<p>Carvedilol attenuates carbon tetrachloride-induced liver fibrosis and hepatic sinusoidal capillarization in mice</p>

Abstract

Aim To investigate the effect of carvedilol on liver fibrosis and hepatic sinusoidal capillarization in mice with carbon tetrachloride (CCl 4 )-induced fibrosis. Methods A liver fibrosis mouse model was induced by intraperitoneal CCl 4 injection for 8 weeks. The mice were divided into five experimental groups: the normal group, the oil group, the CCl 4 group, the CCl 4 +carvedilol (5 mg/kg/d) group, and the CCl 4 +carvedilol (10 mg/kg/d) group. The extent of liver fibrosis was evaluated by histopathological staining, and the changes in fenestrations of hepatic sinus endothelial cells were observed by scanning electron microscope (SEM). The expression of α-smooth muscle actin (α-SMA) and vascular endothelial markers was detected by immunohistochemistry and Western blot assays. The effect of carvedilol on cell apoptosis was studied via Terminal deoxynucleotidyl Transferase Mediated dUTP Nick End Labeling (TUNEL) assay, and the serum levels of matrix metalloproteinase-8 (MMP-8), vascular endothelial growth factor (VEGF), and angiopoietin-2 were detected through a Luminex assay. Results Liver fibrosis in CCl 4 -treated mice was attenuated by reduced accumulation of collagen and the reaction of inflammation with carvedilol treatment. Carvedilol reduced the activation of hepatic stellate cells (HSCs) and increased the number of apoptotic cells. The expression of α-SMA, CD31, CD34 and VWF (von Willebrand factor) was significantly decreased after carvedilol treatment. In addition, the number of fenestrae in the hepatic sinusoid showed notable differences between the groups, and the serum levels of MMP-8, VEGF and angiopoietin-2 were increased in the mice with liver fibrosis and reduced by carvedilol treatment. Conclusion The study demonstrated that carvedilol could prevent further development of liver fibrosis and hepatic sinusoidal capillarization in mice with CCl 4 -induced fibrosis.

Protective Effects of Flavone from Tamarix aphylla against CCl4-Induced Liver Injury in Mice Mediated by Suppression of Oxidative Stress, Apoptosis and Angiogenesis

“…Our immunohistochemical staining results showed an increased CD31 protein expression level in CCl 4 model group compared to the control group. This was compatible with the literature where an increase in the expression levels of CD31 was noticed in mice injected with CCl 4 [61,67]. The flavone decreased the elevated expression of CD31 and effectively attenuated liver injury induced by CCl 4 .…”

Doxazosin Attenuates Liver Fibrosis by Inhibiting Autophagy in Hepatic Stellate Cells via Activation of the PI3K/Akt/mTOR Signaling Pathway

“…Our previous studies confirmed that carvedilol, an inhibitor of β1-, β2- and α1-adrenoreceptors, could attenuate carbon tetrachloride (CCl 4 )-induced liver fibrosis and ameliorate intrahepatic angiogenesis and portal pressure. 15 , 16 In addition, we found that carvedilol attenuated fibrosis by suppressing autophagy and inducing apoptosis in HSCs. 17 Autophagy and apoptosis are two catabolic pathways that are vital for organismal homeostasis, especially in the liver, and their dysregulation contributes to liver fibrosis.…”

The endothelial dysfunction blocker CU06-1004 ameliorates choline-deficient L-amino acid diet-induced non-alcoholic steatohepatitis in mice

“…However, capillarized LSECs release inflammatory mediators and contribute to the recruitment of macrophages and HSCs, thus promoting inflammation and fibrosis [ 46 ]. CD31 is a common marker for LSEC capillarization that has been used to assess for increased LSEC capillarization in NASH [ 5 ]. In mice with mild CDAA-induced NASH, treatment with CU06-1004 decreased the expression of CD31, suggesting that it attenuated sinusoidal capillarization.…”

“…Non-alcoholic steatohepatitis (NASH) is an advanced form of NAFLD and typically presents with steatosis, inflammation, and fibrosis in the liver [2]. However, although several studies have tested various treatment approaches for NASH, there is no approved, effective therapy available to date [3][4][5].…”