LC-MSMS characterisations of scymnol and oxoscymnol biotransformations in incubation mixtures of rat liver microsomes
| Autor: | Nicolette Kalafatis, Paul F.A. Wright, Linda L. Glowacki, Theodore A. Macrides, Lynn D. Hodges, Paul Wynne |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_treatment Biochemistry Steroid Rats Sprague-Dawley Hydroxylation 03 medical and health sciences chemistry.chemical_compound Nutraceutical Biotransformation Tandem Mass Spectrometry medicine Animals Incubation 030102 biochemistry & molecular biology General Medicine Metabolism Ketosteroids Rats 030104 developmental biology chemistry Steroid Hydroxylases Microsomes Liver Microsome Xenobiotic Cholestanols Chromatography Liquid |
| Zdroj: | Biochimie. 160:130-140 |
| ISSN: | 0300-9084 |
| DOI: | 10.1016/j.biochi.2019.02.016 |
| Popis: | The bile alcohol 5β-scymnol ([24R]-(+)-5β-cholestan-3α,7α,12α,24,26,27-hexol) is a therapeutic nutraceutical derived from marine sources, however very little is known about its potential for biotransformation as a xenobiotic in higher vertebrates. In this study, biotransformation products of scymnol catalysed by liver microsomes isolated from normal and streptozotocin (STZ)-treated male Wistar rats were characterised by liquid chromatography-tandem mass spectroscopy (LC-MSMS). In order of increasing polarity relative to the reversed phase sorbent, structural assignments were made for four biotransformation products, namely 3-oxoscymnol (5β-cholestan-3-one-7α,12α,24,26,27-pentol); 7-oxoscymnol (5β-cholestan-7-one-3α,12α,24,26,27-pentol); 3β-scymnol (5β-cholestan-3β,7α,12α,24,26,27-hexol) and 6β-hydroxyscymnol (5β-cholestan-3α,6β,7α,12α,24,26,27-heptol). In addition, a total of eight biotransformation products were characterised from microsomal incubations of crude oxoscymnol compounds, namely 7β-scymnol; 3,12-dioxoscymnol; 3,7-dioxoscymnol; 7,12-dioxoscymnol; 12-oxo-3β-scymnol; 7-oxo-3β-scymnol; 6β-hydroxy-12-oxoscymnol and 6β-hydroxy-7-oxoscymnol. Collectively, the results indicate hepatic enzyme-catalysed hydroxylation, dehydrogenation and epimerisation reactions on the steroid nucleus of scymnol, and provide an insight into biotransformation pathways for scymnol use as a therapeutic nutraceutical in higher vertebrates. |
| Databáze: | OpenAIRE |
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