Oxidative metabolism of spironolactone: evidence for the involvement of electrophilic thiosteroid species in drug-mediated destruction of rat hepatic cytochrome P450

In a preliminary paper [Decker et al. (1986) Biochem. Biophys. Res. Commun. 136, 1162] we have shown that the antimineralocorticoid spironolactone (SPL) preferentially inactivates dexamethasone (DEX) inducible rat hepatic cytochrome P450p isozymes in a suicidal manner. These findings are now confirm...

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Veröffentlicht in:	Biochemistry (Easton) 1989-06, Vol.28 (12), p.5128-5136
Hauptverfasser:	DECKER, C. J, RASHED, M. S, BAILLIE, T. A, MALTBY, D, CORREIA, M. A
Format:	Artikel
Sprache:	eng
Schlagworte:	550201 - Biochemistry- Tracer Techniques ADRENAL HORMONES ANIMALS BASIC BIOLOGICAL SCIENCES Binding Sites Biological and medical sciences BODY CARBON 14 COMPOUNDS CELL CONSTITUENTS Cell metabolism, cell oxidation Cell physiology CHEMICAL REACTIONS Chromatography, High Pressure Liquid CORTICOSTEROIDS Cytochrome P-450 Enzyme Inhibitors cytochrome p450 CYTOCHROMES Dexamethasone - pharmacology DIGESTIVE SYSTEM Enzyme Induction - drug effects ESTERS Fundamental and applied biological sciences. Psychology GLANDS HETEROCYCLIC COMPOUNDS HYDROXY COMPOUNDS INACTIVATION ISOENZYMES Isoenzymes - antagonists & inhibitors KETONES Kinetics LABELLED COMPOUNDS LACTONES LIVER Male MAMMALS Mass Spectrometry METABOLISM METABOLITES MICROSOMES Microsomes, Liver - drug effects Microsomes, Liver - enzymology Molecular and cellular biology Molecular Structure NADP - pharmacology ORGANIC COMPOUNDS ORGANIC SULFUR COMPOUNDS ORGANOIDS ORGANS OXIDATION Oxidation-Reduction PIGMENTS PREGNANES PROTEINS RATS Rats, Inbred Strains RIBOSOMES RODENTS Spectrophotometry, Ultraviolet Spironolactone - analysis Spironolactone - metabolism STEROIDS Sulfinic Acids - analysis Sulfonic Acids - analysis THIOLS VERTEBRATES
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