Possible Interaction: Dicumarol and Glutathione

“ Dicoumarol induced a marked decrease in cellular redox of glutathione in KKU-100 cells, in contrast to KKU-M214 cells.”

“However, unexpectedly dicoumarol inhibited the cellular multidrug resistance protein (Mrp) 1-dependent export of GSH in a time- and concentration-dependent manner with half-maximal effects observed at low micromolar concentrations of dicoumarol.”

“In addition, dicoumarol inhibited also the Mrp1-mediated export of GSSG during menadione-induced oxidative stress and the export of the GSH –bimane-conjugate (GS–B) that had been generated in the cells after exposure to monochlorobimane.”

“These data demonstrate that dicoumarol strongly affects the GSH metabolism of viable cultured astrocytes by inhibiting Mrp1-mediated export processes and identifies for the first time Mrp1 as additional cellular target of dicoumarol.”

“Catalase, competitive scavengers and GSH inhibited .OH production, as did dicoumarol.”

“ Dicumarol … GSH peroxidase II activity, inhibiting the reduction of cumene hydroperoxide by GT-10.6, the predominant class alpha GSH transferase of mouse liver, with an … microM. GSH peroxidase I (EC 1.11.1.9) and GSH peroxidase II activities were resolved by chromatography of liver and testis cytosols.”

“ Dicumarol , often used as a specific inhibitor of DT diaphorase (NAD(P)H:(quinone-acceptor) oxidoreductase; EC 1.6.99.2), was found to potently inhibit GSH transferases (EC 2.5.1.18).”

“While inhibiting GSH peroxidase II with IC50 of 9-10 microM, dicumarol did not affect the activity … several other non-substrate ligands were more potent inhibitors of 1-chloro-2,4-dinitrobenzene conjugation, dicumarol … GSH transferase and GSH peroxidase II activities in … used for detection of DT diaphorase action.”

“ Dicumarol prevented the elevation of the glutathione pool caused by less than or equal to 18 microM K3.”