Renal transport and disposition of Na-2-mercaptoethane sulfonate disulfide (dimesna) in the rat.
The transport and reduction of dimesna (Na-2-mercaptoethane sulfonate disulfide) was studied in vitro using isolated, perfused rat kidney, and isolated renal epithelial cells. Cellular uptake of dimesna was found to be dependent on an active transport mechanism working across the luminal brush border, with an app. Km of approximately 22 microM and Vmax approximately 1.4 nmol . 10(6) cells-1 . min-1. Among other low molecular thiols or disulfides reduced glutathione was the only one to exert competitive inhibition. gamma-GT-activity or cellular GSH status had no influence on renal uptake of dimesna, but the intracellular reduction rate was dependent on access to reduced glutathione as a cofactor.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008623:Mercaptoethanol / Q000031:analogs & derivatives*; D015080:Mesna / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D013438:Sulfhydryl Compounds; D008623:Mercaptoethanol; C027032:2,2'-dithiodiethanesulfonic acid; D005978:Glutathione; D015080:Mesna