Acetaminophen induced cytotoxicity and altered gene expression in cultured cardiomyocytes of h(9)c(2) cells.
OBJECTIVE
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 (H(9)C(2) cells) after exposure to acetaminophen.


METHODS
H(9)C(2) 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 H(9)C(2) cells.
Department of Pediatrics, Eulji University College of Medicine, Daejeon, Korea.
Seon Mi
SM
Jin
Kwangsik
K
Park