Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-alpha, IL-1beta, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated IkappaBalpha and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

Research on rat liver fibrosis stages with tissue dispersion quantitative analysis technique / 中华超声影像学杂志

Objective To explore the application value of tissue dispersion quantitative analysis in rat liver fibrosis stages and provide a reference for clinical non-invasive diagnosis of liver fibrosis.Methods Seventy-two male Wistar rats were randomly divided into experimental group (n =64) and control group (n =8).The experimental groups of rats were gavaged with the volume fraction of 60％ CCl4 olive oil solution to form different stages of liver fibrosis,the control group did wvith normal saline,All the rat underwent tissue dispersion quantitative analysis to obtain 12 elastic parameters,the differences in above parameters were compared among rats with different liver fibrosis stages,then the correlation with pathological stages were analyzed.Results Except for COMP,ASM,CORR,there were significant differences in all parameters among rats of different liver fibrosis (P ＜0.05),which were correlated with pathological stages(P ＜0.05).Among these parameters,％ AREA had the highest correlation coefficient (r =0.891,P =0.001).The ROC curve was made by ％AREA to estimate the fibrosis stage.the area under ROC curve for ％ AREA was 0.914 (≥ the control group + S0),0.963 (≥early liver fibrosis S1 + S2),0.969 (≥middle liver fibrosis S3),0.948 (early cirrhosis S4),respectively.Conclusions The technique of tissue dispersion quantitative analysis has a good evaluation value for liver fibrosis stages,it is able to provide a preliminary reference for clinical non-invasive diagnosis of liver fibrosis.