Effect of adrenomedullin on hepatic damage in hepatic ischaemia/reperfusion injury in rats


Kerem M., Bedirli A., Pasaoglu H., Ofluoglu E., Yilmazer D., Salman B., ...Daha Fazla

LIVER INTERNATIONAL, cilt.28, ss.972-981, 2008 (SCI İndekslerine Giren Dergi) identifier identifier identifier

Özet

Aims: 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-1 beta 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). Conclusion: 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.