Protective role of polyethylene glycol 35 against hepatic cold and warm ischemia

Abstract

Steatotic livers are considerably more prone to IRI, in which turn, it is known to impair mitochondrial function. Our working hypothesis lies on the fact that impaired mitochondrial function and reduced protection against oxidative stress are increased risk of complications of hepatic surgery in NAFLD patients. Thus, the main challenges in this field are based on the identification of new pharmacological interventions for enhancing hepatic mitochondrial function and capacity for a better clinical outcome of hepatectomy.

The main objective of this doctoral thesis is evaluating the possible protective role of PEG35 against hepatic cold and warm ischemia using different experimental models, more specifically:

1- Understand the role that PEG35 plays in the IGL solutions. In particular, we analyzed the efficacy of fatty liver cold storage using three solution, IGL-0, IGL-1 and IGL-2 containing 0 g/L, 1g/L and 5 g/L of PEG35, respectively (Study 1).

2- Explore a possible synergetic effect on the mitochondria, where PEG35 could enhance HOPE protection, by using the new IGL-2 solution (Study 2).

3- Highlight the use of PEG35-containing solutions as a key factor for hepatic and mitochondrial protection (Study 3).

4- Investigate the utility of PEG35 pharmacological intervention to decipher the mechanisms underlying PEG35 preconditioning-induced protection against IRI, using a model of hypoxia/reoxygenation injury in human hepatoma cell line (Study 4).