Effects of Silibinin on Nitric Oxide Synthase Genes Expression during Hepatic Warm Ischemia-reperfusion in Adult Male Rats

Background and Ischemia-reperfusion injuries (I/RI) are the major causes of liver failure after various types of liver surgeries, particularly liver transplantation. Reactive oxygen species (ROS) are the major causes of such injuries, therefore, antioxidant therapy to attenuate hepatic lesions is preferred. We aimed to evaluate the effects of silibinin, a potent radical scavenger, on liver damages and endothelial and inducible nitric oxide synthase (eNOS and iNOS) genes expression after liver I/R.
In this experimental study, the rats were divided into four groups (n=8 per group). Group1 Vehicle: the rats underwent laparotomy and received DMSO10%, Group 2 SILI: the animals received silibinin alongside laparotomy, Group3 I/R: the rats received DMSO10% and subjected to liver I/R procedure, and group 4 I/R䢂: this group received both silibinin and liver I/R simultaneously. Silibinin (50 mg/kg I.P) was administered twice in all rats. After 1 h ischemia and 5 h reperfusion, blood samples were collected to evaluate serum AST and ALT levels and liver sections were taken to analyze the eNOS and iNOS gene expressions and histological examinations.
There were no significant differences in all parameters between Vehicle and SILI groups (p>0.05). But serum AST and ALT increased significantly in I/R group compared with those in vehicle group. Treatment with silibinin could considerably reduce these markers. Histological damages during I/R improved by silibinin. The iNOS gene was found to be overexpressed whereas eNOS expression decreased in I/R group compared with those in the vehicle group. Silibinin treatment could decline iNOS expression but could not significantly affect eNOS expression (p>0.05).
Silibinin protects liver from I/RI. It may decrease iNOS adverse effects by suppressing its expression.