Effects of Ischemic Post-conditioning and Thymoquinone on Liver Ischemia Reperfusion Injury in Rats


Tığ N., KÜÇÜK A., TEKİN E., YIĞMAN Z., ARSLAN M.

Bratislava Medical Journal, 2025 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Publication Date: 2025
  • Doi Number: 10.1007/s44411-025-00150-4
  • Journal Name: Bratislava Medical Journal
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE
  • Keywords: Gasdermin D, Liver ischemia reperfusion injury, Post-conditioning, Rat, Thymoquinone
  • Kütahya Health Sciences University Affiliated: Yes

Abstract

Aim: This study aimed to investigate the mechanisms and compare the efficacy of post-conditioning and thymoquinone (TQ) in a rat model of liver IR injury induced by the Pringle maneuver. Methods: Twenty eight male Sprague–Dawley rats were divided into 4 groups as sham, ischemia, post-conditioning and TQ + ischemia. Liver IR injury was induced with the closing of liver pedicle (15 min ischemia and 60 min reperfusion). Post-conditioning was provided by applying 1 min reperfusion-1 min ischemia in 3 repetitions. TQ was administered as 20 mg/kg/day by oral gavage during 10 days. MDA, GSH, TNF-α, SOD and CAT were measured. Hematoxylin–eosin staining was performed, and p53 and NF-κB were investigated immunohistochemically. Gasdermin D protein were evaluated via Western blot. The data were evaluated via one-way ANOVA test and then posthoc LSD test. Results: Liver MDA and TNF-α, and plasma TNF-α levels increased in the ischemia group, while decreased with post-conditioning and TQ (p < 0.05). Liver GSH levels, SOD, and CAT activities, and plasma SOD and CAT activities were significantly decreased in the ischemia group, while increased with post-conditioning and TQ (p < 0.05). Gasdermin D levels increased in the ischemia group compared to the sham group, but decreased with post-conditioning and TQ (p < 0.05). The histopathological damage increased in the ischemia group, while post-conditioning and TQ reduced this damage (p < 0.05). p53 and NF-κB immunopositive hepatocytes increased in the ischemia group and decreased with post-conditioning and TQ (p < 0.05). Conclusions: Post-conditioning and TQ showed ameliorative effects on liver IR injury, via reducing inflammation, oxidative stress, and the inflammatory cell death pathway pyroptosis.