Freshly isolated primary human proximal tubule cells as an in vitro model for the detection of renal tubular toxicity

Toxicology ◽  
2020 ◽  
Vol 442 ◽  
pp. 152535 ◽  
Author(s):  
Piyush Bajaj ◽  
Git Chung ◽  
Keith Pye ◽  
Tomoya Yukawa ◽  
Akio Imanishi ◽  
...  
2007 ◽  
Vol 107 (2) ◽  
pp. e47-e56 ◽  
Author(s):  
Natalie Glube ◽  
Andreas Giessl ◽  
Uwe Wolfrum ◽  
Peter Langguth

2002 ◽  
Vol 282 (4) ◽  
pp. F703-F709 ◽  
Author(s):  
Richard A. Girton ◽  
David P. Sundin ◽  
Mark E. Rosenberg

Clusterin is a heterodimeric secreted glycoprotein that is upregulated after acute renal injury. In aminoglycoside nephrotoxicity, clusterin is induced in the tubular epithelium and increased levels are found in the urine. In this study, we developed an in vitro model of gentamicin-induced cytotoxicity in renal proximal tubule cells and tested whether clusterin protected these cells from injury. LLC-PK1 cells were incubated with varying concentrations of gentamicin in serum-free media, and cytotoxicity was quantified by lactate dehydrogenase release and confirmed by vital dye exclusion. A dose-dependent increase in cytotoxicity occurred with gentamicin concentrations up to 27 mg/ml. Clusterin decreased cytotoxicity in a dose- and time-dependent manner at 6, 12, and 24 h, whereas albumin, used as a control protein, had no effect. In contrast to the aminoglycoside model, when cells were injured by depletion of ATP, clusterin had only a minimally protective effect. LLC-PK1 cells did not express megalin, a receptor that can mediate the uptake of both clusterin and aminoglycosides into proximal tubule cells. Uptake of gentamicin into LLC-PK1cells was observed despite the absence of megalin. In conclusion, clusterin specifically protects against gentamicin-induced renal tubular cell injury by a megalin-independent mechanism.


2014 ◽  
Vol 119 (3) ◽  
pp. 570-577 ◽  
Author(s):  
Raphael R. Bruno ◽  
Winfried Neuhaus ◽  
Norbert Roewer ◽  
Christian Wunder ◽  
Martin A. Schick

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii407-iii407
Author(s):  
Noel Knops ◽  
Yasaman Ramazani ◽  
Bert van den Heuvel ◽  
Elena Levtchenko ◽  
Dirk Kuypers

2017 ◽  
Vol 4 ◽  
pp. 342-347 ◽  
Author(s):  
Miriam E. Mossoba ◽  
Sanah Vohra ◽  
Howard Toomer ◽  
Shelia Pugh-Bishop ◽  
Zachary Keltner ◽  
...  

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