ShaoW Song1, Ning Liu, Wei Liu, Rui Shi, Ke J Guo, Yong F Liu. 1. Department of General Surgery, First Hospital of China Medical University, Nanjing North Street 55, Heping District, Shenyang 110001, P R China. songsw10@hotmail.com
Abstract
BACKGROUND/AIMS: Hepatic ischemia reperfusion injury (I/R) occurs in the settings of transplantation. Trauma and elective liver resections. Reactive oxygen species (ROS) and apoptosis have been shown to play a major role in organ I/R injury. Calcitonin gene-related peptide (CGRP)--a principal transmitter in sensory nerves and widely distributed in the cardiovascular system, is one of the most potent vasodilators and has been shown to mimic the protective effects of ischemic preconditioning. The purpose of this study was to investigate the protective effect of CGRP in attenuating liver I/R injury due to ROS and apoptosis. METHODOLOGY: Wistar rats underwent 60 minutes of partial warm hepatic ischemia, CGRP (3 microg/10 g body weight) or Lactate Ringer's solution (LR) were given by introvenous injection 1 hour before the initiating of ischemia. After 24 hours of reperfusion, Serum alanine aminotransferase (ALT) level, total adenine nucleotides (TAN), release of lipoperoxides (LPO), nitric oxide (NO), apoptosis and hitochemical change in the liver tissue were evaluated. RESULTS: Serum ALT level was significantly decreased in CGRP-treated rats, the amount of hepaic LPO and NO also decreased significantly compared with control animals. TAN in the liver tissue was increased significantly coupled with strong 5'-nucleotidase (5'NT) and lactate dehydrogenase (LDH) activity staining concentrated on the endothelial cells. Treatment with CGRP effectively inhibit hepatic caspase 3 activity and occurrence of apoptosis. CONCLUSION: CGRP can ameliorate liver ischemia reperfusion injury due to oxygen free radicals and apoptosis.
BACKGROUND/AIMS: Hepatic ischemia reperfusion injury (I/R) occurs in the settings of transplantation. Trauma and elective liver resections. Reactive oxygen species (ROS) and apoptosis have been shown to play a major role in organ I/R injury. Calcitonin gene-related peptide (CGRP)--a principal transmitter in sensory nerves and widely distributed in the cardiovascular system, is one of the most potent vasodilators and has been shown to mimic the protective effects of ischemic preconditioning. The purpose of this study was to investigate the protective effect of CGRP in attenuating liver I/R injury due to ROS and apoptosis. METHODOLOGY:Wistar rats underwent 60 minutes of partial warm hepatic ischemia, CGRP (3 microg/10 g body weight) or Lactate Ringer's solution (LR) were given by introvenous injection 1 hour before the initiating of ischemia. After 24 hours of reperfusion, Serum alanine aminotransferase (ALT) level, total adenine nucleotides (TAN), release of lipoperoxides (LPO), nitric oxide (NO), apoptosis and hitochemical change in the liver tissue were evaluated. RESULTS: Serum ALT level was significantly decreased in CGRP-treated rats, the amount of hepaic LPO and NO also decreased significantly compared with control animals. TAN in the liver tissue was increased significantly coupled with strong 5'-nucleotidase (5'NT) and lactate dehydrogenase (LDH) activity staining concentrated on the endothelial cells. Treatment with CGRP effectively inhibit hepatic caspase 3 activity and occurrence of apoptosis. CONCLUSION:CGRP can ameliorate liver ischemia reperfusion injury due to oxygen free radicals and apoptosis.