Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration  in liver fibrosis animal model

Sadyah, Nur Anna Chalimah; Putra, Agung; Dirja, Bayu Tirta; Hidayah, Nurul; Azzahara, Salma Yasmine; Irawan, Risky Candra Satria

doi:10.18051/univmed.2021.v40.29-35

Cited by 4 publications

(5 citation statements)

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“…CCl4 is metabolized by the mitochondrial monooxygenase system (cytochrome P450 2E1) to its active metabolite, an unstable trichloromethyl (CCl3) free radical, and then this active metabolite immediately transforms into trichloromethyl peroxyl (CCl3O2). (17,29,30) These free radicals damage the cell membrane via peroxidative degradation of the fatty acids from phospholipids of the cell membrane and endoplasmic reticulum. (3,5) Subsequently, this process results in the fragmentation of the lipid peroxide radicals, lipid hydroperoxides, and other products, each acting as an active oxidizing agent.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective activity of Averrhoa bilimbi L. fruit extract on carbon tetrachloride-induced acute liver faiure in Wistar rats

et al. 2023

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Background Acute liver failure (ALF) is a state of rapid and progressive deterioration of liver function. Continuous exposure to chemicals and viruses can increase reactive oxygen species (ROS) which leads to prolonged inflammation due to the production of tumor necrosis factor-alpha (TNF-á) thus inhibiting the production of platelet-derived growth factor (PDGF). The objective of this study was to evaluate the effect of administration of Averrhoa bilimbi L. fruit extract on PDGF levels and TNF-á levels in carbon tetrachloride (CCl4)-induced ALF rats. MethodsThis study used a post-test-only control group design involving 20 Wistar rats. They were randomized into 4 groups, namely sham, control, T1, and T2. Group T1 was exposed to CCl4 with the administration of A. bilimbi fruit extract at a dose of 500mg/kgBW, while, group T2 was exposed to CCl4 and given A. bilimbi fruit extract of 750 mg/kgBW. On the 15th day, the serum was analyzed to determine the levels of PDGF and TNF-á using ELISA. ResultsThe highest mean PDGF level in the control group was 146.60±15.36 pg/mL, while the highest mean TNF-á level in group T1 was 40.11±4.44 pg/mL. The One-way ANOVA test showed that there were significant differences in TNF-á (p=0.002) and PDGF (p=0.000) levels between the study groups. ConclusionThe administration of A.bilimbi L. fruit extract affected PDGF and TNF-á levels in CCl4-induced ALF rats. The present study revealed that A. bilimbi fruits have significant hepatoprotective activity in experimental Wistar rats.

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Section: Discussionmentioning

confidence: 99%

Hepatoprotective activity of Averrhoa bilimbi L. fruit extract on carbon tetrachloride-induced acute liver faiure in Wistar rats

et al. 2023

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“…Protection against fibrogenesis was showed via Treg depletion, which resulted in increased IL-6 production and a reduction in IL-10 by effector T cells in the intrahepatic environment, leading to exacerbated fibrosis [173]. While the precise T cell subset for cytokine production was not defined, the importance of IL-10 production against liver fibrogenesis has been described, suggesting an antagonistic role against TGF-β [137, [174][175][176], supporting the deductions stated earlier regarding protective IL-10producing Tregs. In agreement with this, a similar BDL cholestasis model demonstrated expanded FoxP3+ Tregs in response to injury and suppression of pro-fibrogenic CD8+ Tc cell and Th17 cell activity, conforming with the severity of fibrosis after Treg ablation.…”

Section: Potential Role Of Tregs In the Attenuation Of Liver Fibrosismentioning

confidence: 99%

Inflammatory Network of Liver Fibrosis and How It Can Be Targeted Therapeutically

