Renal proximal tubule cell cultures for studying drug-induced nephrotoxicity and modulation of phenotype expression by medium components

Abstract

The characteristics of two established renal cell lines (LLC-PKI and OK) and of primary cultures of rabbit and human proximal tubule cells are described by summarizing the literature about specific properties retained by these cells in culture. Furthermore, comparative biochemical and functional properties are presented including both specific marker enzymes and transport properties of these cells grown in various media. The impact of culture medium composition on the expressed cellular phenotype is discussed and its consequences on the profile of toxic response due to aminoglycoside antibiotics is analyzed. The in vitro nephrotoxicity of three platinum-containing coordination complexes which exhibited different in vivo nephrotoxic potentials is studied by another technique in a model of rabbit proximal tubule cells in primary cultures in order to correlate results to in vivo data and to define reliable and sensitive parameters for the assessment of platinum-derivative-induced nephrotoxicity. Although animal cell lines have been established in serum-supplemented medium, LLC-PK1 and OK cells as well as primary cultures of proximal tubules are successfully grown in hormonally defined medium, the standardization of which is better controlled for nephrotoxicity studies.