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

doi:10.3390/toxins10090353

Abstract

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.

Highlights

IntroductionOchratoxin AA(OTA;(OTA; Figure is a widespread mycotoxin produced by Aspergillus and Ochratoxin Figure 1) is1)a widespread mycotoxin produced by Aspergillus and PenicilliumPenicillium species [1].It is present in several foods and drinks, mainly in cereals and cereal products species [1]
We demonstrate that albumin significantly alleviate the cytotoxicity of 20 R-OTA in MDCK cell line
Binding of 20 R-OTA albumin (HSA) binds R-OTA (and OTA) to Human serum albumin (HSA) Based on Modeling Studies

Summary

Introduction

IntroductionOchratoxin AA(OTA;(OTA; Figure is a widespread mycotoxin produced by Aspergillus and Ochratoxin Figure 1) is1)a widespread mycotoxin produced by Aspergillus and PenicilliumPenicillium species [1].It is present in several foods and drinks, mainly in cereals and cereal products species [1]. (OTA; Figure is a widespread mycotoxin produced by Aspergillus and Ochratoxin Figure 1) is). A widespread mycotoxin produced by Aspergillus and Penicillium. It is present in several foods and drinks, mainly in cereals and cereal products species [1] It is present in several foods and drinks, mainly in cereals and cereal products and in but alsobeer, in coffee, beer, wine, spices[2,3]. Dueoccurrence to its wide occurrence and stability high thermal coffee, wine, spices and cocoa to [2,3]. Its wide and high thermal [4,5], stability [4,5], eradication It is present in several foods and drinks, mainly in cereals and cereal products and in but alsobeer, in coffee, beer, wine, spices[2,3]. andDue cocoa

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