ADVANTAGES OF A 2-CHAMBER CULTURE SYSTEM TO TEST DRUG NEPHROTOXICITY - THE EXAMPLE OF CEPHALORIDINE

Rabbit renal proximal tubular cells, cultured to confluency on a perme able collagen film in a two-chamber system, were exposed for 72 h to v arious concentrations of the nephrotoxic antibiotic, cephaloridine (CL D). A decrease in cellular proteins, leakage of lactate dehydrogenase and morphological changes appeared at CLD concentrations of 0.1, 1.0, and 0.5 mg/ml, respectively. The permeability of the monolayer to Luci fer yellow (LY), a dye that does not cross cell membranes, was increas ed by 1 or 2 mg/ml but not by lower concentrations of CLD. The large b asolateral/apical glucose concentration gradient established by the ce lls was decreased by CLD. However, the fact that, at the CLD concentra tion of I mg/ml, LY totally equilibrated by diffusion across the monol ayer, whereas the injured monolayer was still able to maintain a detec table glucose gradient, shows that damage caused by CLD to the diffusi on barrier prevails over that affecting glucose uptake. Consistent wit h the data in the literature concerning the mechanism of CLD accumulat ion in renal cells, our results show that CLD was more toxic when it w as added at the basolateral than at the apical side of the cultured ce lls. These results illustrate the advantages of using a two-chamber sy stem of cell culture in nephrotoxicity studies.