Mouse models of metabolic liver injury.

Metabolic liver injury is one of the fastest growing health problems worldwide. Alcoholic and non-alcoholic fatty livers have been shown to be associated with progression to end-stage liver diseases, as well as to liver cancers, in humans. More importantly, there are no validated therapies for these disorders, therefore intensive research is required in this area. This review of standard operation procedures focuses on the experimental models of fatty liver disease in the mouse. Firstly, use of these experimental models might improve understanding of underlying mechanisms, and secondly this might help to test potential therapeutic options. This article includes, besides a short historic background, an insight into the pathobiochemical mechanisms and detailed experimental procedures as well as the practical implementation of these models.

Neutrophil recruitment in the reperfused-injured rat liver was effectively attenuated by repertaxin, a novel allosteric noncompetitive inhibitor of CXCL8 receptors: a therapeutic approach for the treatment of post-ischemic hepatic syndromes.

Hepatic reperfusion injury represents a crucial problem in several clinical situations including liver transplantation, extensive hepatectomy and hypovolemic shock with resuscitation. Repertaxin is a new non-competitive allosteric blocker of interleukin-8 (CXCL8) receptors, which by locking CXCR1/R2 in an inactive conformation, prevents receptor signaling and polymorphonuclear leukocyte (PMN) chemotaxis. The present study shows that repertaxin dramatically prevents rat post-ischemic hepatocellular necrosis (80% of inhibition) and PMN infiltration (96% of inhibition) at a clinically-relevant time (24 h) of reperfusion. Treatment with repertaxin by continuous infusion is demonstrated to be the optimal route of administration of the compound especially in view of its clinical therapeutic use. Because repertaxin has proven to be safe and well tolerated in different animal studies and in phase I studies in human volunteers, it is in fact a candidate novel therapeutic agent for the prevention and treatment of hepatic post-ischemic injury.