Author, as appears in the article.: Vidal, F; Domingo, JC; Guallar, J; Saumoy, M; Cordobilla, B; de la Rosa, RS; Giralt, M; Alvarez, ML; López-Dupla, M; Torres, F; Villarroya, F; Cihlar, T; Domingo, P
Department: Medicina i Cirurgia
URV's Author/s: López Dupla, Jesús Miguel / Vidal Marsal, Francisco
Keywords: Therapy Reverse-transcriptase inhibitors Protease inhibitors Nucleoside Nephrotoxicity Infected patients Hiv-infected patients Hiv protease inhibitors Fatal lactic-acidosis Fanconi-syndrome Failure Experienced patients Drug-induced nephrotoxicity Disoproxil fumarate Didanosine Antiviral nucleotide analogs Anion transporter 1
Abstract: We assessed the in vitro toxicity of tenofovir (TFV) and compared it with those of zidovudine (AZT), didanosine (ddI), ritonavir (RTV), and lopinavir (LPV) alone and in combination in human renal proximal tubule epithelial cells (RPTECs). The cells were treated with various concentrations and combinations of the tested antiretrovirals for up to 22 days, and cytotoxicity was determined. In addition, we assessed the levels of mitochondrial DNA (mtDNA) and cytochrome oxidase II (COII) mRNA in RPTECs treated with reverse transcriptase inhibitors. TFV alone was not associated with significant cytotoxicity. ddI showed pronounced cytotoxicity that was greater than those of AZT (P = 0.002) and TFV (P = 0.0001). The combination of 10 mu M RTV and 40 mu M LPV significantly reduced RPTEC viability (P < 0.0001), and TFV tended to partially reduce this effect. TFV alone affected neither mtDNA nor COII mRNA levels, whereas ddI caused a profound depletion of mtDNA and a parallel reduction in COII mRNA expression. The effects of ddI, but not those of AZT, on mtDNA and COII mRNA were further enhanced in the presence of TFV, a finding consistent with the inhibition of ddI clearance by TFV. The addition of TFV to ddI or AZT appeared to slightly increase the COII mRNA/mtDNA ratio relative to that in cells treated with ddI or AZT alone. Together, these in vitro results indicate that combination with other antiretrovirals does not significantly increase the toxic potential of TFV in RPTECs.
Thematic Areas: Saúde coletiva Química Pharmacology (medical) Pharmacology & pharmacy Pharmacology Odontología Nutrição Microbiology Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Interdisciplinar Infectious diseases Farmacia Ensino Engenharias iv Engenharias iii Engenharias ii Enfermagem Educação física Educação Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências agrárias i Ciência de alimentos Biotecnología Biodiversidade Astronomia / física
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: jesusmiguel.lopez@urv.cat francesc.vidal@urv.cat
Author identifier: 0000-0002-9141-2523 0000-0002-6692-6186
Record's date: 2024-02-18
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://journals.asm.org/doi/10.1128/aac.00437-06
Papper original source: Antimicrobial Agents And Chemotherapy. 50 (11): 3824-3832
APA: Vidal, F; Domingo, JC; Guallar, J; Saumoy, M; Cordobilla, B; de la Rosa, RS; Giralt, M; Alvarez, ML; López-Dupla, M; Torres, F; Villarroya, F; Cihlar, (2006). In vitro cytotoxicity and mitochondrial toxicity of tenofovir alone and in combination with other antiretrovirals in human renal proximal tubule cells. Antimicrobial Agents And Chemotherapy, 50(11), 3824-3832. DOI: 10.1128/AAC.00437-06
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Article's DOI: 10.1128/AAC.00437-06
Entity: Universitat Rovira i Virgili
Journal publication year: 2006
Publication Type: Journal Publications
Repositori URV