Nrf2/ARE axis signalling in hepatocyte cellular death

Ghanim, Bayan Y.; Qinna, Nidal A.

doi:10.1007/s11033-022-07125-6

Cited by 14 publications

(10 citation statements)

References 90 publications

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“…Knowledge regarding the antioxidant effects of irisin is very recent and new. Current findings are in line with a few studies that were suggestive of its antioxidant properties and beneficial outcomes in the redox system, specifically on the NRF2/HMGB1 axis, which is a key modulator of a cascade of antioxidant molecules [ 12 , 13 , 14 ]. Therefore, it could be concluded that interventional exogenous irisin can induce the same effect as exercise on skeletal muscles and increase the gene expression of several antioxidant proteins, including Cu/Zn superoxide dismutase (SOD1), manganese-dependent superoxide dismutase (SOD2), catalase, glutathione peroxidase 1 (GPX1), glutathione S-transferases (GSTs), and NADPH oxidase 4 (NOX4).…”

Section: Discussionsupporting

confidence: 88%

Impact of Sustained Exogenous Irisin Myokine Administration on Muscle and Myocyte Integrity in Sprague Dawley Rats

et al. 2022

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Irisin is an exercise-induced myokine implicated as a fundamental mediator of physical activity benefits. The aim of the present study was to investigate the role of the chronic administration model of irisin on the physiological and molecular status of skeletal muscle. A total of 20 female Sprague Dawley rats (250 ± 40 g) were implanted with an irisin-loaded osmotic pump (5 µg/kg/day) for 42 days; in addition, 3 females received a single subcutaneous injection of irisin (5 µg/kg). On a weekly basis for six weeks, animals were weighed and blood samples were collected. After 42 days, hind muscle biopsies were collected for histology and gene analysis. Serum irisin, clinical biochemistry, and histopathology were quantified and evaluated. Genes encoding for different physiological muscle activities, such as oxidative stress, fatty acid metabolism, muscle hypertrophy, mitochondrial fusion, and aging were assayed. The results showed a significant reduction in body weight percentage and creatine kinase level without affecting the morphological characteristics of skeletal muscle. Significant changes were noted in genes involved in muscle physiological activity, growth, and aging, as well as genes encoding for the antioxidant system, fatty acid oxidation processes, and mitochondrial fusion. In conclusion, exogenous irisin can induce the same physiological and molecular mechanisms that might be induced by exercise.

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Section: Discussionsupporting

confidence: 88%

Impact of Sustained Exogenous Irisin Myokine Administration on Muscle and Myocyte Integrity in Sprague Dawley Rats

et al. 2022

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“…Nrf2 has been confirmed with the function on promotion of liver regeneration and inhibition of hepatocyte apoptosis ( Chan et al, 2021 ; Ghanim and Qinna 2022 ). Therefore, we explored the effect of MCGP on liver regeneration and apoptosis.…”

Section: Resultsmentioning

confidence: 89%

“…On the other hand, the restoration of liver normal function after acute liver injury can be acquired through promoting liver regeneration, which is proved to be efficient in APAP- or CCl 4 -induced liver injury ( Yan et al, 2018 ; Humpton et al, 2021 ). In addition, activation of Nrf2 enhances functional liver regeneration ( Chan et al, 2021 ; Ghanim and Qinna 2022 ). Hence, we supposed that MCGP could also promote liver regeneration through the activation of the Nrf2 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Methyl 6-O-cinnamoyl-α-d-glucopyranoside Ameliorates Acute Liver Injury by Inhibiting Oxidative Stress Through the Activation of Nrf2 Signaling Pathway

Deng

Jun

et al. 2022

Front. Pharmacol.

