2. Academic Validation
  3. Janus kinase inhibitor Tofacitinib alleviated acute hepatitis induced by lipopolysaccharide/D-galactosamine in mice

Janus kinase inhibitor Tofacitinib alleviated acute hepatitis induced by lipopolysaccharide/D-galactosamine in mice

  • Mol Biol Rep. 2022 Dec 12. doi: 10.1007/s11033-022-08086-6.
Xinyue Zhang # 1,  Ling Lin # 1,  Longjiang Li 1,  Kai Hu 2,  Ruyue Shao 3 4,  Li Zhang 1,  Li Tang 1,  Min Zhu 5 6,  Yuhua Ma 7 8,  Yongqiang Yang 9
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Basic Medical College, Chongqing Medical University, Chongqing, PR China.
  • 2 Department of Histology and Embryology, Basic Medical College, Chongqing Medical University, Chongqing, PR China.
  • 3 Clinical Medical School, Chongqing Medical and Pharmaceutical College, Chongqing, PR China.
  • 4 Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing, PR China.
  • 5 Department of Pathology, Karamay Central Hosptial of XinJiang Karamay, Karamay, Xinjiang, PR China.
  • 6 Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, PR China.
  • 7 Department of Pathology, Karamay Central Hosptial of XinJiang Karamay, Karamay, Xinjiang, PR China. 13669904814@163.com.
  • 8 Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, PR China. 13669904814@163.com.
  • 9 Department of Pathophysiology, Basic Medical College, Chongqing Medical University, Chongqing, PR China. fyyyq1984@cqmu.edu.cn.
  • # Contributed equally.
PMID: 36507969 DOI: 10.1007/s11033-022-08086-6
Abstract

Background: The Janus kinase (JAK) is a crucial intracellular signaling hub for numerous cytokines, which is extensively involved in the activation of inflammatory cascade and the induction of inflammatory injury. JAK inhibition provides protective effects in several inflammation-based disorders, but the potential effects of JAK Inhibitor in inflammation-based acute hepatitis remain to be investigated.

Methods and results: Acute hepatitis is induced by Lipopolysaccharide/D-galactosamine (LPS/D-Gal) in mice with or without the JAK Inhibitor Tofacitinib administration. The degree of liver injury, the production of pro-inflammatory cytokines and induction of hepatocytes Apoptosis were determined. The results indicated that treatment with Tofacitinib decreased the levels of aminotransferases, attenuated the histological abnormalities in liver and decreased the plasma levels of TNF-α and IL-6 in LPS/D-Gal-insulted mice. In addition, Tofacitinib suppressed the activation of the Caspase cascade, decreased the level of cleaved Caspase-3, and reduced the count of TUNEL-positive cells.

Conclusion: Treatment with Tofacitinib alleviated LPS/D-Gal-induced acute hepatitis. JAK maybe become a promising target for the control of inflammation-based liver disorders.

Keywords

Acute hepatitis; Apoptosis; Inflammation; JAK; Tofacitinib.

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