Effect of adrenomedullin on hepatic damage in hepatic ischaemia/reperfusion injury in rats.
OBJECTIVE
Adrenomedullin (AM) is a multifunctional peptide with a putative beneficial role after an ischaemic insult. The aim of this study was to evaluate the effect of AM on partial hepatic ischaemia reperfusion (I/R) injury.


METHODS
Rats were subjected to 1 h of 70% hepatic ischaemia, followed by reperfusion or sham. At the end of ischaemia, vehicle (phosphate-buffered saline solution), N-nitro-L-arginine methyl ester (L-NAME) and AM with or without L-NAME were infused via the portal vein. Analysis was performed at pre-ischaemia, ischaemia onset and 1, 2 and 4 h after reperfusion. Hepatic tissue blood flow (HTBF) was evaluated by laser Doppler.


RESULTS
Plasma AM levels in the I/R groups were significantly lower than the levels in the sham group. AM treatment significantly reduced levels of aspartate transaminase and tissue arginase (P<0.05). Significant decreases of tumour necrosis factor-alpha, interleukin-1beta and endothelin-1 levels were also found in the serum. Endothelin-1, malondialdehyde and necrosis were observed more frequently in liver tissue in the AM group than the control (P<0.05). Tissue nitric oxide, energy charge and HTBF were significantly increased in AM treatment experiments (P<0.05).


CONCLUSIONS
The improved HTBF, energy charge and nitric oxide and the reduction of hepatic necrosis, oxidative stress, liver enzymes, endotelin-1 and pro-inflammatory cytokines demonstrate that treatment with AM attenuates liver I/R injury.
Kerem
Mustafa
M
Department of General Surgery, Medical Faculty, Gazi University, Ankara, Turkey. mkerem@gazi.edu.tr
Bedirli
Abdulkadir
A
Pasaoglu
Hatice
H
Ofluoğlu
Ebru
E
Yilmazer
Demet
D
Salman
Bulent
B
Yilmaz
Tonguc Utku
TU
D053607:Adrenomedullin / Q000097:blood / Q000627:therapeutic use*; D000818:Animals; D001119:Arginase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D019332:Endothelin-1 / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053583:Interleukin-1beta / Q000097:blood; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014665:Vasodilator Agents / Q000097:blood / Q000627:therapeutic use*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D053607:Adrenomedullin; D009569:Nitric Oxide; D008315:Malondialdehyde; D001219:Aspartate Aminotransferases; D001119:Arginase; D019331:NG-Nitroarginine Methyl Ester