alexa Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2.
Nephrology

Nephrology

Journal of Kidney

Author(s): Ciarimboli G, Ludwig T, Lang D, Pavenstdt H, Koepsell H,

Abstract Share this page

Abstract Cis-platin is an effective anti-neoplastic agent, but it is also highly nephrotoxic. Here, we clearly identify the human organic cation transporter 2 (hOCT2) as the critical transporter for cis-platin nephrotoxicity in isolated human proximal tubules and offer a potential mechanism for reducing nephrotoxicity in clinical practice. Interaction of cis-platin with hOCT2 in kidney or hOCT1 in liver was investigated with the fluorescent cation 4-[4-(dimethyl-amino)styril]-methylpyridinium in stably transfected HEK293 cells and for the first time in tissues physiologically expressing these transporters, human proximal tubules, and human hepatocyte couplets. Cis-platin (100 micromol/L) inhibited transport via hOCT2-HEK293 but not hOCT1-HEK293. In human proximal tubules cis-platin competed with basolateral organic cation transport, whereas it had no effect in tubules from a diabetic kidney or in hepatocytes. In hOCT2-HEK293 cells treated for 15 hours, incubation with cis-platin induced apoptosis, which was completely suppressed by contemporaneous incubation with the hOCT2 substrate cimetidine (100 micromol/L). These findings demonstrate that uptake of cis-platin is mediated by hOCT2 in renal proximal tubules, explaining its organ-specific toxicity. A combination of cis-platin with other substrates that compete for hOCT2 offers an effective option to decrease nephrotoxicity in the clinical setting.
This article was published in Am J Pathol and referenced in Journal of Kidney

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 2nd Annual Kidney Congress
    Aug 28-30, 2017, Philadelphia, USA
  • 16th European Nephrology Conference
    Oct 02-04, 2017, Barcelona, Spain
  • 16th International Conference on Nephrology
    Nov 02-03, 2017, Atlanta, USA

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords