Unraveling Interspecies Differences in the Phase I Hepatic Metabolism of Alternariol and Alternariol Monomethyl Ether: Closing Data Gaps for a Comprehensive Risk Assessment
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View abstract on PubMed
Summary
This summary is machine-generated.This study investigated the metabolism of Alternaria mycotoxins alternariol (AOH) and alternariol 9-O-monomethyl ether (AME) using liver microsomes. Findings reveal interspecies differences in their phase I metabolism, crucial for understanding toxicokinetics.
Area Of Science
- Environmental Chemistry
- Toxicology
- Biochemistry
Background
- Alternaria mycotoxins, specifically alternariol (AOH) and alternariol 9-O-monomethyl ether (AME), are common food contaminants.
- While known for in vitro adverse effects, their toxicokinetics, particularly metabolism, are not well understood.
Purpose Of The Study
- To elucidate the qualitative and quantitative aspects of phase I metabolism for AOH and AME.
- To investigate interspecies differences in the metabolic pathways and rates of these mycotoxins.
Main Methods
- Incubation of AOH and AME with NADPH-fortified porcine, rat, and human liver microsomes.
- Monitoring parent toxin concentration decline using liquid chromatography coupled to tandem mass spectrometry.
- Analyzing metabolic products using high-resolution mass spectrometry.
Main Results
- Quantification of AOH and AME concentrations allowed calculation of hepatic intrinsic clearance rates.
- Identified distinct patterns and rates of phase I metabolism across different species (porcine, rat, human).
Conclusions
- The study provides crucial data on the hepatic metabolism of AOH and AME.
- Findings contribute to physiologically based toxicokinetic modeling for predicting mycotoxin concentrations in organs.
- Enhanced understanding of mycotoxin mode of action and potential adverse health effects.
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