Identification of Beauvericin metabolites using rat and human liver microsomes and in vivo urinary excretion study in rats for biomonitoring application
Anushka Pandey , C. Yahavi , Manisha Bhateria , Abdul Rahman Khan , Sheelendra Pratap Singh
{"title":"Identification of Beauvericin metabolites using rat and human liver microsomes and in vivo urinary excretion study in rats for biomonitoring application","authors":"Anushka Pandey , C. Yahavi , Manisha Bhateria , Abdul Rahman Khan , Sheelendra Pratap Singh","doi":"10.1016/j.tiv.2024.105969","DOIUrl":null,"url":null,"abstract":"<div><div>Beauvericin (BEA), an emerging mycotoxin, belongs to a class characterized by a cyclic depsipeptide ring structure, commonly produced by fungal species like <em>Fusarium sp.</em> and <em>Beauveria bassiana</em>. BEA is known for contaminating cereals and grains (wheat, maize). Humans might be exposed to BEA through contaminated food. Biomonitoring is a valuable method for assessing environmental and occupational exposure to specific chemicals. These studies measure chemical biomarkers to quantify exposure for public health risk assessment. However, identifying specific and sensitive chemical biomarkers for BEA exposure remains challenging. In the present study, metabolites of BEA were identified through <em>in vitro</em> metabolism studies conducted in the rat (RLM) and human liver microsomes (HLM) using the liquid chromatography-high resolution mass spectrometry (LC-HRMS) technique. Seventeen metabolites were characterized, showcasing products of oxidation, reduction, and deamination reactions. Predominantly, oxidative metabolites resulting from mono‑oxygenation, di‑oxygenation, and tri‑oxygenation were observed. The metabolites in RLM primarily consisted of mono and di‑oxygenated forms, while in HLM, tri‑oxygenated and demethylated products were also found. Furthermore, <em>in vivo</em> excretion study in rat urine samples confirmed the presence of oxygenated metabolites detected in the <em>in vitro</em> samples. Consequently, the study suggests that oxygenated metabolites of BEA could serve as useful biomarkers for conducting future biomonitoring studies.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105969"},"PeriodicalIF":2.6000,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology in Vitro","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0887233324001991","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Beauvericin (BEA), an emerging mycotoxin, belongs to a class characterized by a cyclic depsipeptide ring structure, commonly produced by fungal species like Fusarium sp. and Beauveria bassiana. BEA is known for contaminating cereals and grains (wheat, maize). Humans might be exposed to BEA through contaminated food. Biomonitoring is a valuable method for assessing environmental and occupational exposure to specific chemicals. These studies measure chemical biomarkers to quantify exposure for public health risk assessment. However, identifying specific and sensitive chemical biomarkers for BEA exposure remains challenging. In the present study, metabolites of BEA were identified through in vitro metabolism studies conducted in the rat (RLM) and human liver microsomes (HLM) using the liquid chromatography-high resolution mass spectrometry (LC-HRMS) technique. Seventeen metabolites were characterized, showcasing products of oxidation, reduction, and deamination reactions. Predominantly, oxidative metabolites resulting from mono‑oxygenation, di‑oxygenation, and tri‑oxygenation were observed. The metabolites in RLM primarily consisted of mono and di‑oxygenated forms, while in HLM, tri‑oxygenated and demethylated products were also found. Furthermore, in vivo excretion study in rat urine samples confirmed the presence of oxygenated metabolites detected in the in vitro samples. Consequently, the study suggests that oxygenated metabolites of BEA could serve as useful biomarkers for conducting future biomonitoring studies.
期刊介绍:
Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.