In vitro phase I metabolism of vinclozolin by human liver microsomes

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Marycarmen Cruz-HurtadoAdolfo Sierra-Santoyo

Abstract

1. Vinclozolin (Vin) is a fungicide used in agricultural settings and is classified as an endocrine disruptor. Vin is non-enzymatically hydrolyzed to 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1) and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2) metabolites. There is no information about Vin biotransformation in humans, therefore, the aim of this study was to characterize its in vitro metabolism using human liver microsomes. 2. Vin was metabolized to the [3-(3,5-dichlorophenyl)-5-methyl-5-(1,2-dihydroxyethyl)-1,3-oxazolidine-2,4-dione] (M4) and N-(2,3,4-trihydroxy-2-methyl-1-oxo)-3,5-dichlorophenyl-1-carbamic acid (M7) metabolites, which are unstable and gradually converted to 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutyranilide (DTMBA, formerly denoted as M5). M4 and DTMBA metabolites co-eluted in the same HPLC peak; this co-elute peak exhibited a Michaelis-Menten kinetic, whereas M7 showed a substrate inhibition kinetics. The KM app for co-eluted M4/DTMBA and M7 was 24.2 ± 5.6 and 116.0 ± 52.6 μM, the VMax app was 0.280 ± 0.015 and 0.180 ± 0.060 nmoles/min/mg protein, and the CLint app was 11.5 and 1.5 mL/min/g protein, respectively. The Ki for M7 was 133.2 ± 63.9 μM. Cytochrome P450 (CYP) chem...Continue Reading

References

Apr 1, 1995·Occupational and Environmental Medicine·A ZoberB van Ravenzwaay
Oct 9, 1998·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·D McKillopC Simcock
May 2, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·C J WolfL E Gray
Jun 8, 2001·Journal of Chromatography. B, Biomedical Sciences and Applications·K WittkeJ Begerow
Nov 8, 2001·Journal of Clinical Pharmacology·K VenkatakrishnanD J Greenblatt
Oct 12, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Tobias Weiss, Jürgen Angerer
Jan 8, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·David M StresserCharles L Crespi
Jul 30, 2004·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Adolfo Sierra-SantoyoMichael F Hughes
Apr 6, 2006·Reproduction : the Official Journal of the Society for the Study of Fertility·D N R VeeramachaneniK-Y F Pau
Jun 6, 2006·Toxicology and Applied Pharmacology·José-Manuel Molina-MolinaPatrick Balaguer
Jun 5, 2008·Journal of Agricultural and Food Chemistry·Julian BursztykaJean-Pierre Cravedi
Aug 16, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Adolfo Sierra-SantoyoMichael F Hughes
Sep 16, 2008·International Journal of Hygiene and Environmental Health·Birgitta KüttingHans Drexler
Feb 22, 2011·European Journal of Drug Metabolism and Pharmacokinetics·Siamak Cyrus KhojastehAnthony Y H Lu
Oct 4, 2011·Drug Metabolism Reviews·Baojian Wu
Oct 18, 2011·Archives of Toxicology·Adolfo Sierra-SantoyoMichael F Hughes
Jul 17, 2012·Environment International·Erin L WickerhamJohn D Meeker
Dec 23, 2014·Reproduction in Domestic Animals = Zuchthygiene·Y HuangK S Wu
Mar 13, 2018·Toxicology and Applied Pharmacology·Marycarmen Cruz-HurtadoAdolfo Sierra-Santoyo

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Jun 3, 2021·International Journal of Molecular Sciences·Raquel CanoValmore Bermúdez

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