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Las Palmas de Gran Canaria, Spain

Zaouali M.A.,Experimental Hepatic Ischemia Reperfusion Unit | Zaouali M.A.,University of Monastir | Bejaoui M.,Experimental Hepatic Ischemia Reperfusion Unit | Calvo M.,University of Barcelona | And 6 more authors.
World Journal of Gastroenterology | Year: 2014

AIM: To test whether a new rinse solution containing polyethylene glycol 35 (PEG-35) could prevent ischemia-reperfusion injury (IRI) in liver grafts.METHODS: Sprague-Dawley rat livers were stored in University of Wisconsin preservation solution and then washed with different rinse solutions (Ringer's lactate solution and a new rinse solution enriched with PEG-35 at either 1 or 5 g/L) before ex vivo perfusion with Krebs-Heinseleit buffer solution. We assessed the following: liver injury (transaminase levels), mitochondrial damage (glutamate dehydrogenase activity), liver function (bile output and vascular resistance), oxidative stress (malondialdehyde), nitric oxide, liver autophagy (Beclin-1 and LCB3) and cytoskeleton integrity (filament and globular actin fraction); as well as levels of metalloproteinases (MMP2 and MMP9), adenosine monophosphate- Activated protein kinase (AMPK), heat shock protein 70 (HSP70) and heme oxygenase 1 (HO-1).RESULTS: When we used the PEG-35 rinse solution, reduced hepatic injury and improved liver function were noted after reperfusion. The PEG-35 rinse solution prevented oxidative stress, mitochondrial damage, and liver autophagy. Further, it increased the expression of cytoprotective heat shock proteins such as HO-1 and HSP70, activated AMPK, and contributed to the restoration of cytoskeleton integrity after IRI.CONCLUSION: Using the rinse solution containing PEG-35 was effective for decreasing liver graft vulnerability to IRI. © 2014 Baishideng Publishing Group Inc. Source


Mosbah I.B.,Experimental Hepatic Ischemia Reperfusion Unit | Zaouali Ma.,Experimental Hepatic Ischemia Reperfusion Unit | Martel C.,University Paris - Sud | Bjaoui M.,Experimental Hepatic Ischemia Reperfusion Unit | And 5 more authors.
Cell Death and Disease | Year: 2012

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. © 2012 Macmillan Publishers Limited All rights reserved. Source


Zaouali M.A.,Experimental Hepatic Ischemia Reperfusion Unit | Zaouali M.A.,Institute DInvestigacions Biomdiques August Pi i Sunyer IDIBAPS | Ben Mosbah I.,Experimental Hepatic Ischemia Reperfusion Unit | Padrissa-Alts S.,Experimental Hepatic Ischemia Reperfusion Unit | And 9 more authors.
Transplantation Proceedings | Year: 2010

Aim Static preservation solution is critical for liver graft outcomes, especially when steatosis is present. Institut Georges Lopez (IGL)-1 solution protects fatty livers effectively against cold ischemia reperfusion injury. Its benefits are mediated by nitric oxide and prevention of oxidative stress. The supplementation of IGL-1 with epidermal growth factor (EGF) enhances steatotic graft preservation by increasing adenosine triphosphate content, thereby mitigating oxidative stress and mitochondrial damage. Methods After steatotic livers were preserved for 24 hours in IGL-1 solution with or without EGF supplements, they were perfused ex vivo for 2 hours at 37°C. The benefits of EGF were assessed by evidences of hepatic damage and functiontransaminases, bile production, and flow rateas well as by other factors presumably associated with the poor tolerance of fatty livers toward cold ischemia-reperfusion injury (IRI)energy metabolism, mitochondrial damage, oxidative stress, eNOS activity and proinflammatory interleukin (IL) beta content. Results Steatotic livers preserved in IGL-1 solutions supplemented with EGF (10 μg/L) showed lower transaminase levels, greater bile production, and ameliorated flow rates when compared to IGL-1 alone. In addition, energy metabolism deterioration, mitochondrial damage, oxidative stress, and cytokine IL-1 beta release were prevented. Conclusion EGF addition to IGL-1 increased fatty liver graft preservation, thereby reducing steatotic liver damage against cold IRI. © 2010 Elsevier Inc. Source

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