Inhibition of the Nrf2 signaling pathway involved in imidacloprid‐induced liver fibrosis in <i>Coturnix japonica</i>

Deng, Ning; Lv, Yueying; Bing, Qizheng; Li, Siyu; Han, Bing; Jiang, Huijie; Yang, Qingyue; Wang, Xiaoqiao; Wu, Pengfei; Liu, Yan; Zhang, Zhigang

doi:10.1002/tox.23601

Cited by 7 publications

(5 citation statements)

References 96 publications

(151 reference statements)

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“…Current studies have shown that liver fibrosis is a chronic progressive pathological state characterized by excessive accumulation of fibrous connective tissue in the liver. [27][28][29][30] It usually leads to liver cirrhosis, portal hypertension, and eventually liver failure. Metabolic liver disease, alcohol abuse, viral infection hepatitis, autoimmune attack, cholestasis and genetic diseases are the main factors leading to the onset of liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

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Exosome‐derived miR‐142‐5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB

Zhao

Jiang

et al. 2023

Environmental Toxicology

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Background This study aims to explore the effect of liver stem cells (LSCs)‐derived exosomes and the miR‐142a‐5p carried by them on the process of fibrosis by regulating macrophages polarization. Methods In this study, CCL4 was used to establish liver fibrosis model. The morphology and purity of exosomes (EVs) were verified by transmission electron microscopy, western blotting (WB) and nanoparticle tracing analysis (NTA). Real‐time quantitative PCR (qRT‐PCR), WB and enzyme‐linked immunoadsorption (ELISA) were used to detect liver fibrosis markers, macrophage polarization markers and liver injury markers. Histopathological assays were used to verify the liver injury morphology in different groups. The cell co‐culture model and liver fibrosis model were constructed to verify the expression of miR‐142a‐5p and ctsb. Results Immunofluorescence of LSCs markers CK‐18, epithelial cell adhesion molecule (EpCam), and AFP showed that these markers were up‐regulated in LSCs. In addition, we evaluated the ability of LSCs to excrete EVs by labeling LSCs‐EVs with PKH67. We found that CCL4 and EVs were simultaneously treated at 50 and 100 μg doses, and both doses of EVs could reduce the degree of liver fibrosis in mice. We tested markers of M1 or M2 macrophage polarization and found that EVs reduced M1 marker expression and promoted M2 marker expression. Further, ELISA was used to detect the secreted factors related to M1 and M2 in tissue lysates, which also verified the above views. Further analysis showed that the expression of miR‐142a‐5p increased significantly with the increase of EVs treatment concentration and time. Further, in vitro and in vivo LSCs‐EVs regulate macrophage polarization through miR‐142a‐5p/ctsb pathway and affect the process of liver fibrosis. Conclusion Our data suggest that EVs‐derived miR‐142‐5p from LSCs improves the progression of liver fibrosis by regulating macrophage polarization through ctsb.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exosome‐derived miR‐142‐5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB

Zhao

Jiang

et al. 2023

Environmental Toxicology

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“…DON caused a drop in GSH-Px activity and other indicators of the glutathione redox system relative to baseline. Researchers found that adding LUT to quail livers alleviated oxidative stress and mitochondrion injury caused by Imidacloprid [ 14 ]. The liver and serum antioxidant levels were significantly reduced when LUT and AC were added to the feed of broilers exposed to DON ( Table 3 ).…”

Section: Discussionmentioning

confidence: 99%

“…The flavonoid LUT is a plant derivative in parsley, chamomile tea, celery, fruits, perilla leaf, and green pepper. It possesses antioxidant, anti-inflammatory, absorbing oxygen, anti-cancer, and DNA repair properties [ 14 , 15 ]. In prior experimental trials, LUT has a broadly positive effect as cardioprotective and neuroprotective [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Ameliorative Effects of Luteolin and Activated Charcoal on Growth Performance, Immunity Function, and Antioxidant Capacity in Broiler Chickens Exposed to Deoxynivalenol

