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 this issue, a series of model organic cations (quaternary amines) was examined which revealed differences in toxicity that were not explained by slight structural variations. Thus, a single model organic cation, 1-benzyl quinolinium (BQ), was used to assess organic cations in rabbit renal cortical slices. Histopathological evaluation revealed that BQ produced site-specific injury in the S(3) region of the proximal tubule. Biochemical assays (K(+), qO(2) and ATP) revealed dose- and time-dependent decreases of BQ-exposed slices over 2-12 hr. Cation transport (uptake of tetraethylammonium) was decreased by BQ at sub-toxic doses within 2 hr, although anion transport (uptake of p-aminohippurate) was not affected. Understanding the toxicity and transport of model cations such as BQ will help to identify the mechanisms associated with organic cation nephrotoxicity as well as to facilitate the use of transport parameters to prevent toxicity or prolong drug action of cations.
Sheevers
H V
HV
Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85724, USA.
Brendel
K
K
Wright
S H
SH
Nagle
R B
RB
Gandolfi
A J
AJ