Alteration of ConnexinsGene Expression by Silibinin during Hepatic Warm Ischemia-Reperfusion Injury in a Rat Model

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 Cx26are the essential gap junction proteins involved in the liver IRI.

This study aimed to characterize the beneficial effects of silibinin on Cx43, Cx32, and Cx26gene expression during warm hepatic ischemia-reperfusion (IR).

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 (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.

The obtained data proved no considerable differences between control and SILI groups in all experiments. Furthermore, the gene expression of Cx26, Cx32, and Cx43was significantly induced in the IR group, compared to the control group. Silibinin markedly reduced Cx26and Cx32mRNA expression, whereas increased Cx43mRNA 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.

Silibinin could attenuate liver injury through better cell-to-cell communication via lowering Cx32and Cx26, as well as increasing Cx43gene expression, respectively