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Adv Pharm Bull. 2024;14(1): 224-230.
doi: 10.34172/apb.2024.003
  Abstract View: 418
  PDF Download: 331

Research Article

The Role of the JAK-STAT Signaling Pathway in the Protective Effects of Hepatic Ischemia Post-conditioning Against the Injury Induced by Ischemia/Reperfusion in the Rat Liver

Neda Ghasemi Pour Afshar 1 ORCID logo, Hossein Ali Arab 1* ORCID logo, Akram Vatannejad 1* ORCID logo, Ghorbangol Ashabi 2 ORCID logo, Ali akbar Golabchifar 1 ORCID logo

1 Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
2 Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
*Corresponding Authors: Hossein Ali Arab, Email: harab@ut.ac.ir; Akram Vatannejad, Email: vatannejad@ut.ac.ir

Abstract

Purpose: Hepatic ischemic post-conditioning (IPOC) is shown to protect the liver from injury induced by ischemia/reperfusion (IR). However, the mechanism underlying this protection has remained elusive. The present study aimed to investigate the role of the interleukin 6-Janus kinase-signal transducers and activators of transcription (IL-6-JAK-STAT) pathway in the protective effect of hepatic IPOC against the IR-induced injury in the liver.

Methods: Twenty-five rats were randomly divided into 5 groups of (1) sham-operated, (2) IR, (3) IR+hepatic IPOC, (4) IR+tofacitinib (TOFA), and (5) IR+TOFA+hepatic IPOC. The changes induced by IR and the effects of different treatments were assessed by enzyme release, histopathological observations, the serum level of IL-6, and the occurrence of apoptosis detected via the expression of the Bax/Bcl-2 ratio.

Results: The hepatic IPOC improved the liver injury induced by IR as shown by histological changes, reduction of IL-6 level, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) compared to the IR group (P<0.001, P<0.05, P<0.05, respectively). There was also downregulation of the Bax/Bcl2 ratio in the rats exposed to IR+hepatic IPOC compared with those in the IR group (P<0.05). However, TOFA, an inhibitor of JAK-STAT activity, inhibited the protective effect of hepatic IPOC.

Conclusion: It suggests that the protective effect of hepatic IPOC against IR-induced injury may be mediated by activating the IL-6-JAK-STAT pathway.

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Submitted: 08 Nov 2022
Revision: 02 Jun 2023
Accepted: 14 Jul 2023
ePublished: 19 Jul 2023
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