Dataset Information

Anti-fibrotic role and mechanism of Periplaneta americana extracts in CCl4-induced hepatic fibrosis in rats.

ABSTRACT: Hepatic fibrosis is resulted from sustained wound-healing responses to various harmful stimuli, including viral infection, drug toxicity, alcohol, and autoimmune hepatopathy, and it has recently attracted the attention of an increasing number of researchers and clinical workers. The aims of this study were to examine the anti-fibrotic effects of extracts of Periplaneta americana (EPA) on CCl4-induced hepatic fibrosis in rats, to preliminary determine the anti-fibrotic efficacy of EPA, and to identify a potential and effective therapeutic agent to attenuate hepatic fibrosis. In this study, we routinely detected liver functional indices, such as alanine aminotransferase (ALT), aspartate transaminase (AST), and albumin (Alb). We also measured hepatic fibrosis-related serum markers, including hyaluronic acid (HA), laminin (LN), type III procollagen (PC III), and type IV collagen (IV-C) via radioimmunoassay. Moreover, we examined histological activity and fibrosis stage via light microscopy after hematoxylin and eosin and Masson staining. Furthermore, we detected the expressions of nuclear factor-kappa B (NF-κB), alpha-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and tissue inhibitor of metalloprotease-1 (TIMP-1) in rat liver tissues by immunohistochemical staining. We found that EPA, whose main components are viscous sugar amino acids, can reduce the levels hepatic fibrosis-related factors, including HA, LN, PC III, and IV-C, improve liver function, attenuate, or reverse pathological damage associated with hepatic fibrosis, and thus inhibit the progression of hepatic fibrosis. The mechanism of EPA action may be related to the inhibition of TGF-β1, NF-κB, and α-SMA expressions and the reduction of TIMP-1 levels in the liver to reduce the accumulation of extracellular matrix (ECM) components, thereby blocking the relevant signaling pathways and preventing inflammatory responses to attenuate or reverse hepatic fibrosis. EPA may thus be used as a potentially effective therapeutic agent for the treatment of hepatic fibrosis.

SUBMITTER: Li D

PROVIDER: S-EPMC5946930 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Among the various consequence arising from lung injury, hepatic fibrosis is the most severe. Decreasing the effects of hepatic fibrosis remains one of the primary therapeutic challenges in hepatology. Dysfunction of hepatic sinusoidal endothelial cells is considered to be one of the initial events that occur in liver injury. Vascular endothelial growth factor signaling is involved in the progression of genotype changes. The aim of the present study was to determine the effect of the tyrosine kinase inhibitor, vatalanib, on hepatic fibrosis and hepatic sinusoidal capillarization in a carbon tetrachloride (CCl4)‑induced mouse model of liver fibrosis. Liver fibrosis was induced in BALB/c mice using CCl4 by intraperitoneal injection for 6 weeks. The four experimental groups included a control, and three experimental groups involving administration of CCl4, vatalanib and a combination of the two. Histopathological staining and measuring live hydroxyproline content evaluated the extent of liver fibrosis. The expression of α‑smooth muscle actin (SMA) and cluster of differentiation (CD) 34 was detected by immunohistochemistry. Collagen type I, α‑SMA, transforming growth factor (TGF)‑β1 and vascular endothelial growth factor receptor (VEGFR) expression levels were measured by reverse transcription-quantitative polymerase chain reaction (RT‑qPCR). The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy. Liver fibrosis scores and hydroxyproline content were decreased in both vatalanib groups. In addition, both doses of vatalanib decreased mRNA expression levels of hepatic α-SMA, TGF-β1, collagen‑1, VEGFR1, and VEGFR2. Levels of α‑SMA and CD34 protein were decreased in the vatalanib group compared with the CCl4 group. There were significant differences in the number of fenestrae per sinusoid between the groups. The present study identified that administration of vatalanib was associated with decreased liver fibrosis and hepatic sinusoidal capillarization in CCl4-induced mouse models, and is a potential compound for counteracting liver fibrosis.

Project description:Successful recovery from hepatectomy is partially contingent upon the rate of residual liver regeneration. The traditional Chinese medicines known as Periplaneta americana extracts (PAEs) positively influence wound healing by promoting tissue repair. However, the effect of PAEs on liver regeneration is unknown. We used a mouse liver regeneration model after 70% partial hepatectomy (PH) and a hepatocyte culture to determine whether PAEs can promote liver regeneration as effectively as skin regeneration and establish their modes of action. L02 cells were divided into serum-starved control (NC) and three PAEs (serum starvation + 0.1 mg/ml, 0.5 mg/ml, or 1 mg/ml PAEs) groups. L02 cell proliferation was assessed at 24 h, 48 h, and 72 h by CCK-8 assay. Forty male C57 mice were randomly divided into control (NC), normal saline (NS), PAEs400 (400 mg/kg/d), and PAEs800 (800 mg/kg/d) groups (n = 10 per group). The NS and both PAEs groups were administered normal saline and PAEs, respectively, by gavage for 10 days. Two hours after the tenth gavage, the NS and both PAEs groups were subjected to 70% PH and the residual liver was harvested after 48 h. The hepatic regeneration rate was evaluated and hepatocyte proliferation was estimated by immunohistochemical (IHC) staining for Ki-67. Twelve DEG libraries (three samples per group) were prepared and sequencing was performed in an Illumina HiSeq 2000 (Mus_musculus) at the Beijing Genomics Institute. The genes expressed in the liver tissues and their expression profiles were analyzed by bioinformatics. KEGG was used to annotate, enrich, and analyze the pathways. PAEs promoted hepatocyte proliferation in vitro and in vivo and accelerated mouse liver regeneration after 70% PH. The screening criteria were fold change (FC) ≥ 2 and q-value < 0.001. We identified 1,092 known DEGs in PAEs400 and PAEs800. Of these, 153 were categorized in cellular processes. The KEGG analysis revealed that the aforementioned DEGs participated in several signaling pathways closely associated with cell proliferation including PI3K-Akt, MAPK, Apelin, Wnt, FoxO, mTOR, Ras, VEGF, ErbB, Hippo, and AMPK. It was concluded that PAEs can effectively improve liver regeneration via the synergistic activation of different signaling pathways.

Dataset Information

Anti-fibrotic role and mechanism of Periplaneta americana extracts in CCl4-induced hepatic fibrosis in rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets