Comparative effects of adefovir and selected nucleoside inhibitors of hepatitis B virus DNA polymerase on mitochondrial DNA in liver and skeletal muscle cells
| Autor: | T. Cihlar, G. Birkus, Craig S. Gibbs |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Hepatoblastoma
Hepatitis B virus DNA polymerase Hepatitis B virus DNA polymerase Organophosphonates Mitochondria Liver Fialuridine medicine.disease_cause Antiviral Agents DNA Mitochondrial Zalcitabine Hepatitis B Chronic Virology Tumor Cells Cultured medicine Adefovir Humans Muscle Skeletal Nucleic Acid Synthesis Inhibitors Hepatology biology Adenine virus diseases Lamivudine Molecular biology digestive system diseases Infectious Diseases biology.protein Nucleoside medicine.drug |
| Zdroj: | Journal of Viral Hepatitis. 10:50-54 |
| ISSN: | 1365-2893 1352-0504 |
| Popis: | summary. Adefovir is a potent nucleotide analog inhibitor of hepatitis B virus (HBV) DNA polymerase. Its oral prodrug adefovir dipivoxil has been approved for the treatment of chronic HBV infection. In this study, adefovir was characterized for its in vitro effects on mitochondrial DNA (mtDNA) synthesis and compared with the nucleoside analogues lamivudine (3TC), fialuridine (FIAU), and zalcitabine (ddC). No substantial changes in mtDNA content were detected in human hepatoblastoma HepG2 cells and normal human skeletal muscle cells following a 9-day treatment with 0.3–30 μm adefovir, concentrations up to 500-fold higher than the peak serum levels in patients treated with adefovir dipivoxil. Similarly, mtDNA was unchanged in both cell types following treatment with 3TC. In contrast, 30–55% and > 90% reductions in mtDNA were observed following incubation with 30 μm FIAU and ddC, respectively. The effects of FIAU on mtDNA became more pronounced following prolonged 18-day treatment of skeletal muscle cells while the effects of other drugs remained unchanged. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|