Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624 Pécs, Hungary.
Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary.
Biomolecules. 2022 Aug 11;12(8):1106. doi: 10.3390/biom12081106.
Beauvericin (BEA), cyclopiazonic acid (CPA), and sterigmatocystin (STC) are emerging mycotoxins. They appear as contaminants in food and animal feed, leading to economic losses and health risks. Human serum albumin (HSA) forms stable complexes with certain mycotoxins, including ochratoxins, alternariol, citrinin, and zearalenone. HSA binding can influence the toxicokinetics of xenobiotics, and albumin can also be considered and applied as a relatively cheap affinity protein. Therefore, we examined the potential interactions of BEA, CPA, and STC with HSA employing fluorescence spectroscopy, ultracentrifugation, ultrafiltration, and molecular modeling. Spectroscopic and ultracentrifugation studies demonstrated the formation of low-affinity BEA-HSA ( ≈ 10 L/mol) and moderately strong CPA-HSA and STC-HSA complexes ( ≈ 10 L/mol). In ultrafiltration experiments, CPA slightly displaced each site marker (warfarin, naproxen, and camptothecin) tested, while BEA and STC did not affect significantly the albumin binding of these drugs. Modeling studies suggest that CPA occupies Sudlow's site I, while STC binds to the Heme site (FA1) on HSA. Considering the interactions of CPA with the site markers, the CPA-HSA interaction may have toxicological importance.
展青霉素（BEA）、环匹阿尼酸（CPA）和桔青霉素（STC）是新兴的霉菌毒素。它们作为污染物出现在食品和动物饲料中，导致经济损失和健康风险。人血清白蛋白（HSA）与某些霉菌毒素（包括赭曲毒素、交链孢酚、桔青霉素和玉米赤霉烯酮）形成稳定的复合物。HSA 结合可以影响外源性物质的毒代动力学，并且白蛋白也可以被认为是一种相对廉价的亲和蛋白。因此，我们使用荧光光谱法、超速离心、超滤和分子建模研究了 BEA、CPA 和 STC 与 HSA 的潜在相互作用。光谱和超速离心研究表明，形成了低亲和力的 BEA-HSA（≈10 L/mol）和中等强度的 CPA-HSA 和 STC-HSA 复合物（≈10 L/mol）。在超滤实验中，CPA 轻微置换了每种位点标记物（华法林、萘普生和喜树碱），而 BEA 和 STC 对这些药物与白蛋白的结合没有显著影响。建模研究表明，CPA 占据了 Sudlow 的位点 I，而 STC 结合到 HSA 上的血红素位点（FA1）。考虑到 CPA 与位点标记物的相互作用，CPA-HSA 相互作用可能具有毒理学意义。
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