POLY-L-ASPARTIC ACID PROTECTS CULTURED HUMAN PROXIMAL TUBULE CELLS AGAINST AMINOGLYCOSIDE-INDUCED ELECTROPHYSIOLOGICAL ALTERATIONS

Cultured human proximal tubule cell monolayers maintained on permeable supports were treated simultaneously with the aminoglycoside antibiot ic, gentamicin, and poly-L-aspartic acid (PAA), an inhibitor of aminog lycoside nephrotoxicity. Following 4 days of exposure, cell monolayers were placed into Ussing chambers to allow monitoring of transepitheli al electrical properties. For each of the three cell isolates examined , aminoglycoside-induced alterations in electrogenic transport, reflec ted by changes in short-circuit current (Isc), as well as alterations in paracellular properties, indicated by changes in transepithelial el ectrical resistance (R(T)), were diminished in the presence of PAA. Al terations resulting from selective basolateral exposure to gentamicin- were unchanged in the case of apically applied PAA and attenuated only when PAA acid was added basolaterally. This is the first demonstratio n of PAA inhibition of aminoglycoside-induced cellular alterations inv olving human cells. (C) 1997 Elsevier Science Ireland Ltd.