Background And Objective: In vitro glucuronidation of 17β-estradiol (estradiol) is often performed to assess the role of uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1) in xenobiotic/drug metabolism. The objective of this study was to determine the effects of four commonly used organic solvents [i.e., dimethyl sulfoxide (DMSO), methanol, ethanol, and acetonitrile] on the glucuronidation kinetics of estradiol, which can be glucuronidated at C3 and C17 positions.
Methods: The impacts of organic solvents on estradiol glucuronidation were determined by using expressed UGT enzymes and liver microsomes from both human and animals.
Results: In human liver microsomes (HLM), methanol, ethanol, and acetonitrile significantly altered estradiol glucuronidation kinetics with increased V (up to 2.6-fold) and CL (up to 2.8-fold) values. Altered estradiol glucuronidation in HLM was deduced to be attributed to the enhanced metabolic activities of UGT1A1 and UGT2B7, whose activities differ at the two glucuronidation positions. The effects of organic solvents on estradiol glucuronidation were glucuronidation position-, isozyme-, and solvent-specific. Furthermore, both ethanol and acetonitrile have a greater tendency to modify the glucuronidation activity of estradiol in animal liver microsomes.
Conclusion: Organic solvents such as methanol, ethanol, and acetonitrile showed great potential in adjusting the glucuronidation of estradiol. DMSO is the most suitable solvent due to its minimal influence on estradiol glucuronidation. Researchers should be cautious in selecting appropriate solvents to get accurate results when assessing the metabolism of a new chemical entity.
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http://dx.doi.org/10.1007/s13318-024-00888-2 | DOI Listing |
Sci Rep
December 2024
University of São Francisco, São Francisco de Assis av, 218, Taboão, Bragança Paulista, São Paulo, 12900-000, Brazil.
The effectiveness of indirect Intravascular laser irradiation of blood (ILIB) is not fully understood. In this study, we provided a novel experiment that employs metabolomics to investigate the effects of ILIB in women. Twenty-eight volunteers underwent indirect ILIB and had their plasma collected before and after this procedure.
View Article and Find Full Text PDFEnviron Int
November 2024
Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China. Electronic address:
Transplanting young feces into the aged was found to effectively counteract the endocrine disrupting effects of perfluorobutanesulfonate (PFBS) pollutant, showing promise in the maintenance of healthy aging. However, the interactive mechanisms between young fecal transplantation and PFBS endocrine disruption during aging remain unclear. In this follow-up study, aged zebrafish were administered young donor feces and then exposed to environmentally relevant concentrations of PFBS (0 and 100 μg/L).
View Article and Find Full Text PDFFront Pharmacol
September 2024
Anhui Province Key Laboratory of Research, Development of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, China.
Introduction: is a traditional Chinese medicine (TCM) that tonifies the kidneys and prevents miscarriage. According to Chinese medicine theory, kidney deficiency is one of the main causes of recurrent spontaneous abortion (RSA). The previous studies showed that raw product of (SP) and processed with salt solution (YP) have ameliorative effects on RSA, and that YP is superior to SP.
View Article and Find Full Text PDFDrug Metab Dispos
November 2024
Department of Physiology (B.D.W., Y.M., A.R.O., M.B., D.P.S., E.M.L.), Membrane Protein Disease Research Group (B.D.W., Y.M., M.B., D.P.S., E.M.L.), and Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology (X.C.L., E.M.L.), University of Alberta, Edmonton, Alberta, Canada; Department of Pathology and Molecular Medicine, Division of Cancer Biology and Genetics, Sinclair Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (G.C., S.P.C.C.); Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut (Z.P.L.); and Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee (Y.W., J.D.S.)
Millions of people globally are exposed to the proven human carcinogen arsenic at unacceptable levels in drinking water. In contrast, arsenic is a poor rodent carcinogen, requiring >100-fold higher doses for tumor induction, which may be explained by toxicokinetic differences between humans and mice. The human ATP-binding cassette subfamily C (ABCC) transporter hABCC4 mediates the cellular efflux of a diverse array of metabolites, including the glutathione (GSH) conjugate of the highly toxic monomethylarsonous acid (MMA), monomethylarsenic diglutathione [MMA(GS)], and the major human urinary arsenic metabolite dimethylarsinic acid (DMA).
View Article and Find Full Text PDFBMC Cancer
September 2024
Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, Jiangxi Medical Center for Critical Public Health Events, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330052, Jiangxi, P.R. China.
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