In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells

In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells
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DOI:
10.1016/j.tiv.2005.08.003
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发表时间:
2006-04-01
影响因子:
3.2
通讯作者:
O'Brien, E
O'Brien, E
中科院分区:
医学3区
文献类型:
--
作者:
Heussner, AH;Dietrich, DR;O'Brien, E

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迄今为止,已知有数百种霉菌毒素,其中许多毒素在人类和动物健康方面受到极大关注,因为它们经常在植物衍生产品中检测到。根据环境和基质条件,多种霉菌毒素可能同时出现。考虑到这种同时产生的情况,人类和动物很可能总是接触混合物而不是单独的化合物。因此,未来的风险评估应考虑混合物毒性数据。对于赭曲霉毒素 A (OTA)、赭曲霉毒素 B (OTB)、柑橘素 (CIT) 和偶尔展青霉素 (PAT) 来说尤其如此,因为它们都是由许多青霉属和曲霉属物种产生的。因此,选择这四种毒素来研究体外相互作用效应,使用成熟的猪肾细胞系 LLC-PK1 和 MTT 还原试验作为细胞毒性终点。通过应用逐步方法来测试组合毒性,使用各种全因子以及中心复合实验设计,评估了这四种毒素的相互作用(协同)细胞毒性作用。本研究获得的结果证实了 CIT 和 OTA 以及可能的其他霉菌毒素在肾源细胞中潜在的相互作用(协同)作用。 (c) 2005 Elsevier Ltd. 保留所有权利。
Hundreds of mycotoxins are known to date and many of them are of great interest with regard to human and animal health since they are detected frequently in plant-derived products. Various mycotoxins may occur simultaneously, depending on the environmental and substrate conditions. Considering this coincident production, it is very likely, that humans and animals are always exposed to mixtures rather than to individual compounds. Therefore, future risk assessments should consider mixture toxicity data. This is particularly true for ochratoxin A (OTA), ochratoxin B (OTB), citrinin (CIT) and occasionally for patulin (PAT) as they are all produced by a number of Penicillium and Aspergillus species. Therefore, these four toxins were chosen to study the interactive effects in vitro, using the well-established porcine renal cell line LLC-PK1 and the MTT reduction test as a cytotoxicity, endpoint. By application of a step-wise approach to test combination toxicity, using various full factorial as well as a central composite experimental designs, the interactive (synergistic) cytotoxic effects of the these four toxins were assessed. The results obtained in this study confirm a potential for interactive (synergistic) effects of CIT and OTA and possibly other mycotoxins in cells of renal origin. (c) 2005 Elsevier Ltd. All rights reserved.