BACKGROUND: Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) solution, HTK-N, has been developed. This solution contains N-acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury. METHODS: Microvesicular steatosis was induced by a single dose of ethanol (8 g/kg BW). Livers were harvested and stored at 4 °C for 8 h with HTK or HTK-N before transplantation. Tissue and blood samples were taken at 1, 8, and 24 h after reperfusion to compare serum liver enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), standard histology, and immunohistochemistry for myeloperoxidase (MPO), caspase-3, and inducible nitric oxide synthase. Survival was compared after 1 week. For statistics, Analysis of Variance and t test were used. RESULTS: HTK-N improved survival from 12.5% in HTK to 87.5% (p < 0.05). Furthermore, liver enzymes were decreased to 2-75% of HTK values (p < 0.05). Necrosis and leukocyte infiltration and MPO, caspase-3, and iNOS expression after transplantation were decreased (p < 0.05). CONCLUSIONS: This study demonstrates that HTK-N protects liver grafts with microvesicular steatosis caused by acute toxic injury from cold ischemic injury better than standard HTK most likely via inhibition of hypoxic injury and oxidative stress and amelioration of the inflammatory reaction occurring upon reperfusion.
BACKGROUND:Ischemia/reperfusion injury is an obstacle especially in steatotic livers, including those with steatosis induced by acute toxic stress. Recently, a modified histidine-tryptophan-ketoglutarate (HTK) solution, HTK-N, has been developed. This solution contains N-acetylhistidine, amino acids, and iron chelators. This study was designed to test the effects of HTK-N on preservation injury to rat livers after acute toxic injury. METHODS:Microvesicular steatosis was induced by a single dose of ethanol (8 g/kg BW). Livers were harvested and stored at 4 °C for 8 h with HTK or HTK-N before transplantation. Tissue and blood samples were taken at 1, 8, and 24 h after reperfusion to compare serum liver enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), standard histology, and immunohistochemistry for myeloperoxidase (MPO), caspase-3, and inducible nitric oxide synthase. Survival was compared after 1 week. For statistics, Analysis of Variance and t test were used. RESULTS: HTK-N improved survival from 12.5% in HTK to 87.5% (p < 0.05). Furthermore, liver enzymes were decreased to 2-75% of HTK values (p < 0.05). Necrosis and leukocyte infiltration and MPO, caspase-3, and iNOS expression after transplantation were decreased (p < 0.05). CONCLUSIONS: This study demonstrates that HTK-N protects liver grafts with microvesicular steatosis caused by acute toxic injury from cold ischemic injury better than standard HTK most likely via inhibition of hypoxic injury and oxidative stress and amelioration of the inflammatory reaction occurring upon reperfusion.
Authors: S Natori; M Selzner; K L Valentino; L C Fritz; A Srinivasan; P A Clavien; G J Gores Journal: Transplantation Date: 1999-07-15 Impact factor: 4.939
Authors: N Enomoto; K Ikejima; S Yamashina; A Enomoto; T Nishiura; T Nishimura; D A Brenner; P Schemmer; B U Bradford; C A Rivera; Z Zhong; R G Thurman Journal: Am J Physiol Gastrointest Liver Physiol Date: 2000-07 Impact factor: 4.052
Authors: R Carini; G Bellomo; A Benedetti; R Fulceri; A Gamberucci; M Parola; M U Dianzani; E Albano Journal: Hepatology Date: 1995-04 Impact factor: 17.425
Authors: James B Burch; Erik Svendsen; Paul D Siegel; Sara E Wagner; Susanna von Essen; Thomas Keefe; John Mehaffy; Angelica Serrano Martinez; Mary Bradford; Laura Baker; Brian Cranmer; Rena Saito; John Tessari; Prinz Linda; Colene Andersen; Opal Christensen; Niels Koehncke; Stephen J Reynolds Journal: J Toxicol Environ Health A Date: 2010
Authors: Alexander Kaltenborn; Jill Gwiasda; Volker Amelung; Christian Krauth; Frank Lehner; Felix Braun; Jürgen Klempnauer; Benedikt Reichert; Harald Schrem Journal: BMC Gastroenterol Date: 2014-09-28 Impact factor: 3.067