The effect of pretreatment with calcitonin gene-related peptide on attenuation of liver ischemia and reperfusion injury due to oxygen free radicals and apoptosis.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
CGRP can ameliorate liver ischemia reperfusion injury due to oxygen free radicals and apoptosis.
Song
ShaoW
S
Department of General Surgery, First Hospital of China Medical University, Nanjing North Street 55, Heping District, Shenyang 110001, P R China. songsw10@hotmail.com
Liu
Ning
N
Liu
Wei
W
Shi
Rui
R
Guo
Ke J
KJ
Liu
Yong F
YF
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D015740:Calcitonin Gene-Related Peptide / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy*
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D015740:Calcitonin Gene-Related Peptide