Detoxification mechanism in the rat extraorbital lacrimal gland: conjugation of brefeldin A to glutathione.
In this work the existence of a glutathione based detoxification system in rat lacrimal glands is reported. We showed that brefeldin A, a drug used as a tool for the study of intracellular trafficking mechanisms, was inactivated by metabolization and converted into two derivatives. We purified them by high performance liquid chromatography and determined, by mass spectroscopy, that they correspond to glutathione and cysteine derivatives of BFA. The determination of the respective amounts of these derivatives in the medium and the tissue in different experimental conditions, revealed that glutathione-BFA is formed in the tissue, excreted from the cells, cleaved by gamma-glutamyl transpeptidase and finally converted to cysteine-BFA.
Robin
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Laboratoire de Biochimie des Transports Cellulaires, CNRS URA 1116, Université Paris XI, Orsay, France.
Rossignol
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B
Raymond
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MN
D000818:Animals; D020126:Brefeldin A; D002851:Chromatography, High Pressure Liquid; D003517:Cyclopentanes / Q000493:pharmacokinetics*; D003545:Cysteine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D008658:Inactivation, Metabolic / Q000502:physiology; D007555:Isoxazoles / Q000494:pharmacology; D007765:Lacrimal Apparatus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D020126:Brefeldin A; D005978:Glutathione; D003545:Cysteine; C006303:acivicin