title: Hydrogen Gas Ameliorates Hepatic Reperfusion Injury After Prolonged Cold Preservation in Isolated Perfused Rat Liver.
abstract: Hydrogen gas reduces ischemia and reperfusion injury (IRI) in the liver and other organs. However, the precise mechanism remains elusive. We investigated whether hydrogen gas ameliorated hepatic I/R injury after cold preservation. Rat liver was subjected to 48-h cold storage in University of Wisconsin solution. The graft was reperfused with oxygenated buffer with or without hydrogen at 37° for 90 min on an isolated perfusion apparatus, comprising the H2(+) and H2(-) groups, respectively. In the control group (CT), grafts were reperfused immediately without preservation. Graft function, injury, and circulatory status were assessed throughout the perfusion. Tissue samples at the end of perfusion were collected to determine histopathology, oxidative stress, and apoptosis. In the H2(-) group, IRI was indicated by a higher aspartate aminotransferase (AST), alanine aminotransferase (ALT) leakage, portal resistance, 8-hydroxy-2-deoxyguanosine-positive cell rate, apoptotic index, and endothelial endothelin-1 expression, together with reduced bile production, oxygen consumption, and GSH/GSSG ratio (vs. CT). In the H2(+) group, these harmful changes were significantly suppressed [vs. H2(-)]. Hydrogen gas reduced hepatic reperfusion injury after prolonged cold preservation via the maintenance of portal flow, by protecting mitochondrial function during the early phase of reperfusion, and via the suppression of oxidative stress and inflammatory cascades thereafter.
authors.affiliation: Department of Gastroenterological Surgery I.
authors.forename: Shingo
authors.initials: S
authors.lastname: Shimada
authors.affiliation: Department of Gastroenterological Surgery I.
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakayama
authors.affiliation: Transplant Surgery, Hokkaido University Graduate School of Medicine.
authors.forename: Moto
authors.initials: M
authors.lastname: Fukai
authors.affiliation: Central Clinical Facilities, Division of Organ Transplantation, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shimamura
authors.affiliation: Department of Gastroenterological Surgery I.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Surgical Gastroenterology and Transplantation, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fukumori
authors.affiliation: Department of Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo.
authors.forename: Maki
authors.initials: M
authors.lastname: Shibata
authors.affiliation: Transplant Surgery, Hokkaido University Graduate School of Medicine.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Laboratory of Cancer Research, Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido.
authors.forename: Taichi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: St. Maria Hospital Laboratory, Kurume, Fukuoka, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
authors.affiliation: Department of Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo.
authors.forename: Ikuroh
authors.initials: I
authors.lastname: Ohsawa
authors.affiliation: Department of Gastroenterological Surgery I.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003080:Cold Temperature; D004867:Equipment Design; D005978:Glutathione / Q000494:pharmacology; D006859:Hydrogen / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008111:Liver Function Tests; D008297:Male; D009926:Organ Preservation / Q000295:instrumentation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D018384:Oxidative Stress; D010101:Oxygen Consumption; D010477:Perfusion / Q000295:instrumentation / Q000379:methods*; D020011:Protective Agents / Q000494:pharmacology*; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D007328:Insulin; D019188:Organ Preservation Solutions; D020011:Protective Agents; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D006859:Hydrogen; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose
keywords: Cold ischemia reperfusion injury; Endothelin-1; Hydrogen gas; Liver