Cytotoxic Effects of FK506 on Human Renal Proximal Tubule Cells in Culture

FK506 has been used as the primary immunosuppressive agent administered after a variety of organ transplants, with less reported nephrotoxicity than that of cyclosporine. This study examined in vitro cytotoxicity of FK506 on normal human renal proximal tubule cells. Cytotoxicity was assessed by neut...

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Bibliographic Details
Published in:In vitro cellular & developmental biology. Animal 1994-09, Vol.30A (9), p.562-567
Main Authors: Atcherson, M M, Trifillis, A L
Format: Article
Language:English
Subjects:
Cell Survival - drug effects
Cells, Cultured
Cellular and Molecular Toxicology
Cultured cells
Cyclosporins
Dose-Response Relationship, Drug
Hepatocytes
Humans
Immunosuppressants
Kidney cells
Kidney Tubules, Proximal - drug effects
Kidney Tubules, Proximal - ultrastructure
Microscopy, Electron
Microscopy, Phase-Contrast
Nephrons
Nephrotoxicity
Neutral Red
Proximal tubules
Staining and Labeling
Tacrolimus - administration & dosage
Tacrolimus - pharmacology
Tacrolimus - toxicity
Trypan Blue
Vacuoles - drug effects
Vehicles
Viability
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Summary:FK506 has been used as the primary immunosuppressive agent administered after a variety of organ transplants, with less reported nephrotoxicity than that of cyclosporine. This study examined in vitro cytotoxicity of FK506 on normal human renal proximal tubule cells. Cytotoxicity was assessed by neutral red inclusion and trypan blue exclusion; morphology was assessed by light and transmission electron microscopy. Neutral red inclusion decreased to less than 10% of the control after 3 days exposure to 200 (µg/ml FK506. Forty microgram per milliliter FK506 caused a decrease in neutral red inclusion to 61% of the control on Day 7, with recovery to 86% on Day 12. Similarly, trypan blue exclusion decreased to 66% of the control following 7 days exposure to 40 µg/ml FK506, and confluency of the monolayer was reduced to 50% as evidenced by phase contrast microscopy. After a 12-day exposure, treated monolayers became more confluent. On ultrastructural examination, FK506-treated cells exhibited increased cytoplasmic vacuolation and lipid inclusion. These data suggest that FK506 is reversibly and mildly toxic to monolayers of human renal proximal tubule cells and are consistent with clinical reports of reversible nephrotoxicity.
ISSN:1071-2690
1543-706X
DOI:10.1007/BF02631253