title: 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: Department of Epidemiology and Statistics, North China Coal Medical University, 57 Jian-she Road, Tangshan 063000, China.
authors: Bing
authors: B
authors: Zhang
authors: Shufeng
authors: S
authors: Sun
authors: Lihong
authors: L
authors: Shen
authors: Xiangyu
authors: X
authors: Zu
authors: Yi
authors: Y
authors: Chen
authors: Jinqi
authors: J
authors: Hao
authors: Xiaolin
authors: X
authors: Huang
authors: Fumin
authors: F
authors: Feng
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000995:Antitubercular Agents; D000410:Alanine Transaminase; D007538:Isoniazid