Interaction of Citrinin with Human Serum Albumin

Abstract

Citrinin (CIT) is a mycotoxin produced by several Aspergillus, Penicillium, and Monascus species. CIT occurs worldwide in different foods and drinks and causes health problems for humans and animals. Human serum albumin (HSA) is the most abundant plasma protein in human circulation. Albumin forms stable complexes with many drugs and xenobiotics; therefore, HSA commonly plays important role in the pharmacokinetics or toxicokinetics of numerous compounds. However, the interaction of CIT with HSA is poorly characterized yet. In this study, the complex formation of CIT with HSA was investigated using fluorescence spectroscopy and ultrafiltration techniques. For the deeper understanding of the interaction, thermodynamic, and molecular modeling studies were performed as well. Our results suggest that CIT forms stable complex with HSA (logK ~ 5.3) and its primary binding site is located in subdomain IIA (Sudlow’s Site I). In vitro cell experiments also recommend that CIT-HSA interaction may have biological relevance. Finally, the complex formations of CIT with bovine, porcine, and rat serum albumin were investigated, in order to test the potential species differences of CIT-albumin interactions.

Interactions of zearalenone and its reduced metabolites α-zearalenol and β-zearalenol with serum albumins: species differences, binding sites, and thermodynamics

“…2. In a concentration-dependent fashion, each tested mycotoxin induced the decrease of fluorescence at 340 nm (emission maximum of albumins), resulted from the quenching effects of ZEN and ZELs on albumins and suggesting the formation of mycotoxin-albumin complexes (Poór et al 2015(Poór et al , 2017a(Poór et al , 2017b (Fig. 3) clearly indicate the different binding affinities of these mycotoxins towards HSA.…”

“…Therefore, it is expected that their biological behaviors, such as their ligand binding properties, are usually very similar. Indeed, the mycotoxin aflatoxin B1 and citrinin bind to different albumins with similar affinity (Poór et al 2015(Poór et al , 2017a). Nevertheless, some ligands, such as ochratoxin A, show marked species-dependence (Poór et al 2014;Kőszegi and Poór 2016).…”

“…Since the albumin-bound warfarin expresses much stronger fluorescence than free warfarin, the increase in the HSA-bound warfarin significantly enhance its fluorescence at 379 nm (Poór et al 2015(Poór et al , 2017a(Poór et al , 2017b. To test whether or not ZELs exert similar effects, ZELs at increasing concentrations (0-10 μmol/L) were added to warfarin (1 μmol/L; 0.308 mg/L) and HSA (3.5 μmol/L; 0.233 g/L) in PBS.…”

“…However, recent studies highlighted the importance of a third binding site located in subdomain IB (Heme binding site) (Fanali et al 2012;Zsila 2013). As previous studies demonstrated, many mycotoxins (e.g., aflatoxins, citrinin, deoxynivalenol, ochratoxins, patulin, and ZEN) form stable non-covalent complexes with albumins (Poór et al 2012(Poór et al , 2015(Poór et al , 2017a(Poór et al , 2017bLi et al 2013;Perry et al 2003;Yuqin et al 2014). Some of these interaction could be of high toxicological importance.…”

“…Some of these interaction could be of high toxicological importance. Aflatoxins, deoxynivalenol, and patulin form less stable complexes with human albumin (K ~ 4 L/mol) (Poór et al 2017a;Li et al 2013;Yuqin et al 2014) than citrinin and ZEN (K ~ 10 5 L/mol) (Poór et al 2015(Poór et al , 2017b, while the stability of ochratoxin A-albumin complex is extremely high (K ~ 10 7 L/mol) (Kőszegi and Poór 2016;Sueck et al, 2018).…”