title: Liraglutide attenuates partial warm ischemia-reperfusion injury in rat livers.
abstract: Ischemia-reperfusion (IR) injury constitutes the most important cause of primary dysfunction of liver grafts. In this study, we have addressed the possible hepatoprotective action of liraglutide against partial warm hepatic IR injury in male rats. Rats were randomly assigned into: sham, IR, and liraglutide-pretreated IR groups. Liraglutide was administered 50 μg/kg s.c. twice daily for 14 days, and then, hepatic IR was induced by clamping portal vein and hepatic artery to left and median lobes for 30 min followed by reperfusion for 24 h. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) activities were determined. Malondialdehyde (MDA) level, reduced glutathione (GSH) content, tumor necrosis factor-α (TNF-α), phosphoralated Akt (p-Akt), and caspase-3 levels of the liver were determined. Hematoxylin and eosin (H&E) stained sections from liver were examined as well as immunohistochemical sections for detection of Bcl-2 expression. IR injury increased ALT, AST, and GGT while decreased GSH and p-Akt with increase in MDA, TNF-α, and caspase-3 levels in the liver with necrosis and inflammatory cellular infiltration with decreased Bcl-2 expression. Pretreatment with liraglutide decreased ALT, AST, and GGT activities while increased glutathione content and Akt activation with decrements in MDA, TNF-α, and caspase-3 levels with attenuation of necrosis and inflammation while enhanced Bcl-2 expression in the liver. Liraglutide protects against IR injury of the liver through antiinflammatory and antioxidant actions as well as inhibition of apoptosis.
authors.affiliation: Department of Pharmacology, Faculty of Medicine-Zagazig University, Zagazig, Egypt. ahmedma_72@yahoo.com.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Abdelsameea
authors.affiliation: Department of Pharmacology, Faculty of Medicine-Zagazig University, Zagazig, Egypt.
authors.forename: Noha A T
authors.initials: NA
authors.lastname: Abbas
authors.affiliation: Department of Pathology, Faculty of Medicine-Zagazig University, Zagazig, Egypt.
authors.forename: Samar M
authors.initials: SM
authors.lastname: Abdel Raouf
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D000069450:Liraglutide / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D052096:Warm Ischemia; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000069450:Liraglutide; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione
keywords: Apoptosis; Caspase-3; Ischemia-reperfusion injury; Liraglutide; Malondialdehyde