NEPHROTOXICITY AND UPTAKE OF 1-BENZYL QUINOLINIUM IN PRECISION-CUT RABBIT RENAL CORTICAL SLICES

Nephrotoxicity studies have not always meshed toxicity with transport and uptake, although the two are interdependent. To begin to address t his issue, a series of model organic cations (quaternary amines) was e xamined which revealed differences in toxicity that were not explained by slight structural variations. Thus, a single model organic cation, I-benzyl quinolinium (BQ), was used to assess organic cations in rabb it renal cortical slices. Histopathological evaluation revealed that B Q produced site-specific injury in the S-3 region of the proximal tubu le. Biochemical assays (K+, qO(2) and ATP) revealed dose- and time-dep endent decreases of BQ-exposed slices over 2-12 hr. Cation transport ( uptake of tetraethylammonium) was decreased by BQ at sub-toxic doses w ithin 2 hr, although anion transport (uptake of p-aminohippurate) was not affected. Understanding the toxicity and transport of model cation s such as BQ will help to identify the mechanisms associated with orga nic cation nephrotoxicity as well as to facilitate the use of transpor t parameters to prevent toxicity or prolong drug action of cations.