Hassan

Wang

Rajput

et al. 2023

Toxins

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Deoxynivalenol (DON, Vomitoxin) is a threatening mycotoxin that mainly produces oxidative stress and leads to hepatotoxicity in poultry. Antioxidant dietary supplements dramatically boost immunity, safeguarding animals from DON poisoning. Luteolin (LUT) is an active plant-derived compound that poses influential antioxidants. This study explored the effectiveness of LUT in combination with activated charcoal (AC) in detoxifying DON in broilers. The 180 one-day broiler chickens were allocated into five different groups having six replicates in each group, provided with ad libitum feed during the trial period (28 days) as follows: in the control group, basal diet (feed with no supplementation of LUT, AC or DON); in group 2, a basal diet added with 10 mg/kg DON from contaminated culture (DON); in group 3, a basal diet augmented by 350 mg/kg LUT and DON 10 mg/kg (DON + LUT); in group 4, a basal diet supplemented by DON 10 mg/kg + AC 200 mg/kg (DON + AC); and in group 5, a basal diet supplemented by 10 mg/kg DON + 350 mg/kg LUT + 200 mg/kg AC (DON + LUT + AC). Concerning the control group, the DON-treated broilers demonstrated a significant decrease in growth performance (p < 0.05) and serum immunoglobulin (p < 0.05) contents, negatively changing the serum biochemical contents and enzymatic activities and an increase in histopathological liver lesions. Furthermore, DON substantially increased (p < 0.05) malondialdehyde (MDA) concentration and decreased total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels in the serum and liver. The intake of AC and LUT to the DON-contaminated diet decreased DON residue in the liver and potentially reduced the adverse effects of DON. Considering the results, supplementation of LUT with mycotoxin adsorbent has protective effects against mycotoxicosis caused by DON. It could be helpful for the development of novel treatments to combat liver diseases in poultry birds. Our findings may provide important information for applying LUT and AC in poultry production.

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“…It observably changed the fibrosis-related genes in quail livers, leading to hematologic toxicity, hepatic steatosis, inflammation, and downregulation of the Nrf2 pathway. However, as an Nrf2 activator, luteolin markedly reversed these changes ( Deng et al, 2022 ).…”

Section: Protective Effects Of Flavones Targeting Nrf2mentioning

confidence: 99%

Nrf2-mediated therapeutic effects of dietary flavones in different diseases

Huang,

Zhong,

Gao

et al. 2023

Front. Pharmacol.

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Oxidative stress (OS) is a pathological status that occurs when the body’s balance between oxidants and antioxidant defense systems is broken, which can promote the development of many diseases. Nrf2, a redox-sensitive transcription encoded by NFE2L2, is the master regulator of phase II antioxidant enzymes and cytoprotective genes. In this context, Nrf2/ARE signaling can be a compelling target against OS-induced diseases. Recently, natural Nrf2/ARE regulators like dietary flavones have shown therapeutic potential in various acute and chronic diseases such as diabetes, neurodegenerative diseases, ischemia-reperfusion injury, and cancer. In this review, we aim to summarize nrf2-mediated protective effects of flavones in different conditions. Firstly, we retrospected the mechanisms of how flavones regulate the Nrf2/ARE pathway and introduced the mediator role Nrf2 plays in inflammation and apoptosis. Then we review the evidence that flavones modulated Nrf2/ARE pathway to prevent diseases in experimental models. Based on these literature, we found that flavones could regulate Nrf2 expression by mechanisms below: 1) dissociating the binding between Nrf2 and Keap1 via PKC-mediated Nrf2 phosphorylation and P62-mediated Keap1 autophagic degradation; 2) regulating Nrf2 nuclear translocation by various kinases like AMPK, MAPKs, Fyn; 3) decreasing Nrf2 ubiquitination and degradation via activating sirt1 and PI3K/AKT-mediated GSK3 inhibition; and 4) epigenetic alternation of Nrf2 such as demethylation at the promoter region and histone acetylation. In conclusion, flavones targeting Nrf2 can be promising therapeutic agents for various OS-related disorders. However, there is a lack of investigations on human subjects, and new drug delivery systems to improve flavones’ treatment efficiency still need to be developed.

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Inhibition of the Nrf2 signaling pathway involved in imidacloprid‐induced liver fibrosis in Coturnix japonica

Cited by 7 publications

References 96 publications

Exosome‐derived miR‐142‐5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB

Exosome‐derived miR‐142‐5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB

Ameliorative Effects of Luteolin and Activated Charcoal on Growth Performance, Immunity Function, and Antioxidant Capacity in Broiler Chickens Exposed to Deoxynivalenol

Nrf2-mediated therapeutic effects of dietary flavones in different diseases

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