Citrinin (CIT) is a nephrotoxic mycotoxin produced by Penicillium, Monascus, and Aspergillus species. CIT appears as a contaminant in cereals, cereal-based products, fruits, nuts, and spices. During the biotransformation of CIT, its major urinary metabolite dihydrocitrinone (DHC) is formed. Albumin interacts with several compounds (including mycotoxins) affecting their tissue distribution and elimination. CIT-albumin interaction is known; however, the complex formation of DHC with albumin has not been reported previously. In this study, we aimed to investigate the interaction of DHC with albumin, employing fluorescence spectroscopy, circular dichroism, and molecular modeling studies. Furthermore, species differences and thermodynamics of the interaction as well as the effects of albumin on the acute in vitro toxicity of DHC and CIT were also tested. Our main observations/conclusions are as follows: (1) Fluorescence signal of DHC is strongly enhanced by albumin. (2) Formation of DHC-albumin complexes is supported by both fluorescence spectroscopic and circular dichroism studies. (3) DHC forms similarly stable complexes with human albumin (K~10⁵ L/mol) as CIT. (4) DHC-albumin interaction did not show significant species differences (tested with human, bovine, porcine, and rat albumins). (5) Based on modeling studies and investigations with site markers, DHC occupies the Heme binding site (subdomain IB) on human albumin. (6) The presence of albumin significantly decreased the acute in vitro cytotoxic effects of both DHC and CIT on MDCK cell line.

中文翻译：

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霉菌毒素代谢产物二氢胞苷与血清白蛋白的相互作用。

Citrinin（CIT）是由青霉菌，红曲霉和曲霉产生的一种肾毒性霉菌毒素种类。CIT在谷物，谷物产品，水果，坚果和香料中似乎是一种污染物。在CIT的生物转化过程中，形成了其主要的尿代谢物二氢西苯醌（DHC）。白蛋白与几种化合物（包括霉菌毒素）相互作用，影响其组织分布和清除。CIT-白蛋白相互作用是已知的。但是，DHC与白蛋白的复合物形成尚未见报道。在这项研究中，我们旨在利用荧光光谱，圆二色性和分子模型研究来研究DHC与白蛋白的相互作用。此外，还测试了相互作用的物种差异和热力学以及白蛋白对DHC和CIT的急性体外毒性的影响。我们的主要观察结果/结论如下：（1）DHC的荧光信号被白蛋白强烈增强。（2）DHC-白蛋白复合物的形成得到荧光光谱和圆二色性研究的支持。（3）DHC与人白蛋白形成类似的稳定复合物（ķ〜10 ⁵  L /摩尔）为CIT。（4）DHC与白蛋白的相互作用没有显示出明显的物种差异（用人，牛，猪和大鼠白蛋白进行了测试）。（5）基于建模研究和使用位点标记的研究，DHC占据了人白蛋白上的血红素结合位点（亚结构域IB）。（6）白蛋白的存在显着降低了DHC和CIT对MDCK细胞系的急性体外细胞毒性作用。