Alteration of connexins gene expression by silibinin during hepatic warm ischemia-reperfusion injury in the rat model

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Keywords

Connexin
Gap junction
Ischemia-reperfusion
Silibinin

How to Cite

Ghobadi A., MousaviA., Mosavi H., Malekzadeh Shafaroudi M., & Khonakdar-TarsiA. (2021). Alteration of connexins gene expression by silibinin during hepatic warm ischemia-reperfusion injury in the rat model. Iranian Red Crescent Medical Journal, 23(4). https://doi.org/10.32592/ircmj.2021.23.4.250

Abstract

Background: Ischemia-reperfusion injury (IRI) is an injurious phenomenon that is the primary determinant of liver dysfunction after surgery and transplantation. The present evidence demonstrated that connexin 43 (Cx43), Cx32, and Cx26 are the essential gap junction proteins involved in the liver IRI. This study aimed to characterize the beneficial effects of silibinin on Cx43, Cx32, and Cx26 gene expression during warm hepatic ischemia-reperfusion (IR).  

Materials and Methods: A total of 32 male Wistar rats weighing 250-300 g were randomly divided into four equal groups of eight animals in each group as follows: 1) control group (laparotomy+normal saline), 2) laparotomy+silibinin (30 mg/kg) (SILI), 3) liver IR procedure+normal saline (IR), and 4) liver IR procedure+silibinin (30 mg/kg) (IR+SILI). After 1 h of ischemia followed by 3 h of reperfusion, blood samples and tissue sections were gathered to assess the serum liver markers and evaluate the liver histological changes as well as gene expression, respectively.

Results: The obtained data proved no considerable differences between control and SILI groups in all experiments. Furthermore, the gene expression of Cx26, Cx32, and Cx43 was significantly induced in the IR group, compared to the control group. Silibinin markedly reduced Cx26 and Cx32 mRNA expression, whereas increased Cx43 mRNA expression. Moreover, serum alanine aminotransferase and aspartate aminotransferase levels were markedly elevated in the IR group (P<0.001), compared to the control group. However, in the IR+SILI group, silibinin could significantly decline these elevations, compared to the IR group. In addition, silibinin diminished hepatic tissue damages during IR.

Conclusion: Silibinin could attenuate liver injury through better cell-to-cell communication via lowering Cx32 and Cx26, as well as increasing Cx43 gene expression, respectively.

https://doi.org/10.32592/ircmj.2021.23.4.250

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