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Article Open Access

FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway

  • Authors:
    • Xiangmin He
    • Kai Kang
    • Dan Pan
    • Yue Sun
    • Bing Chang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110000, P.R. China, Department of Gastroenterology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110000, P.R. China, Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110000, P.R. China
    Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 67
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    Published online on: March 17, 2022
       https://doi.org/10.3892/ijmm.2022.5123
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Abstract

As the current clinical treatment of acetaminophen (APAP)‑induced liver injury (AILI) has its limitations, new and effective treatment methods are required. Fingolimod (FTY720) is an immunosuppressive drug developed in recent years that has been shown to have a protective effect against ischemia/reperfusion liver injury. However, the role of FTY720 in AILI remains unclear. The aim of the present study was to determine whether FTY720 has a protective effect on AILI. AILI was induced using intraperitoneal injection of 300 mg/kg APAP in male C57BL/6J mice. Following APAP challenge, the mice were administered 5 mg/kg FTY720 for 30 min. Protein expression levels were measured using western blot analysis. Cell viability was examined using Cell Counting Kit‑8 assays. mRNA levels were measured using reverse transcription‑quantitative PCR. Inflammation levels were evaluated using immunohistochemistry. Cell death and reactive oxygen species levels were examined using immunofluorescence. Furthermore, laser scanning intravital microscopy was used to directly observe immune cell recruitment. APAP treatment increased the serum levels of alanine transaminase and aspartate transaminase at the 6‑ and 12‑h time‑points, suggesting liver tissue damage. However, FTY720 attenuated the liver injury induced by APAP by reducing the recruitment of immune cells and the release of pro‑inflammatory cytokines and chemokines. FTY720 activated JAK2/STAT3 signaling and regulated the expression of BAX, BCL‑2 and p65 to inhibit apoptosis and inflammation. In addition, compared with APAP treatment, the viability of primary hepatocytes treated with APAP and FTY720 was increased. Inhibition of JAK2/STAT3 signaling attenuated the protective, antioxidant effects of FTY720. In conclusion, FTY720 reduced liver injury by regulating the JAK2/STAT3 signaling pathway. This compound was capable of inhibiting oxidative stress to reduce hepatocyte death and the infiltration of neutrophils in the liver.
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Copy and paste a formatted citation
Spandidos Publications style
He X, Kang K, Pan D, Sun Y and Chang B: FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway. Int J Mol Med 49: 67, 2022.
APA
He, X., Kang, K., Pan, D., Sun, Y., & Chang, B. (2022). FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway. International Journal of Molecular Medicine, 49, 67. https://doi.org/10.3892/ijmm.2022.5123
MLA
He, X., Kang, K., Pan, D., Sun, Y., Chang, B."FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway". International Journal of Molecular Medicine 49.5 (2022): 67.
Chicago
He, X., Kang, K., Pan, D., Sun, Y., Chang, B."FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway". International Journal of Molecular Medicine 49, no. 5 (2022): 67. https://doi.org/10.3892/ijmm.2022.5123
Copy and paste a formatted citation
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Spandidos Publications style
He X, Kang K, Pan D, Sun Y and Chang B: FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway. Int J Mol Med 49: 67, 2022.
APA
He, X., Kang, K., Pan, D., Sun, Y., & Chang, B. (2022). FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway. International Journal of Molecular Medicine, 49, 67. https://doi.org/10.3892/ijmm.2022.5123
MLA
He, X., Kang, K., Pan, D., Sun, Y., Chang, B."FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway". International Journal of Molecular Medicine 49.5 (2022): 67.
Chicago
He, X., Kang, K., Pan, D., Sun, Y., Chang, B."FTY720 attenuates APAP‑induced liver injury via the JAK2/STAT3 signaling pathway". International Journal of Molecular Medicine 49, no. 5 (2022): 67. https://doi.org/10.3892/ijmm.2022.5123
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