An in vitromodel to quantify interspecies differences in kinetics for intestinal microbial bioactivation and detoxification of zearalenone. (2020)

• Record Type: Journal Article
• Authors: Mendez-Catala, Diana M.; Spenkelink, Albertus; Rietjens, Ivonne M.C.M.; Beekmann, Karsten
• Is Part Of: Toxicology reports. Volume 7(2020)
• Page Start: 938
• Page End: 946
• Publication Date: 2020
• Subjects: α-ZEL α-zearalenol -- β-ZEL β-zearalenol -- ER estrogen receptor -- kcat catalytic efficiency -- RP relative potency -- UPLC-PDA ultra-performance liquid chromatography method with diode array detection -- LC–MS/MS liquid chromatography tandem mass spectrometry -- ZEN zearalenone; Intestinal microbiota -- Bioactivation -- Detoxification -- Zearalenone -- Interspecies differences; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2020.07.010
• Languages: English
• ISSNs: 2214-7500

Abstract

Graphical abstract: Highlights: An in vitro model for kinetic studies on microbial metabolism of ZEN was developed. The model identified substantial species differences in this microbial metabolism. This included marked species differences in preference for bioactivation to α-ZEL. Microbiota contribute to total ZEN metabolism in pigs and rats, while less in human. Results indicate a need for human-specific models for ZEN risk assessment. Abstract: Zearalenone (ZEN) is a mycotoxin known for its estrogenic activities. The metabolism of ZEN plays a role in the interspecies differences in sensitivity to ZEN, and is known to occur in the liver and via the intestinal microbiota, although the relative contribution of these two pathways remains to be characterized. In the present study a fecal in vitro model was optimized and used to quantify the interspecies differences in kinetics of the intestinal microbial metabolism of ZEN in rat, pig and human. Vmax, Km, and catalytic efficiencies (kcat ) were determined, and results obtained reveal that the kcat values for formation of α-ZEL and β-ZEL amounted to 0.73 and 0.12 mL/h/kg bw for human microbiota, 2.6 and 1.3 mL/h/kg bw for rat microbiota and 9.4 and 6.3 mL/h/kg bw for pig microbiota showing that overall ZEN metabolism increased in the order human < rat < pig microbiota. Expressed per kg bw the kcat for ZEN metabolism by the liver surpassed that of the intestinal microbiota in all three species. In conclusion, it is estimated that the activity of the intestinal colon microbiome may be up to 36 % of the activity of the liver, and that it can additionally contribute to the species differences in bioactivation and detoxification and thus the toxicity of ZEN in pigs and rats but not in humans. The results highlight the importance of the development of human specific models for the assessment of the metabolism of ZEN.