scholarly journals Farnesoid X Receptor as Target for Therapies to Treat Cholestasis-Induced Liver Injury

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1846
Author(s):  
Anca D. Petrescu ◽  
Sharon DeMorrow
Keyword(s):  
Bile Flow ◽  
Disease Burden ◽  
Molecular Level ◽  
Farnesoid X Receptor ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Mechanistic Studies ◽  
Liver Injuries ◽  
Anti Oxidant

Recent studies on liver disease burden worldwide estimated that cirrhosis is the 11th most common cause of death globally, and there is a great need for new therapies to limit the progression of liver injuries in the early stages. Cholestasis is caused by accumulation of hydrophobic bile acids (BA) in the liver due to dysfunctional BA efflux or bile flow into the gall bladder. Therefore, strategies to increase detoxification of hydrophobic BA and downregulate genes involved in BA production are largely investigated. Farnesoid X receptor (FXR) has a central role in BA homeostasis and recent publications revealed that changes in autophagy due to BA-induced reactive oxygen species and increased anti-oxidant response via nuclear factor E2-related factor 2 (NRF2), result in dysregulation of FXR signaling. Several mechanistic studies have identified new dysfunctions of the cholestatic liver at cellular and molecular level, opening new venues for developing more performant therapies.

Trilobatin Protects Cardiomyocytes from Hypoxia/ Reperfusion Injury by Regulating the Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 133-138
Author(s):  
Wenyu Chen ◽  
Hui He
Keyword(s):  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Cellular Injury ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
H9c2 Cells ◽  
Natural Plant ◽  
Induced Changes

Trilobatin is a natural plant-derived glycosylated flavonoid that has been shown to exhibit multiple beneficial pharmacologic activities including protection of heart against H/R-induced cardiomyocyte injury. However, the molecular mechanisms underlying protection from H/R-induced cardiomyocyte injury remain unknown. Using H9C2 cells as a model, we examined the effect of trilobatin on H/R-induced cellular injury, apoptosis, and generation of reactive oxygen species. The results showed that trilobatin protected H9C2 cells not only from cell death and apoptosis, but also counteracted H/R-induced changes in malondialdehyde, superoxide dismutase, glutathione, and glutathione peroxidase. The evaluation of the mechanism underlying the effect of trilobatin on protection from H/R-induced cellular injury suggested changes in the regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.

scholarly journals The Potential of Lactobacillus spp. for Modulating Oxidative Stress in the Gastrointestinal Tract

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 610 ◽  
Author(s):  
Yanzhuo Kong ◽  
Kenneth J. Olejar ◽  
Stephen L. W. On ◽  
Venkata Chelikani
Keyword(s):  
Oxidative Stress ◽  
Nuclear Factor Kappa B ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Mechanisms Of Action ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Pathogenic Microorganisms ◽  
Gi Tract ◽  
Lactobacillus Spp

The gastrointestinal (GI) tract is crucial for food digestion and nutrient absorption in humans. However, the GI tract is usually challenged with oxidative stress that can be induced by various factors, such as exogenous pathogenic microorganisms and dietary alterations. As a part of gut microbiota, Lactobacillus spp. play an important role in modulating oxidative stress in cells and tissues, especially in the GI tract. Oxidative stress is linked with excessive reactive oxygen species (ROS) that can be formed by a few enzymes, such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs). The redox mechanisms of Lactobacillus spp. may contribute to the downregulation of these ROS-forming enzymes. In addition, nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf-2) and nuclear factor kappa B (NF-κB) are two common transcription factors, through which Lactobacillus spp. modulate oxidative stress as well. As oxidative stress is closely associated with inflammation and certain diseases, Lactobacillus spp. could potentially be applied for early treatment and amelioration of these diseases, either individually or together with prebiotics. However, further research is required for revealing their mechanisms of action as well as their extensive application in the future.

Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2

2018 ◽  
Vol 46 (02) ◽  
pp. 469-488 ◽  
Author(s):  
Ji Yun Jung ◽  
Sang Mi Park ◽  
Hae Li Ko ◽  
Jong Rok Lee ◽  
Chung A Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Caspase 3 ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation ◽  
Anti Oxidant

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100[Formula: see text][Formula: see text]g/mL) significantly inhibited AA[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA[Formula: see text][Formula: see text][Formula: see text]iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA[Formula: see text][Formula: see text][Formula: see text]iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300[Formula: see text]mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.

scholarly journals NRF2 Regulation by Noncoding RNAs in Cancers: The Present Knowledge and the Way Forward

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3621
Author(s):  
Federico Pio Fabrizio ◽  
Angelo Sparaneo ◽  
Lucia Anna Muscarella
Keyword(s):  
Noncoding Rna ◽  
Gene Network ◽  
Noncoding Rnas ◽  
Antioxidant Response ◽  
Present Knowledge ◽  
Cellular Damage ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Cellular Mechanisms

Nuclear factor erythroid 2-related factor 2 (NRF2) is the key transcription factor triggered by oxidative stress that moves in cells of the antioxidant response element (ARE)-antioxidant gene network against reactive oxygen species (ROS) cellular damage. In tumors, the NRF2 pathway represents one of the most intriguing pathways that promotes chemo- and radioresistance of neoplastic cells and its activity is regulated by genetic and epigenetic mechanisms; some of these being poorly investigated in cancer. The noncoding RNA (ncRNA) network is governed by microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) and modulates a variety of cellular mechanisms linked to cancer onset and progression, both at transcriptional and post-transcriptional levels. In recent years, the scientific findings about the effects of ncRNA landscape variations on NRF2 machines are rapidly increasing and need to be continuously updated. Here, we review the latest knowledge about the link between NRF2 and ncRNA networks in cancer, thus focusing on their potential translational significance as key tumor biomarkers.

Spermatogenic Apoptosis and the Involvement of the Nrf2 Pathway in Male Mice Following Exposure to Nano Titanium Dioxide

2020 ◽  
Vol 16 (3) ◽  
pp. 373-381
Author(s):  
Fashui Hong ◽  
Yingjun Zhou
Keyword(s):  
Titanium Dioxide ◽  
Target Gene ◽  
Titanium Dioxide Nanoparticles ◽  
Reproductive Toxicity ◽  
Peroxidation Of Lipids ◽  
Related Factor ◽  
Nuclear Factor ◽  
Gene Products ◽  
Oxygen Species ◽  
Nano Titanium Dioxide

Titanium dioxide nanoparticles (TiO2 NPs) are largely manufactured and extensively applied for the treatment of environmental pollution. Studies have proved that exposure to TiO2 NPs leads to toxicity of the reproductive system. However, very few studies have highlighted the involvement of nuclear factor erythroid-2 related factor 2 (Nrf2) under TiO2 NPinduced spermatogenic apoptosis. Our findings suggested that TiO2 NPs could cross the blood–testis barrier and were aggregated or deposed in spermatogenic cells, which resulted in spermatogenic apoptosis. Furthermore, exposure to TiO2 NPs caused an overproduction of reactive oxygen species and the peroxidation of lipids, proteins, and DNA. Such exposure also caused significant decreases in the activities of SOD, GSH–PX, GST, and GSH content in the testis. Importantly, exposure to TiO2 NPs resulted in an up-regulation of Keap1 expression and a down-regulation of Nrf2 and its target gene products, NQO1, HO-1, GCLC, PKC, and PI3K. The present study implies that TiO2 NPs could lead to spermatogenic apoptosis, and Nrf2 is the initial factor that responded to such reproductive toxicity by regulating the expression of antioxidative proteins.

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