ABSTRACT
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.
Subject(s)
Animals , Mice , Acetaminophen , Alanine Transaminase , Aspartate Aminotransferases , Blotting, Western , Caspase 3 , Cytokines , Glutathione , Hepatocytes , Injections, Intraperitoneal , Interleukin-6 , L-Lactate Dehydrogenase , Liver , Liver Failure, Acute , Malondialdehyde , Necrosis , Reactive Oxygen Species , RNA, Messenger , Tumor Necrosis Factor-alphaABSTRACT
To study high-frequency ultrasound features and pathological characteristics of medullary thyroid carcinoma [medullary thyroid carcinoma, MTC] with the purpose to improve the diagnostic accuracy of this disease. The clinical data of 20 cases of patients with MTC confirmed by the clinical surgery were retrospectively analyzed. And the highfrequency ultrasound features were analyzed and compared with the pathological characteristics. There were 16 cases with tumor invasion into one side of the thyroid gland; 17 cases with tumor in the middle-upper pole of the thyroid gland. And 8 cases was detected with uneven echo of high frequency ultrasound appearance and pathological manifestations of cystic degeneration to necrosis seen under the light microscope or normal thyroid tissue within part of the lump. 16 cases was tested with even echo of high frequency ultrasound appearance, and tumor cells were formed in the solid and block-like shape under the light microscope. And 18 cases were manifested with low echo, with proliferation of fibrous tissue within the intercellular substance under the light microscope. 18 cases could be seen the calcification points and often amyloid-like content deposited in the intercellular substance seen under the light microscope. In addition, the pathological manifestations of the 8 cases combined with lymph node metastasis were the "lash tumor" of the metastatic lymph nodes and primary tumor. MTC was commonly located in the middle-upper region of the thyroid gland and in one leaf of the thyroid gland, combined with lymph node metastasis. The high frequency ultrasound appearance was the even low-echo tumor in round or quasi-circular shape, with obscure boundary and often combined with rough calcification. High frequency ultrasound could be used as the prior physical diagnostic method for medullary thyroid carcinoma
ABSTRACT
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.