Interaction of 2′R-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
Affiliations
Zelma Faisal
Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
Diána Derdák
János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary
Beáta Lemli
János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary
Sándor Kunsági-Máté
János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary
Mónika Bálint
Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
Csaba Hetényi
Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
Rita Csepregi
János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary
Tamás Kőszegi
János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary
Franziska Sueck
Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstr. 45, 48149 Münster, Germany
Benedikt Cramer
Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstr. 45, 48149 Münster, Germany
Hans-Ulrich Humpf
Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstr. 45, 48149 Münster, Germany
Miklós Poór
Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary
Ochratoxin A (OTA) is a nephrotoxic mycotoxin. Roasting of OTA-contaminated coffee results in the formation of 2′R-ochratoxin A (2′R-OTA), which appears in the blood of coffee drinkers. Human serum albumin (HSA) binds 2′R-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 2′R-OTA (verses OTA) in HSA and the displacing effects of site markers to explore which molecules can interfere with its albumin-binding. Affinity of 2′R-OTA toward albumins from various species (human, bovine, porcine and rat) was tested to evaluate the interspecies differences regarding 2′R-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 2′R-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 2′R-OTA than OTA from HSA. Fluorescence and binding constants of 2′R-OTA-albumin and OTA-albumin complexes showed different tendencies. Albumin significantly decreased the cytotoxicity of ochratoxins. 2′R-OTA, even at sub-toxic concentrations, increased the toxic action of OTA.
