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Zhonghua Gan Zang Bing Za Zhi. 2012 Oct;20(10):751-4. doi: 10.3760/cma.j.issn.1007-3418.2012.10.009.

[Entecavir treatment causes injury to the mitochondrial DNA of peripheral blood mononuclear cells].

[Article in Chinese]

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  • 1Youan Hospital Affiliated to the Capital Medical University, Beijing, China.

Abstract

OBJECTIVE:

Based on the potential for nucleotide analogues to affect DNA polymerase-gamma, which controls the proliferation of mitochondria, this study aimed to determine whether long-term treatment with entecavir can cause damage to mitochondrial (mt)DNA in the peripheral blood mononuclear cells (PBMCs) of patients with chronic hepatitis B (CHB).

METHODS:

Patients with CHB were divided into three groups according to their history of treatment type and duration: (1) entecavir monotherapy for 2 years, n = 17; (2) entecavir monotherapy for 3 years, n = 17; (3) non-antiviral treatment as control, n = 18. PBMCs were isolated and used to assess the mtDNA content by quantitative real-time PCR of mitochondria-specific genes. Plasma malonaldehyde (MDA) and F2-isoprostanes were measured by enzyme linked immunosorbent assay. Plasma total antioxidant capacity (TAOC) was detected by spectrophotometry.

RESULTS:

The relative quantity (RQ; of mtDNA to nuclear (n)DNA) was significantly lower in the 3-year treatment group (0.5+/-0.3) than in the control group (1.4+/-1.2; F = 5.233, P = 0.009). The RQ was also significantly lower in the 2-year treatment group (0.4+/-0.2) than in the control group (P = 0.004). The level of F2-isoprostanes (ng/mL) was significantly lower in the 3-year treatment group (1.2+/-0.5) than in the control group (3.6+/-2.9, P = 0.002) or the 2-year treatment group (2.4+/-1.3, P = 0.007). The TAOC was significantly different when compared among all three groups (F = 4.326, P = 0.019). The TAOC (IU/mL) in the 3-year treatment group (2.6+/-1.2) was significantly lower than in the control group (5.0+/-3.0 P = 0.005), but was not significantly different than that for the 2-year group (3.2+/-1.6, P = 0.227). The levels of MDA were not significantly different between any of the groups (F = 0.291, P = 0.749).

CONCLUSION:

Long-term treatment with entecavir, up to 3 years, leads to decreased mtDNA content in PBMCs. Since no clinical manifestations of mtDNA toxicity were observed, the consequent damage to the mitochondrial function may be compensated for by yet unknown mechanisms.

PMID:
23207335
[PubMed - indexed for MEDLINE]
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