Liver international : official journal of the International Association for the Study of the Liver · 2008
Effect of adrenomedullin on hepatic damage in hepatic ischaemia/reperfusion injury in rats.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Kerem Mustafa, Bedirli Abdulkadir, Pasaoglu Hatice, Ofluoğlu Ebru, Yilmazer Demet, Salman Bulent, Yilmaz Tonguc Utku
Аннотация
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-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).
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.
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).
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.
Предметные рубрики MeSH
AdrenomedullinAnimalsArginaseAspartate AminotransferasesBlood Flow VelocityDisease Models, AnimalDrug Therapy, CombinationEndothelin-1Enzyme InhibitorsInterleukin-1betaLiver DiseasesMaleMalondialdehydeNG-Nitroarginine Methyl EsterNitric OxideOxidative StressRatsRats, WistarReperfusion InjuryTumor Necrosis Factor-alphaVasodilator Agents