Details

Autor(en) / Beteiligte

• Milián, Lara
• Peris, José E
• Gandía, Patricia
• Andújar, Isabel
• Pallardó, Luis
• Górriz, Jose L
• Blas-García, Ana

Titel

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

Ist Teil von

• AIDS (London), 2017-07, Vol.31 (12), p.1679-1684

Ort / Verlag

England: Copyright Wolters Kluwer Health, Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• OBJECTIVE:In vivo studies suggest that mitochondria is involved in tenofovir-induced renal toxicity, but the underlying mechanisms are still unclear. The aim of the present study was to assess the effects of tenofovir and its prodrug, tenofovir 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 NRK52E cells. Intracellular tenofovir was measured by HPLC and expression of antioxidant genes was analysed by Real Time PCR. RESULTS:Similar intracellular levels of tenofovir 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 tenofovir 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 NRTI in patients with other risk factors that compromise mitochondrial function in the kidney.