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2013, Number 2

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Evid Med Invest Salud 2013; 6 (2)

Protective mechanisms of therapeutic strategies based on PPARγ pharmacological inhibition in steatotic liver transplantation

Casillas-Ramírez A, Jiménez-Castro BM, Massip-Salcedo M, Elías-Miró M, Peralta C

Language: Spanish
References: 23
Page: 47-54
PDF size: 325.84 Kb.


ABSTRACT

Background: Numerous steatotic livers are discarded as unsuitable for transplantation because of their poor tolerance of ischemia-reperfusion. The key role of peroxisome proliferator-activated receptor gamma in the vulnerability of this type of liver to ischemia-reperfusion injury associated with transplantation and the benefits of peroxisome proliferator-activated receptor gamma antagonists under these conditions have been previously reported. However, the mechanisms responsible for such effect are poorly understood. Objective: This study examines whether the benefits of peroxisome proliferator-activated receptor gamma antagonists in steatotic liver transplantation could be explained by the regulation of endoplasmic reticulum stress and oxidative stress. Material and methods: Steatotic livers were transplanted in Zucker rats. The peroxisome proliferator-activated receptor gamma was altered pharmacologically and endoplasmic reticulum stress and oxidative stress markers were measured. Results: Protein expression of endoplasmic reticulum stress markers in steatotic livers subjected to either transplantation without treatment or transplantation with administration of peroxisome proliferator-activated receptor gamma antagonist was at baseline levels. On the other hand, treatment with peroxisome proliferator-activated receptor gamma antagonist significantly reduced lipid peroxidation and nitrotyrosine levels when compared with the trasplantation group without treatment, indicating a reduction in peroxynitrite levels. Conclusions: Our results indicate that strategies based on inhibition of peroxisome proliferator-activated receptor gamma protect steatotic liver grafts against ischemia-reperfusion through a reduction in oxidative stress.


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