The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Assessment of Mitochondrial Toxicity in Human Cells Treated with Tenofovir: Comparison with Other Nucleoside Reverse Transcriptase Inhibitors
Open accessAbstract
Drug-associated dysfunction of mitochondria is believed to play a role in the etiology of the various adverse symptoms that occur in human immunodeficiency virus (HIV)-infected patients treated with the nucleoside reverse transcriptase inhibitors (NRTIs). Tenofovir, a nucleotide analog recently approved for use in the treatment of HIV infection, was evaluated in vitro for its potential to cause mitochondrial toxicity and was compared to currently used NRTIs. Treatment with tenofovir (3 to 300 μM) for up to 3 weeks produced no significant changes in mitochondrial DNA (mtDNA) levels in human hepatoblastoma (HepG2) cells, skeletal muscle cells (SkMCs), or renal proximal tubule epithelial cells. The potencies of inhibition of mtDNA synthesis by the NRTIs tested were zalcitabine (ddC) > didanosine (ddI) > stavudine > zidovudine (ZDV) > lamivudine = abacavir = tenofovir, with comparable relative effects in the three cell types. Unlike ddC and ddI, tenofovir did not affect cellular expression of COX II and COX IV, two components of the mitochondrial cytochrome c oxidase complex. Lactate production was elevated by less than 20% in HepG2 cells or SkMCs following treatment with 300 μM tenofovir. In contrast, lactate synthesis increased by >200% in the presence of 300 μM ZDV. Thus, treatment of various human cell types with tenofovir at concentrations that greatly exceed those required for it both to have in vitro anti-HIV type 1 activity in peripheral blood mononuclear cells (50% effective concentration, 0.2 μM) and to achieve therapeutically relevant levels in plasma (maximum concentrations in plasma, 0.8 to 1.3 μM) is not associated with mitochondrial toxicity.
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Cites
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Cited by
De Clercq, E. (2003) · Clinical Microbiology Reviews · doi:10.1128/cmr.16.4.569-596.2003 · Cited by 369
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Renal Tubular Dysfunction Associated With Tenofovir Therapy: Report of 7 Cases
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Ageing with HIV: Challenges and biomarkers
Rodés, B., Cadiñanos, J., Esteban-Cantos, A., Rodríguez-Centeno, J., & Arribas, J. R. (2022) · eBioMedicine · doi:10.1016/j.ebiom.2022.103896 · Cited by 136
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Metadata
- Authors
- Birkus, G., Hitchcock, M. J. M., & Cihlar, T.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2002-03
- Volume
- 46
- Issue
- 3
- Pages
- 716-723
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- OpenAlex
- W2126327126
- Cited by
- 441
- References
- 35
- FWCI
- 22.43
- Type
- journal article
- Language
- en
- Open access
- green
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