N-acetylcysteine (NAC) alleviates the peripheral neuropathy associated with liver cirrhosis via modulation of neural MEG3/PAR2/ NF-ҡB axis

Mohamed, Doaa I.; Khairy, Eman; Khedr, Sara A.; Habib, Eman K.; Elayat, Wael M.; El-Kharashi, Omnyah A.

doi:10.1016/j.neuint.2019.104602

Cited by 9 publications

(7 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 48 Meanwhile, PAR2 is shown to be closely associated with some downstream pathways in various human diseases, such as PAR2-PI3K/Akt/mTOR in kidney tubular epithelial inflammation, 51 PAR2-MEK-ERK1/2-FOS/MYC/STAT3-COX2 signaling in ovarian cancer, 52 and PAR2-ERK/c-jun/AP-1 pathway in colon cancer. 53 Notably, some of these pathways are confirmed to combine with PAR2 in liver-related diseases, such as PAR2-NF-κB in liver cirrhosis 54 and PAR2-ERK/AP-1 in hepatoma. 55 We speculated that PAR2 may also interact with HBx via these signaling pathways in liver tissues.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Protease Activated Receptor 2 Attenuates HBx-Induced Inflammation and Mitochondria Oxidative Stress

B¹,

Y²,

S³

et al. 2022

IDR

View full text Add to dashboard Cite

Background Hepatitis B virus (HBV) infection is one of the global public problems. Among the known infection cases, HBV X protein (HBx) is one of the key inducements of viral replication and host infection. This study was aimed to uncover the role of protease activated receptor 2 (PAR2) on HBx-induced liver injury. Methods A PAR2-KO mouse model expressing HBx was constructed using hydrodynamics-based in vivo gene transfection method. In addition, pcDNA3.1-HBx was used to over-express HBx in LO 2 cells. The effects of HBx overexpression on inflammation and mitochondria oxidative stress were evaluated. Results We found that PAR2 protein level was increased by HBx overexpression. The enforced HBx inhibited LO 2 cells apoptosis. Meanwhile, HBx induced inflammation reactions through promoting the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and CXCL-2. Overexpressed HBx also resulted in mitochondria oxidative stress by upregulation of ROS level and downregulation of MMP and ATP. However, in FSLLRY-NH 2 (PAR2 antagonist) treated LO 2 cells or PAR2-KO mice, PAR2 blockade reversed the above adverse effects of HBx on liver cells or tissues. Conclusion Inhibition of PAR2 may suppress inflammation and mitochondria oxidative stress caused by HBx, pointing out the potential application values of PAR2 antagonist on the treatment of HBV infection in clinic.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of Protease Activated Receptor 2 Attenuates HBx-Induced Inflammation and Mitochondria Oxidative Stress

B¹,

Y²,

S³

et al. 2022

IDR

View full text Add to dashboard Cite

show abstract

“…As an antioxidant, NAC has been documented to exert antifibrotic effects based on some preliminary human studies (Czaja, 2014). Mohamed et al disclosed that NAC alleviates the liver cirrhosis-associated peripheral neuropathy via suppression of maternally expressed 3 (MEG3)/protease activated receptor 2 (PAR2) expression (Mohamed et al, 2020).…”

Section: Ba Inhibited the Secretion Of Inflammatory Factorsmentioning

confidence: 99%

“…According to the report of Badr et al., propolis possesses the antioxidant properties and can hinder oxidative stress during liver fibrosis (Badr et al., 2019; Selamoglu et al., 2015). Currently, N‐acetylcysteine (NAC), as a known ROS scavenger, alleviates liver cirrhosis‐associated peripheral neuropathy (Mohamed et al., 2020). However, these methods still fail to solve the problem of increasing mortality due to liver cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of baicalin on diethyl nitrosamine‐induced liver cirrhosis by suppressing oxidative stress and inflammation

