Interaction of the mycotoxin metabolite dihydrocitrinone with serum albumin

Zelma Faisal, Virág Vörös, Beáta Lemli, Diána Derdák, S. Kunsági-Máté, Mónika Bálint, C. Hetényi, Rita Csepregi, T. Kőszegi, Dominik Bergmann, Franziska Sueck, Hans Ulrich Humpf, Florian Hübner, Miklós Poór

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalMycotoxin Research
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Mycotoxins
Metabolites
Serum Albumin
Citrinin
Albumins
Circular Dichroism
dihydrocitrinone
Monascus
Fluorescence
Spices
Madin Darby Canine Kidney Cells
Nuts
Molecular modeling
Aspergillus
Penicillium
Fluorescence Spectrometry
Fluorescence spectroscopy
Tissue Distribution
Biotransformation
Fruits

Keywords

  • Albumin-ligand interaction
  • Citrinin
  • Dihydrocitrinone
  • Fluorescence spectroscopy
  • Serum albumin

ASJC Scopus subject areas

  • Biotechnology
  • Microbiology
  • Toxicology

Cite this

Interaction of the mycotoxin metabolite dihydrocitrinone with serum albumin. / Faisal, Zelma; Vörös, Virág; Lemli, Beáta; Derdák, Diána; Kunsági-Máté, S.; Bálint, Mónika; Hetényi, C.; Csepregi, Rita; Kőszegi, T.; Bergmann, Dominik; Sueck, Franziska; Humpf, Hans Ulrich; Hübner, Florian; Poór, Miklós.

In: Mycotoxin Research, 01.01.2018.

Research output: Contribution to journalArticle

Faisal, Z, Vörös, V, Lemli, B, Derdák, D, Kunsági-Máté, S, Bálint, M, Hetényi, C, Csepregi, R, Kőszegi, T, Bergmann, D, Sueck, F, Humpf, HU, Hübner, F & Poór, M 2018, 'Interaction of the mycotoxin metabolite dihydrocitrinone with serum albumin', Mycotoxin Research. https://doi.org/10.1007/s12550-018-0336-z
Faisal, Zelma ; Vörös, Virág ; Lemli, Beáta ; Derdák, Diána ; Kunsági-Máté, S. ; Bálint, Mónika ; Hetényi, C. ; Csepregi, Rita ; Kőszegi, T. ; Bergmann, Dominik ; Sueck, Franziska ; Humpf, Hans Ulrich ; Hübner, Florian ; Poór, Miklós. / Interaction of the mycotoxin metabolite dihydrocitrinone with serum albumin. In: Mycotoxin Research. 2018.
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abstract = "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.",
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AU - Faisal, Zelma

AU - Vörös, Virág

AU - Lemli, Beáta

AU - Derdák, Diána

AU - Kunsági-Máté, S.

AU - Bálint, Mónika

AU - Hetényi, C.

AU - Csepregi, Rita

AU - Kőszegi, T.

AU - Bergmann, Dominik

AU - Sueck, Franziska

AU - Humpf, Hans Ulrich

AU - Hübner, Florian

AU - Poór, Miklós

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N2 - 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.

AB - 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.

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