Mesenchymal Stem Cells with Enhanced Bcl-2 Expression Promote Liver Recovery in a Rat Model of Hepatic Cirrhosis

Background/Aims: Previous studies have shown that trolline possesses various forms of pharmacological activity, including antibacterial and antiviral potency. The present paper addressed the putative hepatoprotective effects of trolline. Methods: Rats received 2 ml/kg CCl₄ (mixed 1: 1 in peanut oil) intragastrically twice a week for 8 weeks to induce hepatic fibrosis. The animals were then treated with trolline for additional 4 weeks. Liver pathology and collagen accumulation were observed by hematoxylin-eosin and Masson’s trichrome staining, respectively. Serum transaminase activity and collagen-related indicator level were determined by commercially available kits. NF-κB pathway activation was also examined. Moreover, the effects of trolline on hepatic stellate cell (HSC-T6) apoptosis, mitochondrial membrane potential (MMP), and autophagy were assessed. Results: Trolline significantly alleviated CCl₄-induced liver injury and notably reduced the accumulation of collagen in liver tissues. Trolline treatment also markedly decreased inflammatory cytokines levels by inhibiting the NF-κB pathway. Trolline strongly inhibited HSC-T6 activation and notably induced cell apoptosis by modulating the Bax/Bcl-2 ratio, caspase activity, and MMP. Moreover, trolline significantly inhibited HSC-T6 autophagy, as evidenced by the decrease in the formation of autophagic vacuoles and the number of autophagosomes, by regulating the expression levles of LC3, Beclin-1, P62, Atg 5 and 7. Conclusion: Our study demonstrates that trolline ameliorates liver fibrosis, possibly by inhibiting the NF-κB pathway, promoting HSCs apoptosis and suppressing autophagy.

Section: Discussionsupporting

confidence: 59%

Trolline Ameliorates Liver Fibrosis by Inhibiting the NF-κB Pathway, Promoting HSC Apoptosis and Suppressing Autophagy

Bai¹,

Huang²,

Nie³

et al. 2017

“…Carbon tetrachloride (CCl 4 ) is a well-known hepatotoxin that is widely used to induce experimental liver fibrosis and cirrhosis in rodents [5]. CCl 4 -induced hepatotoxicity is believed to involve two phases.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant and Hepatoprotective Effect of Swertiamarin on Carbon Tetrachloride-Induced Hepatotoxicity via the Nrf2/HO-1 Pathway

et al. 2017

Background/Aims: Swertiamarin (STM), the main bioactive component in Swertia mussotii Franch (Gentianaceae), has been shown to exert hepatoprotective effects on experimental liver injury. However, the effects and exact mechanisms of STM on carbon tetrachloride (CCl₄) causing hepatotoxicity are still unknown. This study investigated the potential protective effects and mechanisms of STM on CCl₄-induced liver injury in rats. Methods: Adult male Sprague-Dawley (SD) rats were exposed to CCl₄ with or without STM co-administration for consecutive eight weeks. Results: STM significantly ameliorated CCl₄-induced increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels and histopathological changes in the liver. Hepatic oxidative stress was repressed by STM, as evidenced by the decrease in malondialdehyde (MDA), with concomitant increase in antioxidase activity (e.g. superoxide dismutase (SOD); glutathione peroxidase (GPx)), glutathione (GSH) level. STM also obviously attenuated inflammatory response in CCl₄-lesioned livers as evidenced by the decrease in inflammatory cytokines/ chemokines (e.g. inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β)). Additionally, STM significantly induced the expression of CYPs, efflux transporters and PDZK1 as compared with the CCl₄ group. Moreover, co-administration of STM with CCl₄ remarkably up-regulated the expression of Nrf2, HO-1 and NQO1 compared with the CCl₄ group. Conclusions: The present study demonstrates that STM exerts a protective effect against CCl₄-induced liver injury and inflammation with its antioxidant effects and induction of hepatic detoxification enzymes and efflux transporters expression, at least in part, via the Nrf2/HO-1 pathway in rats.

“…Here, we used rat liver progenitor cell WB-F344 as LPC cell model and HGF as inducer to simulate the process of LPCs hepatic differentiation [29]. Moreover, the hepatocyte cell trait was characterized in terms of hepatocellular function, hepatocellular morphology, and hepatocyte-specific markers [30].…”

Section: Discussionmentioning

confidence: 99%

Mir-382 Promotes Differentiation of Rat Liver Progenitor Cell WB-F344 by Targeting Ezh2

Zheng

Zhou

et al. 2018

Background/Aims: Liver progenitor cells (LPCs) were considered as a promising hepatocyte source of cell therapy for liver disease due to their self-renewal and differentiation capacities, while little is known about the mechanism of LPC differentiate into hepatocytes. This study aims to explore the effect of miR-382, a member of Dlk1-Dio3 microRNA cluster, during hepatic differentiation from LPCs. Methods: In this study, we used rat liver progenitor cell WB-F344 as LPC cell model and HGF as inducer to simulate the process of LPCs hepatic differentiation, then microRNAs were quantified by qPCR. Next, WB-F344 cell was transfected with miR-382 mimics, then hepatocyte cell trait was characterized by multiple experiments, including that periodic acid schiff staining and cellular uptake and excretion of indocyanine green to evaluate the hepatocellular function, qPCR and Western Blotting analysis to detect the hepatocyte-specific markers (ALB, Ttr, Apo E and AFP) and transmission electron microscopy to observe the hepatocellular morphology. Moreover, Luciferase reporter assay was used to determine whether Ezh2 is the direct target of miR-382. Results: We found that miR-382 increased gradually and was inversely correlated with the potential target, Ezh2, during WB-F344 hepatic differentiation. In addition, functional studies indicated that miR-382 increased the level of hepatocyte-specific genes. Conclusions: This study demonstrates that miR-382 may be a novel regulator of LPCs differentiation by targeting Ezh2.