Comparative effects of adefovir and selected nucleoside inhibitors of hepatitis B virus DNA polymerase on mitochondrial DNA in liver and skeletal muscle cells

被引：18

作者：

Birkus, G ^{[1
]}

Gibbs, CS ^{[1
]}

Cihlar, T ^{[1
]}

Benhamou, Y ^{[1
]}

Bochet, M ^{[1
]}

Thibault, V ^{[1
]}

机构：

[1] Gilead Sci Inc, Foster City, CA 94404 USA

来源：

JOURNAL OF VIRAL HEPATITIS | 2003年 / 10卷 / 01期

关键词：

3TC; adefovir; FIAU; HBV; mitochondria; nucleoside analog;

D O I：

10.1046/j.1365-2893.2003.00399.x

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 muM 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 muM 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.

引用

页码：50 / 54

页数：5

共 32 条

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