Interactions of the antitumor drug, etoposide, with reduced thiols in vitro and in vivo. Chem Biol Interact 1987;62(3):237-47
Date
01/01/1987Pubmed ID
3040275DOI
10.1016/0009-2797(87)90025-1Scopus ID
2-s2.0-0023266733 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
The interaction of activated etoposide, 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyra noside) (VP-16), with thiols has been studied both in vitro and in vivo in mice. We have found that both glutathione (GSH) and cysteine rapidly reduce the VP-16 free radical, which results in the regeneration of the parent drug and the oxidation of the thiol. Using spin-trapping and electron spin resonance (ESR) techniques, we have shown that this one-electron/hydrogen donation by thiols forms thiyl radicals (RS.) which are intermediates for the formation of the oxidized thiols. The administration of VP-16 in vivo to mice decreased the total thiol levels in liver and concomitantly increased the formation of oxidized thiols. Furthermore, VP-16 stimulated glutathione reductase in liver. While administration of VP-16 also increased the total thiol pools in kidney, in contrast, no significant effects were observed on lung and heart thiol pools.
Author List
Katki AG, Kalyanaraman B, Sinha BKAuthor
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCyclic N-Oxides
Cysteine
Electron Spin Resonance Spectroscopy
Etoposide
Free Radicals
Glutathione
Kidney
Liver
Male
Mice
Oxidation-Reduction
Sulfhydryl Compounds