BACKGROUND: To protect hepatocytes from ischemia/reperfusion injury in mice, prolonged delivery of nitric oxide (NO) to the liver was performed by a bolus intravenous injection of polyethylene glycol (PEG)-conjugated bovine serum albumin (BSA) with about 10 NO molecules attached via an S-nitrosothiol linkage (PEG-poly SNO-BSA). METHODS: A hepatic ischemia/reperfusion injury was induced in mice by occluding the portal vein and the hepatic artery for 15 min followed by 6 hours of reperfusion. Each NO donor was injected into the tail vein just before the initiation of the reperfusion at a dose of 2 micromol NO/kg. RESULTS: The ischemia followed by reperfusion resulted in a striking increase in plasma alanine aminotransferase and aspartate aminotransferase activities. S-nitroso-N-acetyl penicillamine and NO-BSA, two classical S-nitrosothiols, had no statistically significant effect in preventing elevation of the markers. In marked contrast, PEG-poly SNO-BSA significantly (P<0.01) suppressed it. In addition, PEG-poly SNO-BSA significantly (P<0.01) reduced the number of neutrophils infiltrating into the liver and prevented the excessive production of NO from inducible NO synthase in the liver. CONCLUSIONS: These results indicate that PEG-poly SNO-BSA can be used to prevent hepatic ischemia/reperfusion injury.
BACKGROUND: To protect hepatocytes from ischemia/reperfusion injury in mice, prolonged delivery of nitric oxide (NO) to the liver was performed by a bolus intravenous injection of polyethylene glycol (PEG)-conjugated bovine serum albumin (BSA) with about 10 NO molecules attached via an S-nitrosothiol linkage (PEG-poly SNO-BSA). METHODS: A hepatic ischemia/reperfusion injury was induced in mice by occluding the portal vein and the hepatic artery for 15 min followed by 6 hours of reperfusion. Each NO donor was injected into the tail vein just before the initiation of the reperfusion at a dose of 2 micromol NO/kg. RESULTS: The ischemia followed by reperfusion resulted in a striking increase in plasma alanine aminotransferase and aspartate aminotransferase activities. S-nitroso-N-acetyl penicillamine and NO-BSA, two classical S-nitrosothiols, had no statistically significant effect in preventing elevation of the markers. In marked contrast, PEG-poly SNO-BSA significantly (P<0.01) suppressed it. In addition, PEG-poly SNO-BSA significantly (P<0.01) reduced the number of neutrophils infiltrating into the liver and prevented the excessive production of NO from inducible NO synthase in the liver. CONCLUSIONS: These results indicate that PEG-poly SNO-BSA can be used to prevent hepatic ischemia/reperfusion injury.
Authors: Jeff S Isenberg; Justin B Maxhimer; Perlita Powers; Maria Tsokos; William A Frazier; David D Roberts Journal: Surgery Date: 2008-09-02 Impact factor: 3.982
Authors: Niels P van der Kaaij; Jolanda Kluin; Jack J Haitsma; Michael A den Bakker; Bart N Lambrecht; Burkhard Lachmann; Ron W F de Bruin; Ad J J C Bogers Journal: Respir Res Date: 2008-03-26
Authors: John D Lang; Alvin B Smith; Angela Brandon; Kelley M Bradley; Yuliang Liu; Wei Li; D Ralph Crowe; Nirag C Jhala; Richard C Cross; Luc Frenette; Kenneth Martay; Youri L Vater; Alexander A Vitin; Gregory A Dembo; Derek A Dubay; J Steven Bynon; Jeff M Szychowski; Jorge D Reyes; Jeffrey B Halldorson; Stephen C Rayhill; Andre A Dick; Ramasamy Bakthavatsalam; Jared Brandenberger; Jo Ann Broeckel-Elrod; Laura Sissons-Ross; Terry Jordan; Lucinda Y Chen; Arunotai Siriussawakul; Devin E Eckhoff; Rakesh P Patel Journal: PLoS One Date: 2014-02-12 Impact factor: 3.240