Abstract

Aflatoxins are widely spread mycotoxins produced mainly by Aspergillus species. Consumption of aflatoxin-contaminated foods and drinks causes serious health risks for people worldwide. It is well-known that the reactive epoxide metabolite of aflatoxin B1 (AFB1) forms covalent adducts with serum albumin. However, non-covalent interactions of aflatoxins with human serum albumin (HSA) are poorly characterized. Thus, in this study the complex formation of aflatoxins was examined with HSA applying spectroscopic and molecular modelling studies. Our results demonstrate that aflatoxins form stable complexes with HSA as reflected by binding constants between 2.1 × 104 and 4.5 × 104 dm3/mol. A binding free energy value of −26.90 kJ mol−1 suggests a spontaneous binding process between AFB1 and HSA at room-temperature, while the positive entropy change of 55.1 JK−1 mol−1 indicates a partial decomposition of the solvation shells of the interacting molecules. Modeling studies and investigations with site markers suggest that Sudlow’s Site I of subdomain IIA is the high affinity binding site of aflatoxins on HSA. Interaction of AFB1 with bovine, porcine, and rat serum albumins was also investigated. Similar stabilities of the examined AFB1-albumin complexes were observed suggesting the low species differences of the albumin-binding of aflatoxins.

Highlights

  • Mycotoxins are secondary metabolic products of filamentous fungi causing toxic actions in the body of animals and humans [1]

  • Our results demonstrate that aflatoxins form stable complexes with human serum albumin (HSA) occupying Sudlow’s Site I as high affinity binding site

  • The results of animal experiments with rats or pigs regarding the non-covalent albumin binding of aflatoxin B1 (AFB1) may be extrapolated to humans

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Summary

Introduction

Mycotoxins are secondary metabolic products of filamentous fungi causing toxic actions in the body of animals and humans [1]. B1 (AFB1), B2 (AFB2), G1 (AFG1), and G2 (AFG2); AFB2 and AFG2 are barely toxic unless they are oxidized to AFB1 and AFG1 in vivo [2]. Aflatoxins are found in different grains or foodstuffs (e.g., corn, peanuts, sorghum, and rice) causing serious health risks for people worldwide [3,4,5]. AFB1 is one of the best-known, widely spread mycotoxin produced mainly by Aspergillus flavus. The main target organ of AFB1 is the liver causing hepatocellular carcinoma; other toxic effects are attributed to AFB1, including lethal acute intoxication through highly contaminated food [2]. AFB1 has been classified as a Group I carcinogen by the International Agency for Research on Cancer

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