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Liver transplantation remains the only definitive treatment for end-stage liver diseases. However, the increasing prevalence of fatty liver disease among potential donors exacerbates the shortage of suitable organs. This study evaluates the efficacy of the preservation solution Institut Georges Lopez-2 (IGL-2) compared to Histidine–Tryptophan–Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in mitigating ischemia-reperfusion injury (IRI) in steatotic livers. Using Zucker Obese rat livers, we assessed the impact of 24-h static cold storage (SCS) with each solution on transaminase release, glutathione redox balance, antioxidant enzyme activity, lipoperoxidation, and inflammation markers. IGL-2 and UW solutions demonstrated reduced transaminase and lactate levels compared to HTK, indicating better preservation of liver integrity. IGL-2 maintained a higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, suggesting more effective management of oxidative stress. Antioxidant enzyme activities catalase, superoxide dismutase, and glutathione peroxidase (CAT, SOD, GPX) were higher in IGL-2 preserved livers, contributing to decreased oxidative damage. Lipid peroxidation markers and inflammatory markers were lower in IGL-2 than in HTK, indicating reduced oxidative stress and inflammation. Additionally, improved mitochondrial function was observed in the IGL-2 group, correlating with reduced reactive oxygen species (ROS) production and lipid peroxidation. These findings suggest that IGL-2 offers superior preservation of liver viability, reduces oxidative stress, and minimizes inflammation compared to HTK and UW solutions. By maintaining a higher ratio of reduced glutathione and antioxidant enzyme activity, IGL-2 effectively mitigates the harmful effects of ischemia-reperfusion injury. The reduced lipid peroxidation and inflammation in the IGL-2 group further underscore its potential in improving liver transplant outcomes. These results highlight the importance of optimizing preservation solutions to enhance the viability and functionality of donor organs, potentially expanding the donor pool and improving the success rates of liver transplantation. Future research should focus on refining preservation techniques and exploring additional protective agents to further improve organ preservation and transplant outcomes. [ABSTRACT FROM AUTHOR]

The reduction of oxidative stress is suggested to be one of the main mechanisms to explain the benefits of subnormothermic perfusion against ischemic liver damage. In this study we investigated the early cellular mechanisms induced in isolated rat livers after 15 min perfusion at temperatures ranging from normothermia (37°C) to subnormothermia (26°C and 22°C). Subnormothermic perfusion was found to maintain hepatic viability. Perfusion at 22°C raised reduced glutathione levels and the activity of glutathione reductase; however, lipid and protein oxidation still occurred as determined by malondialdehyde, 4-hydroxynonenal-protein adducts, and advanced oxidation protein products. In livers perfused at 22°C the lysosomal and ubiquitin proteasome system (UPS) were both activated. The 26S chymotrypsin-like (β5) proteasome activity was significantly increased in the 26°C (46%) and 22°C (42%) groups. The increased proteasome activity may be due to increased Rpt6 Ser120 phosphorylation, which is known to enhance 26S proteasome activity. Together, our results indicate that the early events produced by subnormothermic perfusion in the liver can induce oxidative stress concomitantly with antioxidant glutathione preservation and enhanced function of the lysosomal and UPS systems. Thus, a brief hypothermia could trigger antioxidant mechanisms and may be functioning as a preconditioning stimulus.

Although clinical hypothermia is used for reducing postischemic damage, injurious effects have also been reported. To determine whether hypoxia and oxidative stress are induced by systemic deep hypothermia, we used an in vivo rat model keeping the arterial [[PCO.sub.2] constant. Animals were divided into 4 groups: sham, 2 h deep hypothermia (21°C), 1 h posthypothermia (rewarmed to 37°C after 2 h deep hypothermia), and 3 h normothermia. Blood gases, portal vein blood flow, arterial pressure, and heart rate were monitored throughout the experiment. Liver enzyme antioxidant activity was also examined. The hemodynamic parameters decreased drastically during hypothermia, but were fully restored after rewarming. No changes in hepatic antioxidant activity (catalase, glutathione peroxidase, and superoxide dismutase) were observed. The redox level in liver (GSH/GSSG ratio) was preserved in hypothermia but decreased when animals were rewarmed. ALT did not increase and no evidence of tissue hypoxia was detected in liver regarding the restricted flow during hypothermia. With the described protocol, deep hypothermia is regarded as an experimental safe model. Key words: acid-base, glutathione, hypothermia, lactate, portal flow. L'hypothermie est utilisee en clinique pour diminuer les lesions postischemiques, mais des etudes ont indique qu'elle pouvait aussi avoir des effets nefastes. Pour determiner si une hypothermie systemique profonde induit une hypoxie et un stress oxydatif, nous avons utilise un modele de rats in vivo maintenant une [PCO.sub.2] arterielle constante. Nous avons divise les animaux en quatre groupes : operes de maniere fictive, soumis a une hypothermie profonde pendant 2 heures (21 [degre]C), soumis a une posthypothermie pendant 1 heure (rechauffes a 37[degre]C) et soumis a une normothermie pendant 3 heures. Nous avons mesure les gaz sanguins, le debit de la veine porte, la pression arterielle et la frequence cardiaque pendant toute la duree de l'experience. Nous avons aussi examine l'activite antioxydante hepatique. Les parametres hemodynamiques ont diminue de maniere radicale durant l'hypothermie, mais ont ete totalement retablis apres le rechauffement. Les activites antioxydantes (catalase, glutathion peroxydase et superoxyde dismutase) sont demeurees stables. Le niveau redox dans le foie (rapport GSH/GSSG) a ete preserve durant l'hypothermie, mais a diminue lorsque les animaux ont ete rechauffes. Le taux d'ALT n'a pas augmente et aucun signe d'hypoxie tissulaire n'a ete detecte dans le foie relativement a la diminution du debit durant l'hypothermie. Ce protocole permet de considerer l'hypothermie profonde comme un modele experimental securitaire. Mots-cles : base acide, glutathion, hypothermie, lactate, debit porte. [Traduit par la Redaction], Introduction The process of deep hypothermia, in which body temperature ranges from 15°C to 24°C (Gamez et al. 2008), is associated with a serious perturbation of oxygen delivery (Aardal et [...]