Pretreatment With Calcitonin Gene-Related Peptide Attenuates Hepatic Ischemia/Reperfusion Injury in Rats

• Published in: Transplantation proceedings Vol. 41; no. 5; pp. 1493 - 1498
• Main Authors: Song, S.W, Guo, K.J, Shi, R, Cheng, Y, Liu, Y.F
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-06-2009; Elsevier
• Subjects: Adenine Nucleotides - metabolism; Alanine Transaminase - metabolism; Animals; Bile - secretion; Biological and medical sciences; Blood Pressure; Calcitonin Gene-Related Peptide - therapeutic use; Cell Death - drug effects; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gastroenterology. Liver. Pancreas. Abdomen; Glucose; In Situ Nick-End Labeling; Lipid Peroxidation - drug effects; Liver - drug effects; Liver - physiology; Liver Circulation - drug effects; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Mannitol; Medical sciences; Organ Preservation Solutions; Other diseases. Semiology; Oxygen Consumption - drug effects; Portal Vein; Potassium Chloride; Procaine; Rats; Rats, Wistar; Reperfusion Injury - prevention & control; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue, organ and graft immunology; Rat; Digestive system; Liver; Rodentia; Cardiovascular disease; Hepatic disease; Calcitonin gene related peptide; Transplantation; Neuropeptide; Vascular disease; Medicine; Vertebrata; Mammalia; Reperfusion; Treatment; Ischemia; Surgery; Animal; Hepatic ischemia reperfusion injury; Digestive diseases; Graft; Pretreatment
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2009.03.056

Abstract Objective Oxygen free radicals and apoptosis play important roles in liver ischemia/reperfusion (I/R) injury. We sought to investigate the protective effect of calcitonin gene-related peptide (CGRP) to attenuate liver I/R injury due to oxygen free radicals and apoptosis. Materials and Methods Harvested rat livers were perfused via the portal vein with 60 mL of 4°C histidine-tryptophan-ketoglutarate (HTK) solution alone in the control group, or with the same solution containing CGRP (3 μg/10 g body weight) in the experimental group. After 24 hours of cold storage, hepatic enzyme leakage, portal venous pressure, oxygen consumption, total adenine nucleotides (TAN), bile production, lipoperoxide (LPO) release, apoptosis, and histochemical changes were evaluated upon 45 minutes of isolated reperfusion. Results Compared with control livers, CGRP-treated organs showed significantly decreased alanine aminotransferase (ALT) and glutamate-lactate dehydrogenase (GLDH) leakage and portal venous pressure (2.0 ± 0.3 vs 4.0 ± 0.4 mm Hg; P < .01), with significantly increased bile production (8.56 ± 0.76 vs 3.34 ± 0.68 μL/g/45 min; P < .01), oxygen consumption (5.14 ± 0.4 vs 2.57 ± 0.2 μL/g/min; P < .01), and total adenine nucleotides (TAN) (11.1 ± 0.71 vs 7.02 ± 0.53 μmol/g; P < .01) upon reperfusion as signs of recovered viability. We observed infrequent positive terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) staining, especially in sinusoidal lining cells (SLC). The percentage of TUNEL-positive cells in the CGRP group was significantly decreased compared with the control group: (4.1 ± 0.67 vs 8.0 ± 1.27; P < .05). Perfusate levels of low molecular weight (LMW) histone-associated DNA fragments (0.36 ± 0.04 vs 0.53 ± 0.06 AU; P < .05) were also decreased, coupled with strong 5′-nucleotidase (5′-NT) and LDH activity staining concentrated on the endothelial cells. LPO release in the perfusate was largely decreased: (0.12 ± 0.02 vs 0.36 ± 0.04 nmoL/g, P < .01). Conclusion CGRP ameliorated liver I/R injury due to reactive oxygen species and apoptosis.