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Eur J Pharm Sci ; 109: 464-471, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28887231

RESUMO

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.


Assuntos
Traumatismo por Reperfusão/tratamento farmacológico , Superóxido Dismutase/administração & dosagem , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Lipossomos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Espectroscopia de Ressonância Magnética , Masculino , Microscopia/métodos , Ratos Wistar , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/uso terapêutico , Fator de Transcrição RelA/metabolismo , gama-Glutamiltransferase/sangue
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