Identification of modulated mRNAs and proteins in human primary hepatocytes treated with non-steroidal anti-inflammatory drugs Hye Jin Cha Joon-Ik Ahn Jae-Young Jeong Min-Gyeong Park Eun Jung Kim Hoil Kang Hyung Soo Kim Won-Keun Seong Ho-Sang Jeong Email author Original Paper First Online: 02 October 2015 Received: 11 May 2015 Accepted: 01 July 2015 DOI :
10.1007/s13273-015-0033-3
Cite this article as: Cha, H.J., Ahn, JI., Jeong, JY. et al. Mol. Cell. Toxicol. (2015) 11: 335. doi:10.1007/s13273-015-0033-3 Abstract Drug-induced liver injury (DILI) is the most common adverse event causing drug disapprovals and withdrawals. roughly 10% of drug-induced hepatotoxicity is non-steroidal anti-inflammatory drug (NSAID)-related. To find NSAID-induced hepatotoxic markers, we analyzed gene and protein expression levels using human primary hepatocytes treated with 6 NSAIDs. To examine cellular responses to drug treatments, we conducted cell viability assay. Hepatocytes treated with diclofenac and sulindac showed significantly lower cell viability than those treated by other drugs. From the PCR data, a total of 29 genes were significantly modulated by diclofenac and sulindac. In addition, we treated human primary hepatocytes with representative non-NSAID hepatotoxic drugs such as acetaminophen, valporic acid, and flutamide and performed real-time PCR to select NSAID-specific hepatotoxic markers. The expressions of 4 genes (ABCB1 , LPL , HYOU1 , GADD45A ) and 3 proteins (LPL, HYOU1, GADD45A) showed significant modulation. our findings may provide molecular mechanisms involved in NSAID-induced hepatotoxicity.
Keywords Non-steroidal anti-inflammatory drugs Hepatotoxicity Human primary hepatocytes Mechanism
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Authors and Affiliations Hye Jin Cha Joon-Ik Ahn Jae-Young Jeong Min-Gyeong Park Eun Jung Kim Hoil Kang Hyung Soo Kim Won-Keun Seong Ho-Sang Jeong Email author 1. Pharmacological Research Division, National Institution of Food and Drug Safety Evaluation Ministry of Food and Drug Safety Chungju Korea