DISPOSITION OF THE BROMOSULFOPHTHALEIN-GLUTATHIONE CONJUGATE IN THE ISOLATED-PERFUSED RAT-KIDNEY

Renal elimination of the bromosulfophthalein-glutathione conjugate (BS P-GSH) after its i.v. administration in the rat in vivo is negligible. In our study we wanted to establish whether the high albumin-binding of BSP-GSH constitutes the major restrictive factor toward the urinary excretion of the compound. The renal disposition of BSP-GSH was studi ed in the isolated rat kidney during perfusions with or without albumi n in the perfusate. The urinary clearance of BSP-GSH in the absence of albumin was very low (<60 mu l/min) as compared to the inulin clearan ce (approximately 300 mu l/min). This indicates that albumin-binding i s not the major reason for the low urinary clearance of BSP-GSH. Addit ion of albumin to the perfusate further decreased the urinary excretio n by 60%. BSP-GSH is metabolized by the kidney into two major metaboli tes: the cysteinylglycine conjugate and the di-glutathione conjugate. Both metabolites appear in perfusate, which suggests that BSP-GSH unde rgoes tubular (re-)uptake. The di-glutathione conjugate is further met abolized to the di-cysteinylglycine conjugate. The di-glutathione conj ugate and the di-cysteinylglycine conjugate are the major urinary comp onents and the urinary elimination of BSP-GSH may depend on their form ation. Inhibition of gamma-glutamyl transpeptidase activity with acivi cin largely prevented the degradation to the cysteinylglycine and dicy steinylglycine conjugates of BSP. The total rate of urinary excretion, however, was only slightly lowered by acivicin. Apparently, cleavage of the gamma-glutamyl moiety is not relevant for the total urinary eli mination of BSP-GSH.