Next Article in Journal
The PRR11-SKA2 Bidirectional Transcription Unit Is Negatively Regulated by p53 through NF-Y in Lung Cancer Cells
Next Article in Special Issue
Genetic Variants Contributing to Colistin Cytotoxicity: Identification of TGIF1 and HOXD10 Using a Population Genomics Approach
Previous Article in Journal
The Role of the Melatoninergic System in Light-Entrained Behavior of Mice
Previous Article in Special Issue
Twist2 Is Upregulated in Early Stages of Repair Following Acute Kidney Injury
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(3), 531; doi:10.3390/ijms18030531

Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity

1
Department of Pharmacology, Physiology, and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA
2
West Virginia Wesleyan College, Buckhannon, WV 26201, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Guido R. M. M. Haenen
Received: 17 January 2017 / Revised: 24 February 2017 / Accepted: 25 February 2017 / Published: 1 March 2017
(This article belongs to the Special Issue Nephrotoxicity)
View Full-Text   |   Download PDF [5336 KB, uploaded 3 March 2017]   |  

Abstract

Tenofovir (TFV) is an antiviral drug approved for treating Human Immunodeficiency Virus (HIV) and Hepatitis B. TFV is administered orally as the prodrug tenofovir disoproxil fumarate (TDF) which then is deesterified to the active drug TFV. TFV induces nephrotoxicity characterized by renal failure and Fanconi Syndrome. The mechanism of this toxicity remains unknown due to limited experimental models. This study investigated the cellular mechanism of cytotoxicity using a human renal proximal tubular epithelial cell line (HK-2). HK-2 cells were grown for 48 h followed by 24 to 72 h exposure to 0–28.8 μM TFV or vehicle, phosphate buffered saline (PBS). MTT (MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and Trypan blue indicated that TFV diminished cell viability at 24–72 h. TFV decreased ATP levels at 72 h when compared to vehicle, reflecting mitochondrial dysfunction. TFV increased the oxidative stress biomarkers of protein carbonylation and 4-hydroxynonenol (4-HNE) adduct formation. Tumor necrosis factor alpha (TNFα) was released into the media following exposure to 14.5 and 28.8 μM TFV. Caspase 3 and 9 cleavage was induced by TFV compared to vehicle at 72 h. These studies show that HK-2 cells are a sensitive model for TFV cytotoxicity and suggest that mitochondrial stress and apoptosis occur in HK-2 cells treated with TFV. View Full-Text
Keywords: tenofovir; tenofovir disoproxil fumarate; nephrotoxicity; Fanconi Syndrome; HK-2 cells tenofovir; tenofovir disoproxil fumarate; nephrotoxicity; Fanconi Syndrome; HK-2 cells
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Murphy, R.A.; Stafford, R.M.; Petrasovits, B.A.; Boone, M.A.; Valentovic, M.A. Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity. Int. J. Mol. Sci. 2017, 18, 531.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top