Interaction of 2R-ochratoxin a with serum albumins: Binding site, effects of site markers, thermodynamics, species differences of albumin-binding, and influence of albumin on its toxicity in MDCK cells

Zelma Faisal, Diána Derdák, Beáta Lemli, Sándor Kunsági-Máté, Mónika Bálint, Csaba Hetényi, Rita Csepregi, Tamás Kőszegi, Franziska Sueck, Benedikt Cramer, Hans Ulrich Humpf, Miklós Poór

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Ochratoxin A (OTA) is a nephrotoxic mycotoxin. Roasting of OTA-contaminated coffee results in the formation of 2R-ochratoxin A (2R-OTA), which appears in the blood of coffee drinkers. Human serum albumin (HSA) binds 2R-OTA (and OTA) with high affinity; therefore, albumin may influence the tissue uptake and elimination of ochratoxins. We aimed to investigate the binding site of 2R-OTA (verses OTA) in HSA and the displacing effects of site markers to explore which molecules can interfere with its albumin-binding. Affinity of 2R-OTA toward albumins from various species (human, bovine, porcine and rat) was tested to evaluate the interspecies differences regarding 2R-OTA-albumin interaction. Thermodynamic studies were performed to give a deeper insight into the molecular background of the complex formation. Besides fluorescence spectroscopic and modeling studies, effects of HSA, and fetal bovine serum on the cytotoxicity of 2R-OTA and OTA were tested in MDCK kidney cell line in order to demonstrate the influence of albumin-binding on the cellular uptake of ochratoxins. Site markers displaced more effectively 2R-OTA than OTA from HSA. Fluorescence and binding constants of 2R-OTA-albumin and OTA-albumin complexes showed different tendencies. Albumin significantly decreased the cytotoxicity of ochratoxins. 2R-OTA, even at sub-toxic concentrations, increased the toxic action of OTA.

Original languageEnglish
Article number353
JournalToxins
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 2018

Keywords

  • 2′r-ochratoxin A
  • Albumin-ligand interaction
  • Cellular toxicity
  • Ochratoxin A
  • Serum albumin
  • Species differences

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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