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Eur J Pharm Sci ; 109: 464-471, 2017 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-28887231

RESUMEN

Liver ischaemia-reperfusion injury (IRI) may occur during hepatic surgery and is unavoidable in liver transplantation. Superoxide dismutase enzymosomes (SOD-enzymosomes), liposomes where SOD is at the liposomal surface expressing enzymatic activity in intact form without the need of liposomal disruption, were developed with the aim of having a better insight into its antioxidant therapeutic outcome in IRI. We also aimed at validating magnetic resonance microscopy (MRM) at 7T as a tool to follow IRI. SOD-enzymosomes were characterized and tested in a rat ischaemia-reperfusion model and the therapeutic outcome was compared with conventional long circulating SOD liposomes and free SOD using biochemical liver injury biomarkers, histology and MRM. MRM results correlated with those obtained using classical biochemical biomarkers of liver injury and liver histology. Moreover, MRM images suggested that the therapeutic efficacy of both SOD liposomal formulations used was related to prevention of peripheral biliary ductular damage and disrupted vascular architecture. Therefore, MRM at 7T is a useful technique to follow IRI. SOD-enzymosomes were more effective than conventional liposomes in reducing liver ischaemia-reperfusion injury and this may be due to a short therapeutic window.


Asunto(s)
Daño por Reperfusión/tratamiento farmacológico , Superóxido Dismutasa/administración & dosificación , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Liposomas , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Espectroscopía de Resonancia Magnética , Masculino , Microscopía/métodos , Ratas Wistar , Daño por Reperfusión/sangre , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Superóxido Dismutasa/uso terapéutico , Factor de Transcripción ReIA/metabolismo , gamma-Glutamiltransferasa/sangre
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