Metformin Attenuates Ischemia-reperfusion Injury of Fatty Liver in Rats Through Inhibition of the TLR4/NF-κB Axis

Abstract

Background: Donor organs for liver transplantation may often havefatty liver disease, which confers a higher sensitivity to ischemia/reperfusion injury. At present, there is no effective treatment forthe condition. Evidence has suggested that metformin, the first-linemedication for diabetes, has protective effects against many disorders.However, the potential role of metformin in ischemia/reperfusioninjury in fatty liver disease remains unclear.Aims: To examine the effect of metformin treatment duringischemia/reperfusion injury in fatty liver and determine the possiblemechanisms.Study Design: Animal experimentation.Methods: Sprague-Dawley male rats were fed a high-fat diet (520kcal/100 g) for 14 weeks and then were subjected to the orthotopicautologous liver transplantation model. Sections of liver tissue werestained with hematoxylin and eosin to visualize the damage. Bloodand liver samples were used to analyze the related proteins andcomponents involved in the inflammatory signaling pathway.Results: We found that metformin significantly ameliorated theischemia/reperfusion injury of the fatty liver through a reduction inalanine aminotransferase/aspartate aminotransferase concentrationsin the serum and a decrease in dead cells, as shown by the terminaldeoxynucleotidyl transferase-mediated dUTP nick-end labeling assay(p