DNA methylation in the rat livers induced by low dosage isoniazid treatment.

Abstract:

:As a first-line anti-tuberculosis drug, isoniazid has a serious adverse side effect: hepatotoxicity. Therefore, the assessment and monitoring of hepatotoxicity from isoniazid to prevent liver injury are great concerns. In this experiment, we compared the levels of ALT in plasma and DNA methylation. 30 male SD rats were allocated randomly into two groups, a control group and an isoniazid group, and treated, respectively, with pure water and isoniazid at low dosage (10 mg/(kg day)) for 42 days by oral gavage. Five rats per group were sacrificed after 14, 28, and 42 days of isoniazid treatment. The levels of methylation in the genome and LINE-1 were measured, in which hypomethylation in the whole genome and LINE-1 repetitive sequences was observed in the INH group during the later period of the experiment (the 42nd day) accompanied with pathological changes in the liver. Thus, our results suggest that low dose of isoniazid can induce liver injury and that level of DNA methylation may be a more sensitive marker for monitoring drug-induced hepatotoxicity than aminotransferase.

authors

Zhang B,Sun S,Shen L,Zu X,Chen Y,Hao J,Huang X,Feng F

doi

10.1016/j.etap.2011.07.001

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

486-90

issue

3

eissn

1382-6689

issn

1872-7077

pii

S1382-6689(11)00107-4

journal_volume

32

pub_type

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