Acetaminophen induces JNK/p38 signaling and activates the caspase-9-3-dependent cell death pathway in human mesenchymal stem cells

  • Authors:
    • Giou‑Teng Yiang
    • Yung‑Lung Yu
    • Ko‑Ting Lin
    • Jen‑Ni Chen
    • Wei‑Jung Chang
    • Chyou‑Wei Wei
  • View Affiliations

  • Published online on: June 19, 2015     https://doi.org/10.3892/ijmm.2015.2254
  • Pages: 485-492
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Abstract

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug. Generally, the therapeutic dose of APAP is clinically safe, however, high doses of APAP can cause acute liver and kidney injury. Therefore, the majority of previous studies have focussed on elucidating the mechanisms of APAP‑induced hepatotoxicity and nephrotoxicity, in addition to examining ways to treat these conditions in clinical cases. However, few studies have reported APAP‑induced intoxication in human stem cells. Stem cells are important in cell proliferation, differentiation and repair during human development, particularly during fetal and child development. At present, whether APAP causes cytotoxic effects in human stem cells remains to be elucidated, therefore, the present study aimed to investigate the cellular effects of APAP treatment in human stem cells. The results of the present study revealed that high‑dose APAP induced more marked cytotoxic effects in human mesenchymal stem cells (hMSCs) than in renal tubular cells. In addition, increased levels of hydrogen peroxide (H2O2), phosphorylation of c‑Jun N‑terminal kinase and p38, and activation of caspase‑9/‑3 cascade were observed in the APAP‑treated hMSCs. By contrast, antioxidants, including vitamin C reduced APAP‑induced augmentations in H2O2 levels, but did not inhibit the APAP‑induced cytotoxic effects in the hMSCs. These results suggested that high doses of APAP may cause serious damage towards hMSCs.
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August-2015
Volume 36 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yiang GT, Yu YL, Lin KT, Chen JN, Chang WJ and Wei CW: Acetaminophen induces JNK/p38 signaling and activates the caspase-9-3-dependent cell death pathway in human mesenchymal stem cells. Int J Mol Med 36: 485-492, 2015
APA
Yiang, G., Yu, Y., Lin, K., Chen, J., Chang, W., & Wei, C. (2015). Acetaminophen induces JNK/p38 signaling and activates the caspase-9-3-dependent cell death pathway in human mesenchymal stem cells. International Journal of Molecular Medicine, 36, 485-492. https://doi.org/10.3892/ijmm.2015.2254
MLA
Yiang, G., Yu, Y., Lin, K., Chen, J., Chang, W., Wei, C."Acetaminophen induces JNK/p38 signaling and activates the caspase-9-3-dependent cell death pathway in human mesenchymal stem cells". International Journal of Molecular Medicine 36.2 (2015): 485-492.
Chicago
Yiang, G., Yu, Y., Lin, K., Chen, J., Chang, W., Wei, C."Acetaminophen induces JNK/p38 signaling and activates the caspase-9-3-dependent cell death pathway in human mesenchymal stem cells". International Journal of Molecular Medicine 36, no. 2 (2015): 485-492. https://doi.org/10.3892/ijmm.2015.2254