Lowe,

Tanase,

Maghami

et al. 2023

Immuno

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Liver fibrosis is a complex, dynamic process associated with a broad spectrum of chronic liver diseases and acute liver failure, characterised by the dysregulated intrahepatic production of extracellular matrix proteins replacing functional liver cells with scar tissue. Fibrosis progresses due to an interrelated cycle of hepatocellular injury, triggering a persistent wound-healing response. The accumulation of scar tissue and chronic inflammation can eventually lead to cirrhosis and hepatocellular carcinoma. Currently, no therapies exist to directly treat or reverse liver fibrosis; hence, it remains a substantial global disease burden. A better understanding of the intricate inflammatory network that drives the initiation and maintenance of liver fibrosis to enable the rationale design of new intervention strategies is required. This review clarifies the most current understanding of the hepatic fibrosis cellular network with a focus on the role of regulatory T cells, and a possible trajectory for T cell immunotherapy in fibrosis treatment. Despite good progress in elucidating the role of the immune system in liver fibrosis, future work to better define the function of different immune cells and their mediators at different fibrotic stages is needed, which will enhance the development of new therapies.

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“…Nrf2 has been reported able to increase SMAD7 expression, a negative regulator of TGF-β, by decreasing the expression of transformation growth factor beta receptor-1 (TGF-βRI). Inhibition of the TGF-β pathway through the activation of SMAD7 by Nrf2 has been shown to reduce the incidence of liver fibrosis [37], [50]. However, low Nrf2 has been found in increased HSC activation which is characterized by an increase in alpha-smooth muscle actin (α-SMA), Collagen type I, and IV [49].…”

Section: Nuclear Factor Erythroid 2-related Factor 2 Inhibit Hepatic ...mentioning

confidence: 99%

Nuclear Factor Erythroid 2-Related Factor 2 Versus Reactive Oxygen Species: Potential Therapeutic Approach on Fighting Liver Fibrosis

Setiawati

Liem

Husna

2023

Open Access Maced J Med Sci

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Chronic liver disease (CLD) is a progressive deterioration of the liver due to exposure to viruses, drugs, fat accumulation, and toxicity which lead to an imbalance between extracellular matrix accumulation and degradation. Accumulation of the extracellular matrix is a normal liver response at the beginning of the injury. However, increasing extracellular matrix accumulation leads to fibrosis, cirrhosis, and organ failure. Until today, liver transplant is the gold standard therapy for end-stage CLD. Unfortunately, the liver transplant itself faces difficulties such as finding a compatible donor and dealing with complications after treatment. This review provides further information about nuclear factor erythroid 2-related factor 2 (Nrf2) as an alternative approach to fight liver fibrosis. Transformation of hepatic stellate cell (HSC) to myofibroblast has been known as the main mechanism that occurs in fibrosis while epithelial-mesenchymal transition (EMT) and mitochondrial dysfunction become the mechanism followed. In these conditions, oxidative stress is the great promoter which builds a vicious cycle leading to CLD progressivity. Hence, Nrf2 as antioxidant regulator becomes the potential target to break the cycle. While reactive oxygen species (ROS) in oxidative stress induce HSC activation, EMT, and mitochondrial dysfunction through activation of many signaling pathways, Nrf2 acts to diminish ROS directly by regulating secreted antioxidants and its scavenging action. Nrf2 also inactivates fibrosis signaling pathways and plays a role in maintaining mitochondrial health. Therefore, Nrf2 can be a potential target for liver fibrosis therapy.

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Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model

Cited by 4 publications

References 30 publications

Hepatoprotective activity of Averrhoa bilimbi L. fruit extract on carbon tetrachloride-induced acute liver faiure in Wistar rats

Hepatoprotective activity of Averrhoa bilimbi L. fruit extract on carbon tetrachloride-induced acute liver faiure in Wistar rats

Inflammatory Network of Liver Fibrosis and How It Can Be Targeted Therapeutically

Nuclear Factor Erythroid 2-Related Factor 2 Versus Reactive Oxygen Species: Potential Therapeutic Approach on Fighting Liver Fibrosis

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