PMID: 9438665Jan 23, 1998Paper

Tubular toxicity of cyclosporine A and the influence of endothelin-1 in renal cell culture models (LLC-PK1 and MDCK)

Pediatric Nephrology : Journal of the International Pediatric Nephrology Association
L B ZimmerhacklM Brandis

Abstract

To evaluate the effect of cyclosporine A (CyA) at high concentrations (10(-4) and 10(-5) M) and the influence of endothelin-1 (ET-1) at physiological and pharmacological concentrations (10(-14) to 10(-6) M) on epithelial cell function, LLC-PK1 cells were studied as a model of the proximal tubule and MDCK cells as a model of the distal tubule/collecting duct. CyA caused time- and concentration-dependent acute toxicity. In LLC-PK1 cells, CyA caused a decrease in transepithelial resistance, indicating a loss of cell contacts, a release of lactate dehydrogenase (LDH) and villin into the supernatant, suggesting destruction of the apical membrane with loss of brush border, and finally release of uvomorulin, suggesting a disruption of the cell-cell adhesion, the zonula adherens. DNA synthesis, as evaluated by bromodeoxyuridine (BrdU) incorporation, was significantly affected at > or = 10(-5) M CyA. The toxicity of CyA was higher when given from the apical rather than the basolateral compartment. ET-1 alone was without effect, but in combination with CyA, ET-1 significantly enhanced toxicity. The ET-1 effect was partially inhibitable by an ET(B), but not an ET(A), antagonist. Immunofluorescence for alpha-catenin, another protein of the...Continue Reading

Citations

Apr 15, 2003·Journal of the American College of Surgeons·Chumpon WilasrusmeeDilip S Kittur
Dec 18, 2001·Journal of Pharmaceutical Sciences·K D Peteherych, K M Wasan
Jan 19, 2012·Pharmacology & Therapeutics·Anna AstashkinaDavid W Grainger
Feb 24, 2007·Pharmacology & Therapeutics·Walter C Prozialeck, Joshua R Edwards
Apr 11, 2003·Journal of Pharmacological Sciences·Masashi NishidaKenji Hamaoka
Apr 7, 2017·American Journal of Physiology. Cell Physiology·Allen J YiuBidhan C Bandyopadhyay
Jul 16, 2004·Journal of Cellular Physiology·Ming-Ju WuYeong-Hau H Lien
Apr 16, 2003·Hypertension·Michael VetterChung-Ho Chang
Mar 17, 2007·Renal Failure·Andrezza Sanches GarofaloOscar Fernando Pavão dos Santos
Aug 5, 1998·The American Journal of Physiology·L B ZimmerhacklM Brandis
Jan 8, 2010·American Journal of Physiology. Renal Physiology·Istvan AranyYoshikuni Nagamine

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