Wang,

Chang,

Liu

et al. 2023

Chem Biol Drug Des

View full text Add to dashboard Cite

Baicalin (BA) is a natural product extract with anti‐inflammatory, antioxidant, and hepatoprotective properties. Given that the exact underlying mechanisms responsible for the impact of BA on liver cirrhosis remain ambiguous, a detailed investigation is sorely needed. Accordingly, a rat liver cirrhosis model was established via the intraperitoneal injection of diethyl nitrosamine (DEN, 100 mg/kg). Following the modeling, these rats were given BA (100 mg/kg) or N‐acetylcysteine (NAC, 150 mg/kg) alone or in combination. The pathological morphology of rat liver tissues in each group was observed by hematoxylin and eosin staining and Masson's trichrome staining. The expression of fibrosis‐related proteins was evaluated by Western blot, and the levels of liver function‐related biochemical indexes, oxidative stress‐related indexes, and inflammatory factors in the serum by enzyme‐linked immunosorbent assays (ELISA). The level of mitochondrial reactive oxygen species was measured by flow cytometry. The results depicted that in the rat model of DEN‐induced liver cirrhosis, BA reduced the expression of fibrosis‐related proteins (collagen type I alpha 1, α‐smooth muscle actin, and transforming growth factor‐β1), thereby alleviating the structural fibrosis of liver tissue. Furthermore, BA could diminish the level of mitochondrial reactive oxygen species, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), interleukin (IL)‐1β, IL‐6, tumor necrosis factor‐α (TNF‐α), and monocyte chemotactic protein‐1 (MCP‐1), while promoting albumin, superoxide dismutase (SOD), and glutathione peroxidase (GSH‐Px) levels. Notably, all these effects of BA above were strengthened following the combined treatment of BA and NAC. On the whole, BA suppresses liver fibrosis by inhibiting oxidative stress and inflammation, thereby exerting a hepatoprotective effect.

show abstract

“…MEG3 regulates hypoxia-mediated neuron apoptosis through affecting lipoxygenase signaling [ 22 ], a pathway which is found to be disturbed in the brain tissues of BD patients [ 23 ]. RMST and MEG3 lncRNAs contribute in controlling oxidative stress [ 24 ]. LncRNA MT1DP protects cells against oxidative stress, particularly the toxicity of cadmium to hepatocytes [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Significant reduction of long non-coding RNAs expression in bipolar disorder

et al. 2022

View full text Add to dashboard Cite

Long non-coding RNAs (lncRNAs) have been recently emerged as critical modulators of oxidative stress pathway. Likewise, rising evidence currently highlights dysfunction of oxidative stress pathways in bipolar disorder (BD) patients.In the current study, we evaluated the expression levels of H19, SCAL1 (LUCAT1), RMST, MEG3 and MT1DP lncRNAs in the PBMC from 50 patients with BD and 50 control subjects (male/female ratio in each group: 70%/30%). Expression levels of SCAL1, RMST and MEG3 but not H19 and MT1DP were considerably decreased in BD patients compared with healthy individuals. Such significant decrease in the expression of MEG3, RMST and SCAL1 was only reported in male BD patients compared with male controls. Substantial pairwise correlations were observed between expression levels of these lncRNAs in BD subjects. The area under curve values for RMST, MEG3 and SCAL1 were 0.70, 0.63 and 0.61 respectively. On the basis of this finding, RMST had the best efficiency in the discrimination of disease status between BD patients and controls. Taken together, the current results suggest a role for MEG3, RMST and SCAL1 lncRNAs in the pathogenesis of BD. In addition, peripheral expression levels of these lncRNAs might serve as potential peripheral markers for BD.

show abstract

N-acetylcysteine (NAC) alleviates the peripheral neuropathy associated with liver cirrhosis via modulation of neural MEG3/PAR2/ NF-ҡB axis

Cited by 9 publications

References 37 publications

Inhibition of Protease Activated Receptor 2 Attenuates HBx-Induced Inflammation and Mitochondria Oxidative Stress

Inhibition of Protease Activated Receptor 2 Attenuates HBx-Induced Inflammation and Mitochondria Oxidative Stress

Protective effects of baicalin on diethyl nitrosamine‐induced liver cirrhosis by suppressing oxidative stress and inflammation

Significant reduction of long non-coding RNAs expression in bipolar disorder

Contact Info

Product

Resources

About