Zearalenone Is Converted to a Potent Oestrogenic Metabolite by the Equine Hepatic Subcellular Fractions and Hepatocytes

Zearalenone (ZEA) is found in contaminated feeds and its oestrogenic effects depend on its biotransformation fate. The current study aimed to investigate the hepatic biotransformation of ZEA in horse by using freshly isolated hepatocytes and also hepatic subcellular fractions. ZEA was incubated with hepatocytes and hepatic intracellular subfractions in the presence of nicotinamide dinucleotide phosphate (NADPH), and the products were determined by high-performance liquid chromatography. Moreover, in the presence of uridine diphosphate glucuronic acid (UDPGA), the rate of glucuronidation for ZEA and its products were estimated. We found that α-zearalenol (α-ZOL) was the major hepatic metabolite of ZEA. The enzymatic kinetics analyses indicated that the α-ZOL production by hepatocytes and microsomal fractions were three and two-fold higher than the β-zearalenol (β-ZOL) production, respectively. The postmitochondrial fraction was able to convert the ZEA into only αZOL and 5-fold less than the microsomal fraction and hepatocytes. ZEA and α-ZOL were entirely conjugated with glucuronic acid at the lower concentrations; while at concentrations higher than 50 μM, ZEA is conjugated 2–3 times than α-ZOL. Our data suggest that the hepatic biotransformation of ZEA results in bioactivation and formation of potent oestrogenic metabolite. Moreover, at the relevant concentrations, ZEA and α-ZOL are entirely conjugated with glucuronic acid that may prolong its presence in the body.