title: IGL-1 solution reduces endoplasmic reticulum stress and apoptosis in rat liver transplantation.
abstract: Injury due to cold ischemia reperfusion (I/R) is a major cause of primary graft non-function following liver transplantation. We postulated that I/R-induced cellular damage during liver transplantation might affect the secretory pathway, particularly at the endoplasmic reticulum (ER). We examined the involvement of ER stress in organ preservation, and compared cold storage in University of Wisconsin (UW) solution and in Institute Georges Lopez-1 (IGL-1) solution. In one group of rats, livers were preserved in UW solution for 8 h at 4 °C, and then orthotopic liver transplantation was performed according to Kamada's cuff technique. In another group, livers were preserved in IGL-1 solution. The effect of each preservation solution on the induction of ER stress, hepatic injury, mitochondrial damage and cell death was evaluated. As expected, we found increased ER stress after liver transplantation. IGL-1 solution significantly attenuated ER damage by reducing the activation of three pathways of unfolded protein response and their effector molecules caspase-12, C/EBP homologous protein-10, X-box-binding protein 1, tumor necrosis factor-associated factor 2 and eukaryotic translation initiation factor 2. This attenuation of ER stress was associated with a reduction in hepatic injury and cell death. Our results show that IGL-1 solution may be a useful means to circumvent excessive ER stress reactions associated with liver transplantation, and may optimize graft quality.
authors.affiliation: Experimental Hepatic Ischemia-Reperfusion Unit, IIBB-CSIC Barcelona, Barcelona, Spain.
authors.forename: I B
authors.initials: IB
authors.lastname: Mosbah
authors.forename: M A
authors.initials: MA
authors.lastname: Zaouali
authors.forename: C
authors.initials: C
authors.lastname: Martel
authors.forename: M
authors.initials: M
authors.lastname: Bjaoui
authors.forename: H B
authors.initials: HB
authors.lastname: Abdennebi
authors.forename: G
authors.initials: G
authors.lastname: Hotter
authors.forename: C
authors.initials: C
authors.lastname: Brenner
authors.forename: J
authors.initials: J
authors.lastname: Roselló-Catafau
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D050377:Cold Ischemia; D003080:Cold Temperature; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D000071701:Regulatory Factor X Transcription Factors; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response / Q000187:drug effects / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C504757:IGL-1 solution; D007328:Insulin; D019188:Organ Preservation Solutions; D000071701:Regulatory Factor X Transcription Factors; D047992:TNF Receptor-Associated Factor 2; D014157:Transcription Factors; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D053454:Caspase 12; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose