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AIDS. 2017 Jul 31;31(12):1679-1684. doi: 10.1097/QAD.0000000000001572.

Tenofovir-induced toxicity in renal proximal tubular epithelial cells: involvement of mitochondria.

Author information

1
aDepartment of Pharmacology, Faculty of Medicine, University of Valencia bFISABIO cDepartment of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia dServicio de Nefrología, Hospital Universitario Doctor Peset eDepartment of Nephrology, Hospital Clinico-University of Valencia fCIBERehd, Valencia, Spain.

Abstract

OBJECTIVE:

In-vivo studies suggest that mitochondria is involved in tenofovir (TFV)-induced renal toxicity, but the underlying mechanisms are still unclear. The aim of the present study was to assess the effects of TFV and its prodrug, TFV disoproxil fumarate, on mitochondrial function and cell survival/viability in a renal proximal tubular cell line.

DESIGN AND METHODS:

We evaluated parameters of cellular proliferation/survival (cell count, cell cycle, viability) and mitochondrial function (oxygen consumption, mitochondrial membrane potential, reactive oxygen species production) in NRK-52E cells. Intracellular TFV was measured by HPLC and expression of antioxidant genes was analysed by real-time PCR.

RESULTS:

Similar intracellular levels of TFV were reached with lower concentrations of the prodrug than of the drug, and correlated directly with a decrease in cell number. Both compounds inhibited proliferation and compromised mitochondrial function by decreasing mitochondrial membrane potential and increasing oxygen consumption and mitochondrial superoxide production. Altered oxidative status was confirmed by the overexpression of antioxidant genes.

CONCLUSIONS:

Intracellular accumulation of TFV induces mitochondrial toxicity in an in-vitro renal model and alters cell proliferation and viability. Our findings call for caution regarding the use of this nucleotide analogue reverse transcriptase inhibitor in patients with other risk factors that compromise mitochondrial function in the kidney.

PMID:
28650379
DOI:
10.1097/QAD.0000000000001572
[Indexed for MEDLINE]

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