Cytotoxicity and oxidative damage in kidney cells exposed to the mycotoxins ochratoxin A and citrinin: Individual and combined effects
Cytotoxicity and oxidative damage in kidney cells exposed to the mycotoxins ochratoxin A and citrinin: Individual and combined effects
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DOI：
10.1080/15376510701556682
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发表时间：
2008-01-01
影响因子：
3.2
通讯作者：
Bacha, Hassen
中科院分区：
文献类型：
--
作者：
Bouslimi, Amel;Ouannes, Zouhour;Bacha, Hassen
赭曲霉毒素A（OTA）和桔霉素（CTN）是两种真菌毒素，是非常常见的污染物，可在多种食品中同时出现。这两种真菌毒素都有几种毒性作用，但都具有显著的肾毒性潜力，因为据报道OTA和CTN是自然发生的人类和动物肾脏疾病的原因。考虑到OTA和CTN的伴随产生，人类和动物很可能总是暴露于混合物而不是单独的化合物。因此，本研究的目的是调查，使用肾细胞培养物（Vero细胞），细胞毒性和基本上氧化性细胞损伤（肾脏疾病的一个关键决定因素）是否增强了两种真菌毒素的组合相比，他们的效果单独。为此，我们使用三种不同的细胞活力测定法（MTT、台盼蓝和中性红）单独或组合评估了它们对细胞增殖的影响。此外，还通过测定丙二醛（MDA）水平和热休克蛋白Hsp 70的表达来研究氧化应激的作用。结果表明，OTA和CTN分别对培养的肾细胞产生中度和轻度的增殖抑制和氧化应激诱导。然而，当组合时，它们在抑制细胞活力以及诱导MDA水平和Hsp 70表达方面发挥显著增加。OTA和CTN组合效应明显具有协同性质。OTA和CTN同时观察到的氧化应激诱导增强可能与解释这些真菌毒素诱导的肾脏疾病的分子基础有关。
Ochratoxin A (OTA) and citrinin (CTN) are two mycotoxins, quite common contaminants, that can occur jointly in a wide range of food commodities. Both mycotoxins have several toxic effects but both share a significant nephrotoxic potential since OTA and CTN were reported to be responsible for naturally occurring human and animal kidney diseases.Considering the concomitant production of OTA and CTN, it is very likely that humans and animals are always exposed to the mixture rather than to individual compounds. Therefore, the aim of the present study was to investigate, using kidney cell culture (Vero cells), whether cytotoxicity and essentially oxidative cell damage (a key determinant of renal diseases) are enhanced by combination of both mycotoxins as compared to their effect separately. To this end, we have assessed their effects individually or combined on cell proliferation using three different cell viability assays (MTT, Trypan Blue, and Neutral Red). In addition, the role of oxidative stress was investigated by measuring the malondialdehyde (MDA) level and the expression of the heat shock protein Hsp 70.Our results clearly showed that cultured renal cells respond to OTA and CTN exposure by a moderate and weak inhibition of cell proliferation and induction of oxidative stress, respectively. However, when combined, they exert a significant increase in inhibition of cell viability as well as the induction of MDA level and Hsp 70 expression. OTA and CTN combination effects are clearly of synergistic nature. The enhanced induction of oxidative stress observed with OTA and CTN simultaneously could be relevant to explain the molecular basis of the renal diseases induced by these mycotoxins.