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Excessive stimulation of hepatotoxins and drugs often lead to acute liver injury, while treatment strategies for acute liver injury have been limited. Methyl 6-O-cinnamoyl-α-d-glucopyranoside (MCGP) is a structure modified compound from cinnamic acid, a key chemical found in plants with significant antioxidant, anti-inflammatory, and antidiabetic effects. In this study, we investigated the effects and underlying mechanisms of MCGP on acetaminophen (APAP)- or carbon tetrachloride (CCl4)-induced acute liver injury. As a result, MCGP inhibited cell death and apoptosis induced by APAP or CCl4, and suppressed the reactive oxygen species (ROS) generation stimulated by H2O2 in liver AML12 cells. In vivo, MCGP alleviated APAP/CCl4-induced hepatic necrosis and resumed abnormal aminotransferase activities and liver antioxidase activities. In addition, MCGP depressed APAP- or CCl4-induced oxidative stress through the suppression of CYP2E1 and activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MCGP also enhanced the number of PCNA-positive hepatocytes, increased hepatic PCNA and Bcl-XL, and decreased BAX expression in APAP-/CCl4-intoxicated mice. Furthermore, MCGP activated the GSDMD-N/cleaved caspase 1 pathway. In summary, MCGP might act as a potential therapeutic drug against drug-induced and chemical-induced acute liver injuries, and its underlying mechanisms might engage on the pressing of oxidative stress, refraining of hepatocyte apoptosis, and facilitating of liver regeneration.

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“…The expression of NRF2 mRNA is dramatically increased in carbon tetrachloride (CCl 4 ) -induced hepatic fibrotic tissues (Yang et al, 2014); conversely, Nrf2(L)-KO mice with NRF2 deficiency show more severe CCl 4 -induced hepatic lipid, protein, and DNA damage (Lyu et al, 2020). In addition, by stimulating the TGF-1/Smad3 pathway to activate hepatic stellate cells, stimulate ECM synthesis, and create αsmooth muscle actin (a hallmark of myofibroblast activation), Nrf2 knockdown has been shown to trigger a cascade of fibrogenic events (Ghanim and Qinna, 2022).…”

Section: Nrf2 and Hepatic Fibrosismentioning

confidence: 99%

Roles of NRF2 in Fibrotic Diseases: From Mechanisms to Therapeutic Approaches

Hao

Cai

et al. 2022

Front. Physiol.

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Fibrosis is a persistent inflammatory response that causes scarring and tissue sclerosis by stimulating myofibroblasts to create significant quantities of extracellular matrix protein deposits in the tissue. Oxidative stress has also been linked to the development of fibrosis in several studies. The nuclear erythroid 2-related factor 2 (NRF2) transcription factor controls the expression of several detoxification and antioxidant genes. By binding to antioxidant response elements, NRF2 is activated by oxidative or electrophilic stress and promotes its target genes, resulting in a protective effect on cells. NRF2 is essential for cell survival under oxidative stress conditions. This review describes Kelch-like epichlorohydrin-associated protein 1 (KEAP1)/NRF2 signaling mechanisms and presents recent research advances regarding NRF2 and its involvement in primary fibrotic lesions such as pulmonary fibrosis, hepatic fibrosis, myocardial fibrosis, and renal fibrosis. The related antioxidant substances and drugs are described, along with the mechanisms by which KEAP1/NRF2 regulation positively affects the therapeutic response. Finally, the therapeutic prospects and potential value of NRF2 in fibrosis are summarized. Further studies on NRF2 may provide novel therapeutic approaches for fibrosis.

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Nrf2/ARE axis signalling in hepatocyte cellular death

Cited by 14 publications

References 90 publications

Impact of Sustained Exogenous Irisin Myokine Administration on Muscle and Myocyte Integrity in Sprague Dawley Rats

Impact of Sustained Exogenous Irisin Myokine Administration on Muscle and Myocyte Integrity in Sprague Dawley Rats

Methyl 6-O-cinnamoyl-α-d-glucopyranoside Ameliorates Acute Liver Injury by Inhibiting Oxidative Stress Through the Activation of Nrf2 Signaling Pathway

Roles of NRF2 in Fibrotic Diseases: From Mechanisms to Therapeutic Approaches

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