Our experimental data showed that treatment with ATZ significantly enhanced LPS/D-Gal-induced elevation of serum aspartate transaminase (AST) and alanine transaminase (ALT), exacerbated the hepatic histopathological abnormality and decreased the survival rate of experimental animals. ATZ inhibited the activity of CAT, increased the content of H2O2 and the levels of malondialdehyde

Bortezomib chemical structure (MDA) in liver tissues. In addition, treatment with ATZ also enhanced LPS/D-Gal-induced hepatic apoptosis as evidenced by increased caspases activities in liver tissues and increased number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells in liver sections. These findings suggested that CAT might be involved in the progression of LPS/D-Gal-induced fulminant liver injury. “
“Hepatic ischemia/reperfusion (IRI) injury remains a major challenge in clinical Palbociclib ic50 orthotopic liver transplantation (OLT). Tenascin-C (Tnc) is an extracellular matrix protein (ECM) involved in various aspects of immunity and tissue injury. Using a Tnc-deficient mouse model, we present data that suggest an active role for Tnc in liver IRI. We show that Tnc-deficient mice have a reduction in liver damage and a significant improvement in liver regeneration after IRI. The inability

of Tnc−/− mice to express Tnc significantly reduced the levels of active caspase-3/transferase-mediated dUTP nick end-labeling (TUNEL) apoptotic markers and enhanced the expression of the proliferation cell nuclear antigen (PCNA) after liver IRI. The lack of Tnc expression resulted in impaired leukocyte recruitment and decreased expressions of interleukin (IL)-1β, IL-6, and CXCL2 after liver reperfusion. Tnc-deficient livers were characterized by altered expression patterns of vascular adhesion molecules, such as vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 post-IRI. Moreover, matrix metalloproteinase-9 (MMP-9) synthesis, which

facilitates leukocyte transmigration across vascular barriers in liver IRI, was markedly down-regulated in the absence of Tnc. We also show that Tnc is capable of inducing MMP-9 expression in isolated neutrophils through Toll-like receptor 4. Therefore, our data suggest that Tnc is a relevant mediator of the pathogenic events underlying out liver IRI. The data also support the view that studies aimed at further understanding how newly synthesized ECM molecules, such as Tnc, participate in inflammatory responses are needed to improve therapeutic approaches in liver IRI. (HEPATOLOGY 2011) Hepatic ischemia/reperfusion injury (IRI) occurs during trauma, shock, transplantation, and other surgical procedures where the blood supply to liver is temporarily interrupted. In transplantation, IRI insult can lead to a significantly higher incidence of acute and chronic rejections.