Interactions of zearalanone, α-zearalanol, ß-zearalanol, zearalenone-14-sulfate, and zearalenone-14-glucoside with serum albumin.

The xenoestrogenic mycotoxin zearalenone is a Fusarium-derived food and feed contaminant. In mammals, the reduced (e.g., zearalanone, α-zearalanol, and ß-zearalanol) and conjugated (e.g., zearalenone-14-sulfate) metabolites of zearalenone are formed. Furthermore, filamentous fungi and plants are also able to convert zearalenone to conjugated derivatives, including zearalenone-14-sulfate and zearalenone-14-glucoside, respectively. Serum albumin is the dominant plasma protein in the circulation; it interacts with certain mycotoxins, affecting their toxicokinetics. In a previous investigation, we demonstrated the remarkable species differences regarding the albumin binding of zearalenone and zearalenols. In the current study, the interactions of zearalanone, α-zearalanol, ß-zearalanol, zearalenone-14-sulfate, and zearalenone-14-glucoside with human, bovine, porcine, and rat serum albumins were examined, employing fluorescence spectroscopy and affinity chromatography. Zearalanone, zearalanols, and zearalenone-14-sulfate form stable complexes with albumins tested (K = 9.3 × 103 to 8.5 × 105 L/mol), while the albumin binding of zearalenone-14-glucoside seems to be weak. Zearalenone-14-sulfate formed the most stable complexes with albumins examined. Considerable species differences were observed in the albumin binding of zearalenone metabolites, which may have a role in the interspecies differences regarding the toxicity of zearalenone.

Probing the Interactions of Ochratoxin B, Ochratoxin C, Patulin, Deoxynivalenol, and T-2 Toxin with Human Serum Albumin.

Ochratoxins, patulin, deoxynivalenol, and T-2 toxin are mycotoxins, and common contaminants in food and drinks. Human serum albumin (HSA) forms complexes with certain mycotoxins. Since HSA can affect the toxicokinetics of bound ligand molecules, the potential interactions of ochratoxin B (OTB), ochratoxin C (OTC), patulin, deoxynivalenol, and T-2 toxin with HSA were examined, employing spectroscopic (fluorescence, UV, and circular dichroism) and ultrafiltration techniques. Furthermore, the influence of albumin on the cytotoxicity of these xenobiotics was also evaluated in cell experiments. Fluorescence studies showed the formation of highly stable OTB-HSA and OTC-HSA complexes. Furthermore, fluorescence quenching and circular dichroism measurements suggest weak or no interaction of patulin, deoxynivalenol, and T-2 toxin with HSA. In ultrafiltration studies, OTB and OTC strongly displaced the Sudlow's site I ligand warfarin, while other mycotoxins tested did not affect either the albumin binding of warfarin or naproxen. The presence of HSA significantly decreased or even abolished the OTB- and OTC-induced cytotoxicity in cell experiments; however, the toxic impacts of patulin, deoxynivalenol, and T-2 toxin were not affected by HSA. In summary, the complex formation of OTB and OTC with albumin is relevant, whereas the interactions of patulin, deoxynivalenol, and T-2 toxin with HSA may have low toxicological importance.

Interaction of the mycotoxin metabolite dihydrocitrinone with serum albumin.

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.