Preservation of steatotic livers in IGL-1 solution.
A new Institut Georges Lopez (IGL-1) solution was used to preserve steatotic livers. Steatotic (obese [Ob]) and nonsteatotic (lean [Ln]) livers from Zücker rats (n = 16, 8 Ln and 8 Ob) were preserved for 24 hours at 4 degrees C in University of Wisconsin (UW) or IGL-1 solution, respectively, and then perfused ex vivo for 2 hours at 37 degrees C. Additionally, Ob and Ln livers (n = 16, 8 Ln and 8 Ob) were preserved in IGL-1 plus Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME). Hepatic injury and function (aminotransferases, bile production, bromosulfophthalein clearance), and factors potentially involved in the susceptibility of steatotic livers to ischemia-reperfusion injury, such as oxidative stress, mitochondrial damage, and vascular resistance, were studied. Nitric oxide (NO) production and constitutive and inducible NO synthase were also measured. Steatotic and nonsteatotic livers preserved in IGL-1 solution showed lower transaminases, malondialdehyde, glutamate dehydrogenase levels, and higher bile production than UW-solution-preserved livers. IGL-1 solution protected against oxidative stress, mitochondrial damage and the alterations in vascular resistance associated with cold ischemia-reperfusion. Thus, at the end of reperfusion period, aspartate aminotransferase levels in steatotic livers were 281 +/- 6 U/L in UW vs. 202 +/- 10 U/L in IGL-1 solution. Glutamate dehydrogenase was 463 +/- 75 U/L in UW vs. 111 +/- 4 U/L in IGL-1 solution, and oxidative stress was 3.0 +/- 0.1 nmol/mg prot in UW vs. 2.0 +/- 0.1 nmol/mg prot in IGL-1 solution. These beneficial effects of IGL-1 solution were abolished by the addition of L-NAME, which implicates NO in the benefits of IGL-1. In conclusion, IGL-1 solution provided steatotic livers with better protection against the deleterious effects of cold ischemia-reperfusion injury than did UW solution.
Ben Mosbah
Ismail
I
Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomèdiques August Pí i Sunyer, Barcelona, Spain.
Roselló-Catafau
Joan
J
Franco-Gou
Rosa
R
Abdennebi
Hassen Ben
HB
Saidane
Dalila
D
Ramella-Virieux
Silvina
S
Boillot
Olivier
O
Peralta
Carmen
C
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D015424:Reperfusion; D013696:Temperature; D014655:Vascular Resistance
C504757:IGL-1 solution; D019188:Organ Preservation Solutions; D009569:Nitric Oxide; D008315:Malondialdehyde; D019001:Nitric Oxide Synthase; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase