Format

Send to

Choose Destination
See comment in PubMed Commons below
J Acquir Immune Defic Syndr. 2009 Jul 1;51(3):258-63.

Mitochondrial tubulopathy in tenofovir disoproxil fumarate-treated rats.

Author information

1
Department of Rheumatology, University Hospital, Freiburg, Germany.

Abstract

OBJECTIVES:

Tenofovir disoproxil fumarate (tenofovir DF) use has been associated with renal dysfunction and Fanconi syndrome. Tenofovir is taken up into renal tubules by anion transporters where high intracellular drug concentration may induce a functionally relevant depletion of mitochondrial DNA (mtDNA). We investigated if tenofovir may induce renal mtDNA depletion and respiratory chain dysfunction.

METHODS:

Rats (n = 8) were gavaged daily with 100 mg x kg(-1) x d(-1) of tenofovir DF or didanosine. Kidneys and livers were examined after 8 weeks of treatment.

RESULTS:

The tenofovir group had significantly lower body and kidney weights than rats exposed to water or didanosine. Proximal but not distal tubules were of increased diameter and contained small lipid droplets. Tubular mitochondria were enlarged, and their crystal architecture was disrupted. Tenofovir-exposed kidneys contained low mtDNA copy numbers and impaired expression of mtDNA-encoded cytochrome c oxidase (COX) I but not nucleus-encoded COX IV subunits. Histochemistry demonstrated low tubular COX and nicotinamide adenine dinucleotide dehydrogenase (NADH-DH) activities, whereas succinate dehydrogenase activity was preserved. COX activity was preserved in the glomeruli of tenofovir-exposed rats. Didanosine did not elicit renal effects but, unlike tenofovir, depleted mtDNA in liver (by 52%).

CONCLUSIONS:

Tenofovir DF induces an organ-specific nephrotoxicity with mtDNA depletion and dysfunction of mtDNA-encoded respiratory chain subunits. The data do not support nephrotoxicity of didanosine.

PMID:
19582894
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Lippincott Williams & Wilkins
    Loading ...
    Support Center