In Vitro Evaluation of the Individual and Combined Cytotoxic and Estrogenic Effects of Zearalenone, Its Reduced Metabolites, Alternariol, and Genistein.

Adrienn Balázs,Rita Csepregi,Miklós Poór,István Szabó,Balázs Kriszt,Tamás Kőszegi,Zelma Faisal

doi:10.3390/ijms22126281

Abstract

Mycotoxins are toxic metabolites of filamentous fungi. Previous studies demonstrated the co-occurrence of Fusarium and Alternaria toxins, including zearalenone (ZEN), ZEN metabolites, and alternariol (AOH). These xenoestrogenic mycotoxins appear in soy-based meals and dietary supplements, resulting in the co-exposure to ZEN and AOH with the phytoestrogen genistein (GEN). In this study, the cytotoxic and estrogenic effects of ZEN, reduced ZEN metabolites, AOH, and GEN are examined to evaluate their individual and combined impacts. Our results demonstrate that reduced ZEN metabolites, AOH, and GEN can aggravate ZEN-induced toxicity; in addition, the compounds tested exerted mostly synergism or additive combined effects regarding cytotoxicity and/or estrogenicity. Therefore, these observations underline the importance and the considerable risk of mycotoxin co-exposure and the combined effects of mycoestrogens with phytoestrogens.

Highlights

Mycotoxins, the toxic secondary metabolites of filamentous fungi, are common contaminants in food and animal feed [1]
The cytotoxic effects of ZEN, its metabolites, and AOH were tested on a human cervical cancer cell line (HeLa)
The cytotoxicity of mycotoxins was evaluated based on the ATP levels/well [46]

Summary

Introduction

Mycotoxins, the toxic secondary metabolites of filamentous fungi, are common contaminants in food and animal feed [1]. Chronic exposure to mycotoxins poses a significant health risk for both animals and humans [2]. Zearalenone (ZEN; Figure 1) is a Fusariumderived xenoestrogenic mycotoxin, which frequently occurs in grains (especially in maize) and in cereal-based products [3]. ZEN is extensively biotransformed via phase I and II reactions [4]. Hydroxysteroid dehydrogenase enzymes can reduce ZEN, resulting in the formation of α- and β-zearalenols (α- and β-ZELs, respectively; Figure 1) [3,4]. ZEN and ZELs can be further reduced to zearalanone (ZAN) and zearalanols (α- and β-ZALs), respectively [3,4]. Thereafter, ZEN and its reduced metabolites are subjected to glucuronide or sulfate conjugations [4]. Among the reduced ZEN metabolites, α-ZEL and α-ZAL exert

Methods

Results

Conclusion