Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

Ramos‐Tovar, Erika; Muriel, Pablo

doi:10.3390/antiox9121279

Cited by 179 publications

(122 citation statements)

References 183 publications

(237 reference statements)

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“…In contrast, inflammatory cells, such as monocytes and lymphocytes, also produce additional ROS after activation. 36 , 37 PPAR-γ is a regulator of cell proliferation and immune responses, and can regulate the expression of related genes and participate in the inflammatory response. It has also been confirmed that PPAR-γ plays a strong role in inhibiting liver fibrosis by cross-talk with inflammatory-related factors, such as NF-κB and AP-1, inhibiting T cell activation and macrophage proliferation and secretion.…”

Section: Mechanisms Underlying Hepatic Fibrosis and Ppar-γmentioning

confidence: 99%

The Agonists of Peroxisome Proliferator-Activated Receptor-γ for Liver Fibrosis

Li¹,

Guo²,

Wu³

2021

DDDT

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Liver fibrosis is a common link in the transformation of acute and chronic liver diseases to cirrhosis. It is of great clinical significance to study the factors associated with the induction of liver fibrosis and elucidate the method of reversal. Peroxisome proliferator-activated receptors (PPARs) are a class of nuclear transcription factors that can be activated by peroxisome proliferators. PPARs play an important role in fibrosis of various organs, especially the liver, by regulating downstream targeted pathways, such as TGF-β, MAPKs, and NF-κB p65. In recent years, the development and screening of PPAR-γ ligands have become a focus of research. The PPAR-γ ligands include synthetic hypolipidemic and antidiabetic drugs. In addition, microRNAs, lncRNAs, circRNAs and nano new drugs have attracted research interest. In this paper, the research progress of PPAR-γ in the pathogenesis and treatment of liver fibrosis was discussed based on the relevant literature in recent years.

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Section: Mechanisms Underlying Hepatic Fibrosis and Ppar-γmentioning

confidence: 99%

The Agonists of Peroxisome Proliferator-Activated Receptor-γ for Liver Fibrosis

Li¹,

Guo²,

Wu³

2021

DDDT

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“…There is an increased interest of using antioxidants for medicinal purposes in the recent years, as it is widely accepted that free radicals play a crucial role in many pathological conditions such as inflammation, cancer, and neurodegenerative disorders [ 55 , 56 , 57 , 58 ]. Moreover, several nonsteroidal anti-inflammatory agents have been reported to act either as inhibitors of free radical production or as radical scavengers [ 59 ].…”

Section: Results and Dicussionmentioning

confidence: 99%

Exploring the 2′-Hydroxy-Chalcone Framework for the Development of Dual Antioxidant and Soybean Lipoxygenase Inhibitory Agents

et al. 2021

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2’-hydroxy-chalcones are naturally occurring compounds with a wide array of bioactivity. In an effort to delineate the structural features that favor antioxidant and lipoxygenase (LOX) inhibitory activity, the design, synthesis, and bioactivity profile of a series of 2’-hydroxy-chalcones bearing diverse substituents on rings A and B, are presented. Among all the synthesized derivatives, chalcone 4b, bearing two hydroxyl substituents on ring B, was found to possess the best combined activity (82.4% DPPH radical scavenging ability, 82.3% inhibition of lipid peroxidation, and satisfactory LOX inhibition value (IC50 = 70 μM). Chalcone 3c, possessing a methoxymethylene substituent on ring A, and three methoxy groups on ring B, exhibited the most promising LOX inhibitory activity (IC50 = 45 μM). A combination of in silico techniques were utilized in an effort to explore the crucial binding characteristics of the most active compound 3c and its analogue 3b, to LOX. Α common H-bond interaction pattern, orienting the hydroxyl and carbonyl groups of the aromatic ring A towards Asp768 and Asn128, respectively, was observed. Regarding the analogue 3c, the bulky (-OMOM) group does not seem to participate in a direct binding, but it induces an orientation capable to form H-bonds between the methoxy groups of the aromatic ring B with Trp130 and Gly247.

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“…The mechanism of oxidative stress promotion of liver diseases involves the activation of stellate cells by the free radicals leading to the synthesis of collagen and the extracellular matrix [34]. These are complications associated with liver diseases such as non-alcoholic fatty liver diseases, fibrosis, and encephalopathy.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of the liver proteome in response to an antioxidant intake in rabbits

Sikiru

Arunachalam

Egena

et al. 2021

Egypt Liver Journal

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Background Antioxidant intakes are one of the most cherished dietary approaches for the management of oxidative stress-induced liver damages. These antioxidants exist as the bioactive compounds present in plants and other natural sources functioning in varieties of ways from acting as direct scavengers of the free radicals to acting as the modifiers of genes and proteins expressions. Chlorella vulgaris is one of such antioxidants; it is a unicellular microalga and a rich source of polyphenols which has been reported for its capacity of reducing oxidative stress by upregulation of antioxidant genes. However, there are scarce reports on its effect on antioxidant protein expressions and functions in the liver. This situation necessitates untargeted proteomic profiling of the liver due to the antioxidant intakes as carried out in this present study. Sixteen laboratory weaner rabbits of 8 weeks old with initial average bodyweight of 1060 ± 29.42 g were randomly divided into two groups (n = 8 per group); the first group served as control while the second served as the treatment group were used for this study. Results After a period of 120 days daily consumption of 500 mg of Chlorella vulgaris biomass per kg bodyweight of the rabbit models, the animals were sacrificed and their livers were harvested followed by protein extraction for the untargeted proteomic profiling using LC-MS/Orbitrap Fusion Tribrid™ peptides quantifier and sequencer. Also, there was an assessment of the oxidative stress biomarkers in the liver and serum of the rabbits. Five-hundred and forty-four (544) proteins were identified out of which 204 were unique to the control, 198 were unique to the treatment group, while 142 were common to both groups of the rabbits. Antioxidant proteins commonly found in both groups were upregulated in the treatment group and were significantly associated with oxidative stress-protective activities. There was a reduction in oxidative stress biomarkers of the supplemented group as indicated by the assessment of the liver malondialdehyde concentrations (p < 0.05), total antioxidant capacities (p < 0.05), and antioxidant enzyme activities (p < 0.05). Similarly, these biomarkers were significantly reduced in the serum of the supplemented rabbits (p < 0.05). Conclusion The study concluded that Chlorella vulgaris is an antioxidant agent that could be suitable for reducing liver oxidative stress damage and it is a potential drug candidate for protecting the liver against oxidative stress damages as revealed in the rabbit models.

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Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

Cited by 179 publications

References 183 publications

The Agonists of Peroxisome Proliferator-Activated Receptor-γ for Liver Fibrosis

The Agonists of Peroxisome Proliferator-Activated Receptor-γ for Liver Fibrosis

Exploring the 2′-Hydroxy-Chalcone Framework for the Development of Dual Antioxidant and Soybean Lipoxygenase Inhibitory Agents

Elucidation of the liver proteome in response to an antioxidant intake in rabbits

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