The application of renal cells in culture in studying drug-induced nephrotoxicity.
Kidney cells in culture represent one of many in vitro approaches for studying drug-induced nephrotoxicity. Potential advantages of cell culture systems compared to more traditional in vitro models include a) the ability to examine direct effects at the cellular level, b) extended viability, c) ability for long-term storage, and d) capabilities for automation. Primary cultures of kidney tubules as well as cell lines of kidney origin are currently under evaluation as model systems for the assessment of nephrotoxicity. The application of two renal cell systems, rabbit primary proximal tubule cultures and the pig kidney cell line, LLC-PK1, in studying mechanisms of drug-induced nephrotoxicity is described in this communication. Potentially valuable insights into the renal pathogenesis associated with the antitumor agent, cis-diamminedichloroplatinum II, and the aminoglycoside antibiotic, gentamicin, have been obtained utilizing these renal cell models. Challenges in renal cell culture involve the characterization and maintenance of differentiated properties and the development of technologies to a) study bidirectional transport-toxicity of drugs, and b) provide a dynamic vs. static fluid environment as in vivo. Despite these unique challenges as well as the universal challenges involved in extrapolating any in vitro data to the in vivo situation, recent studies indicate that renal cells in culture are useful in the elucidation of mechanisms of drug-induced renal injury.
Williams
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PD
Biochemical Toxicology Department, Lilly Research Laboratory, Eli Lilly and Company, Greenfield, Indiana 46140.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005839:Gentamicins / Q000627:therapeutic use / Q000633:toxicity*; D006706:Homeostasis; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011817:Rabbits; D013552:Swine
D005839:Gentamicins; D002945:Cisplatin; D002118:Calcium