Assessment of the possible roles of SB-269970  versus  ketanserin on carbon tetrachloride-induced liver fibrosis in rats: Oxidative stress/TGF-β 1 -induced HSCs activation pathway

Atallah, Marwa Ahmed Amin; Elaidy, Samah M.; Tawfik, Mona K.

doi:10.1016/j.pharep.2017.11.017

Cited by 10 publications

(6 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Saeid et al treated thermal-injured mice with a 5HTR 2A/2C antagonist (Ketanserin) and found that it could promote anti-fibrotic effects by regulating the phenotype of macrophages [ 77 ]. A study by Atallah et al showed that blocking 5-HTR 2A with Ketanserin or 5-HTR 7 with SB-269970 reduced oxidative stress/TGF-β1-induced liver fibrosis in CCl4-challenged rats [ 78 ], which were consistent with those reported by Dalia et al [ 79 ]. Liang and Shan conducted in vivo and in vitro experiments showing that hyperglycemia or type 2 diabetes can upregulate the expression of 5-HTR 2A , the synthetic enzyme for 5-HT, and MAO-A, leading to increased intracellular 5-HT levels, mitochondrial reactive oxygen species (ROS) generation, and myofibroblastization of HSCs.…”

Section: -Ht In Cirrhosissupporting

confidence: 85%

The janus face of serotonin: Regenerative promoter and chronic liver disease aggravator

Mao,

Liu,

Zhu

et al. 2024

Heliyon

View full text Add to dashboard Cite

Section: -Ht In Cirrhosissupporting

confidence: 85%

The janus face of serotonin: Regenerative promoter and chronic liver disease aggravator

Mao,

Liu,

Zhu

et al. 2024

Heliyon

View full text Add to dashboard Cite

“…Serotonin is also known to have numerous functions, such as smooth muscle contraction of blood vessels and bronchi, acceleration of peristaltic movement (Berger et al, 2009), respiratory rhythm (Cinelli et al, 2020), regulation of β cells in the pancreas (Berger et al, 2009;Li et al, 2000), liver regeneration (Inoue et al, 2018;Kamimura et al, 2018), liver fibrosis (Kyritsi et al, 2020), protection against intestinal ischemia (Tackett et al, 2019) and food-seeking behavior (He et al, 2020), and its reuptake inhibitors are used as an antidepressant in relation to gastrointestinal symptoms (Salisbury et al, 2020). In addition, serotonin is reportedly involved in the fibrosis of NAFLD (Atallah et al, 2018), the modification of lipid metabolisms (Namkung et al, 2018), the activation of signal from serotonin receptor on the hepatocytes (Choi et al, 2018), and the modulation of autophagy and Notch signal (Martin et al, 2020). Interestingly, Haub et al (2011) reported that the blockade of the serotonin receptor HTR3, which is the receptor expressed in the intestine, modified the strength of the tight junction and improved the obesity-associated fatty liver in mice.…”

Section: Discussionmentioning

confidence: 99%

Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver

Kamimura

Owaki

et al. 2021

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD.This article has an associated First Person interview with the first author of the paper.

show abstract

“…Hepatic fibrosis is characterized by HSC oxidative stress, which may lead to an imbalance in ECM synthesis and degradation and transform HSCs into proliferative myofibroblasts (Kumar et al, 2016; Perepelyuk et al, 2013). One important pathogenic mechanism of HSC activation is oxidative stress, which results in overexpression of various inflammatory cytokines, ultimately resulting in hepatic fibrosis (Atallah et al, 2017; Yin et al, 2013). Chen et al found that EGCG significantly inhibited HSC growth and activation by inducing cell cycle arrest and apoptosis, blocking TGF‐β signal transduction, and inhibiting the gene expression levels of COL1A1 , fibronectin, and α‐SMA (Chen et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of epigallocatechin‐3‐o‐gallate combined with organic selenium against transforming growth factor‐beta 1‐induced fibrosis in LX ‐2 cells

Zhang

Yuan

et al. 2022

Journal of Food Biochemistry

View full text Add to dashboard Cite

In this study, we investigated the protective effects and possible mechanism of epigallocatechin‐3‐o‐gallate (EGCG) combined with organic selenium in transforming growth factor (TGF)‐β1‐activated LX‐2 cells. After 12 h of starvation, LX‐2 cells were treated with 10 ng/ml of recombinant TGF‐β1 and different concentrations of EGCG, L‐selenomethionine (L‐SeMet), or L‐selenomethylcysteine (L‐SeMC) for 24 h. We found that 100 and 200 μM EGCG combined with 1 mM L‐SeMet or L‐SeMC showed a synergistic effect in decreasing the survival rate of activated LX‐2 cells. In addition, the combination of 100 mM EGCG and 1 mM L‐SeMet or L‐SeMC promoted the apoptosis of activated LX‐2 cells. Compared with the EGCG treatment group, the combination intervention group had significantly suppressed levels of hepatic stellate cell activation markers including alpha‐smooth muscle actin, collagen type I alpha 1, collagen type III alpha 1, 5‐hydroxytryptophan (5‐HT), and 5‐HT receptors 2A and 2B. Moreover, interleukin‐10 levels were decreased, while TGF‐β1 levels were increased after TGF‐β1 activation in LX‐2 culture medium, whereas the combin1ation intervention reversed this phenomenon. The combination treatment had a more pronounced effect than any single treatment at the same dose. These results demonstrated that the combination of EGCG and organic selenium synergistically improves the TGF‐β1‐induced fibrosis of LX‐2 cells to some extent by promoting apoptosis and inhibiting cell activation. Practical applications Here, we found that the effects of epigallocatechin‐3‐o‐gallate (EGCG) + L‐selenomethionine or L‐selenomethylcysteine were more pronounced than those of EGCG alone. Future studies should investigate the protective effects of green tea and selenium‐enriched green tea against hepatic fibrosis and explore the differences in their molecular mechanisms. The results of this study will be helpful for the development and utilization of selenium‐enriched tea for food processing and health supplement production.

show abstract

Assessment of the possible roles of SB-269970 versus ketanserin on carbon tetrachloride-induced liver fibrosis in rats: Oxidative stress/TGF-β 1 -induced HSCs activation pathway

Abstract: Blockade of 5-HT2A and 7 receptors each alone could be a future reliable therapeutic approach in liver fibrosis through a reduction in oxidative stress/TGF-β-induced HSCs activation pathway.

Cited by 10 publications

References 56 publications

The janus face of serotonin: Regenerative promoter and chronic liver disease aggravator

The janus face of serotonin: Regenerative promoter and chronic liver disease aggravator

Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver

Protective effects of epigallocatechin‐3‐o‐gallate combined with organic selenium against transforming growth factor‐beta 1‐induced fibrosis in LX ‐2 cells

Contact Info

Product

Resources

About