Formation and role of plasma S-nitrosothiols in liver ischemia-reperfusion injury.
Plasma S-nitrosothiols (RSNOs) may act as a circulating form of nitric oxide that affects vascular function and platelet aggregation. Their role in liver ischemia/reperfusion (I/R) injury is largely unknown. The aim of the present study was to investigate the changes in plasma RSNOs following liver I/R injury. Two groups of New Zealand white rabbits were used (n=6, each): the I/R group underwent 60 min lobar liver ischemia and 7 h reperfusion, while the sham group underwent laparotomy but no liver ischemia. Serial RSNO levels were measured in plasma by electron paramagnetic resonance (EPR) spectrometry, nitrite/nitrates by capillary electrophoresis, hepatic microcirculation by laser Doppler flowmetry, redox state of hepatic cytochrome oxidase by near-infrared spectroscopy, liver iNOS mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) and the oxidation of dihydrorhodamine to rhodamine by fluorescence. The effect of the antioxidant N-acetylcysteine (NAC) on RSNOs formation and DHR oxidation was tested in a third group of animals (n=6) undergoing lobar liver I/R. Hepatic I/R was associated with a significant increase in plasma RSNOs, plasma nitrites, hepatic iNOS mRNA expression, impairment in hepatic microcirculation, decrease in the redox state of cytochrome oxidase, and significant production of rhodamine. The changes were more obvious during the late phase of reperfusion (>4 h). NAC administration decreased plasma RSNOs and oxidation of DHR to RH (P<0.05, 5 and 7 h postreperfusion, respectively). These results suggest that significant upregulation of nitric oxide synthesis during the late phase of reperfusion is associated with impairment in microcirculation and mitochondrial dysfunction. Plasma S-nitrosothiols are a good marker of this nitric oxide-mediated hepatotoxicity.
Glantzounis
Georgios K
GK
Hepatic Hemodynamic Unit, Academic Division of Surgical and Interventional Sciences, University College London, Rowland Hill Street, London NW3 2QG, UK.
Rocks
Sophie A
SA
Sheth
Hemant
H
Knight
Iona
I
Salacinski
Henryk J
HJ
Davidson
Brian R
BR
Winyard
Paul G
PG
Seifalian
Alexander M
AM
D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D003576:Electron Transport Complex IV / Q000378:metabolism; D019075:Electrophoresis, Capillary; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D026361:Reactive Nitrogen Species; D015427:Reperfusion Injury; D026403:S-Nitrosothiols / Q000097:blood*
D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D026361:Reactive Nitrogen Species; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D003576:Electron Transport Complex IV; D000111:Acetylcysteine