康问题。玉米赤霉烯酮(Zearalenone，Zen)是一种由多种镰刀菌产生的真菌毒素，具有多种不良影响。事实上，Zen具有强烈的雌激素活性，与雌激素升高和生殖道的几种生理变化有关。此外，Zen还被证明具有肝脏毒性、血液毒性、免疫毒性和遗传毒性。Zen毒性的确切机制尚未完全确定。在与雌激素受体的结合中，Zen与17β-雌二醇竞争所产生的强烈的雌激素样作用通常被认为强调了Zen的大多数毒性作用，但单靠雌激素活性不能解释不同的和明显的不良反应。本研究的目的是确定在Zen诱导的毒性中是否涉及其他可能的机制。我们监测了暴露于ZEN的Vero和Caco-2细胞的细胞毒性、细胞周期扰动、蛋白质和DNA合成的抑制以及可能的氧化应激的后期标志丙二醛。我们的结果表明，Zen以浓度依赖的方式降低了与细胞周期扰动相关的细胞活力，抑制了蛋白质和DNA的合成，并增加了NMDA的形成。我们推测细胞毒性和氧化损伤是ZEN介导的毒性的额外机制。(C)2004爱思唯尔有限公司。保留所有权利。
Mycotoxins are toxic metabolites of various fungi commonly found in feed and foodstuff and can cause very serious health problems in animals as well as in humans.Zearalenone (ZEN), a mycotoxin produced by various Fusarium species has several adverse effects. Indeed, ZEN has strong estrogenic activity associated with hyperestrogenism and several physiological alterations of the reproductive tract. Moreover, ZEN was shown to be hepatotoxic, haematotoxic, immunotoxic and genotoxic. The exact mechanism of ZEN toxicity is not completely established. The observed strong estrogenic effect of ZEN resulting from its competition with 17beta-estradiol in the binding to estrogen receptors is generally considered to underline most toxic effects of ZEN, but estrogenic activity alone cannot explain the diverse and apparent adverse effects.The objective of the present study was to determine the involvement of other possible mechanisms in ZEN induced toxicity. Cytotoxicity, cell cycle perturbation, inhibition of protein and DNA synthesis as well as the presumed later marker of oxidative stress, malondialdehyde, were monitored in Vero and Caco-2 cells exposed to ZEN.Our results showed that ZEN reduces cell viability correlated to cell cycle perturbation, inhibits protein and DNA syntheses and increases NMDA formation in both cell lines in concentration-dependant manner. We assumed that cytotoxicity and oxidative damage are additional mechanisms of ZEN mediated toxicity. (C) 2004 Elsevier Ltd. All rights reserved.