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

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.