Environ Health Toxicol.  2012 ;27(1):e2012011.

Acetaminophen Induced Cytotoxicity and Altered Gene Expression in Cultured Cardiomyocytes of H9C2 Cells

Affiliations
  • 1Department of Pediatrics, Eulji University College of Medicine, Daejeon, Korea.
  • 2College of Pharmacy, Dongduk Women's University, Seoul, Korea. kspark@dongduk.ac.kr

Abstract


OBJECTIVES
Hepatotoxicity of acetaminophen has been widely studied. However, the adverse effects on the heart have not been sufficiently evaluated. This study was performed to investigate cytotoxicity and alterations of gene expression in cultured cardiomyocytes (H9C2 cells) after exposure to acetaminophen.
METHODS
H9C2 cells were incubated in a 10 mM concentration of acetaminophen for the designated times (6, 12, and 24 hours), and cytotoxicity was determined by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Alteration of gene expression was observed by microarray analysis, and RT-PCR was performed for the three representative oxidative stress-related genes at 24 hours after treatment.
RESULTS
It revealed that acetaminophen was toxic to cardiomyocytes, and numerous critical genes were affected. Induced genes included those associated with oxidative stress, DNA damage, and apoptosis. Repressed genes included those associated with cell proliferation, myocardial contraction, and cell shape control.
CONCLUSIONS
These findings provide the evidences of acetaminophen-induced cytotoxicity and changes in gene expression in cultured cardiomyocytes of H9C2 cells.

Keyword

Acetaminophen; Cardiomyocyte; Gene expression; In vitro; Toxicity

MeSH Terms

Acetaminophen
Apoptosis
Benzeneacetamides
Cell Proliferation
Cell Shape
DNA Damage
Gene Expression
Heart
Microarray Analysis
Myocardial Contraction
Myocytes, Cardiac
Oxidative Stress
Piperidones
Acetaminophen
Benzeneacetamides
Piperidones
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