Effect of dexamethasone on the endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) genes expression during hepatic warm ischemia/reperfusion in rat

Background: Hepatic ischemia/reperfusion injury (I/RI) is a multifactorial pathophysiologic process which can lead to liver damage and dysfunction. This study examined the protective effect of dexamethasone on the gene expression of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) and on the liver tissue damage during warm hepatic I/R. Materials and Methods: A total of 32 male Wistar rats was randomly divided into four groups of eight: SHAM: the group receiving saline; DEX: the group receiving dexamethasone (8 mg/kg); I/R: Ischemia-reperfusion insulted group; and DEX + I/R: I/R group receiving dexamethasone. After 3 h of reperfusion followed by 60 min of ischemia, serum and ischemic tissue were collected. Serum was used to determine the hyaluronic acid (HA), aspartate and alanine aminotransferases (AST and ALT). To evaluate the eNOS and ET-1 gene expression, the total RNA was extracted from the liver tissue, cDNA was synthesized and real-time PCR was performed. Tissue staining was performed by the Hematoxylin and Eosin stain. Results: I/R increased serum AST, ALT and HA in I/R group compared with that in the SHAM group (P < 0.001). Dexamethasone significantly reduced the indicators in DEX + IR group (P < 0.001). In addition, the gene expression of the eNOS and ET-1 increased during I/R. Dexamethasone could significantly decrease the ET-1, but not eNOS gene expression in the DEX + IR group. Conclusions: Dexamethasone can decline hepatic I/RI by protecting the sinusoidal endothelial glycocalyx and modifying the expression of ET-1. Given that the reactive oxygen species (ROS) are the main cause of glycocalyx degradation and ET-1 is the regulator of hepatic perfusion, thus, dexamethasone has antioxidant properties and helps proper hepatic perfusion after ischemia to maintain.