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DNA methylation in the rat livers induced by low dosage isoniazid treatment
- Source :
- Environmental Toxicology and Pharmacology. 32:486-490
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
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.
- Subjects :
- Male
Drug
Low dosage
Side effect
Health, Toxicology and Mutagenesis
media_common.quotation_subject
Antitubercular Agents
Pharmacology
Biology
Toxicology
Oral gavage
Rats, Sprague-Dawley
Isoniazid
medicine
Animals
media_common
Liver injury
Dose-Response Relationship, Drug
Alanine Transaminase
General Medicine
Methylation
DNA Methylation
medicine.disease
Rats
Long Interspersed Nucleotide Elements
Liver
DNA methylation
Chemical and Drug Induced Liver Injury
medicine.drug
Subjects
Details
- ISSN :
- 13826689
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Environmental Toxicology and Pharmacology
- Accession number :
- edsair.doi.dedup.....9f6b1fd0f5295ece8834175127e12875