Rachel Murphy

  • Mar 17, 2017
  • Seminars
Topic: “Tenofovir Induced Nephrotoxicity:
A Mechanistic Study"
Date: Wednesday, May 17, 2017
Time: 9:30am
Place: B448 Life Science Bldg 

 

Tenofovir (TFV) is a reverse transcriptase inhibitor that is FDA approved
to treat HIV and chronic Hepatitis B. It has a long half-life, allowing for
once a day dosing and is effective in both treatment novel and treatment
experienced patients. It is administered orally as tenofovir disoproxil
fumarate (TDF) and is deesterified in the intestine to the active drug
TFV. However, renal impairment is associated with its use; TFV can induce
decreased glomerular filtration rate (GFR) and free calcitriol, renal failure,
and Fanconi Syndrome. The exact mechanism of toxicity currently remains
unknown, largely due to limited experimental models. Our laboratory
has established that clinically relevant concentrations of TFV are toxic
within 24 h in an immortalized human proximal tubule cell line (HK-2). The
purpose of this study was to investigate the mechanisms of cytotoxicity
and oxidative damage observed in HK-2 cells following treatment with TFV
and to determine if managing oxidative damage mitigates toxicity. TFV is
the active form of TDF and was used for all studies. HK-2 cells were grown
to confluency for 48 h and then exposed to 0-28.8uM TFV for 24, 48, or
72 h. The vehicle used for all studies was phosphate buffered saline (PBS).