scholarly journals Value of monitoring Nrf2 activity for the detection of chemical and oxidative stress

2015 ◽  
Vol 43 (4) ◽  
pp. 657-662 ◽  
Author(s):  
Fiona E. Mutter ◽  
B. Kevin Park ◽  
Ian M. Copple
Keyword(s):  
Oxidative Stress ◽  
Mammalian Cells ◽  
Direct Interaction ◽  
Experimental Models ◽  
Related Factor ◽  
Nrf2 Pathway ◽  
Oxidative Stresses ◽  
Therapeutic Drugs ◽  
Numerous Cell ◽  
And Oxidative Stress

Beyond specific limits of exposure, chemical entities can provoke deleterious effects in mammalian cells via direct interaction with critical macromolecules or by stimulating the accumulation of reactive oxygen species (ROS). In particular, these chemical and oxidative stresses can underpin adverse reactions to therapeutic drugs, which pose an unnecessary burden in the clinic and pharmaceutical industry. Novel pre-clinical testing strategies are required to identify, at an earlier stage in the development pathway, chemicals and drugs that are likely to provoke toxicity in humans. Mammalian cells can adapt to chemical and oxidative stress via the action of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which up-regulates the expression of numerous cell defence genes and has been shown to protect against a variety of chemical toxicities. Here, we provide a brief overview of the Nrf2 pathway and summarize novel experimental models that can be used to monitor changes in Nrf2 pathway activity and thus understand the functional consequences of such perturbations in the context of chemical and drug toxicity. We also provide an outlook on the potential value of monitoring Nrf2 activity for improving the pre-clinical identification of chemicals and drugs with toxic liability in humans.

Alpha-1-Antichymotrypsin: a Common Player for Type 2 Diabetes and Alzheimer's Disease

2020 ◽  
Vol 16 ◽  
Author(s):  
Nataly Guzmán-Herrera ◽  
Viridiana C. Pérez-Nájera ◽  
Luis A. Salazar-Olivo
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Regulatory Networks ◽  
Therapeutic Strategies ◽  
Oxidative Stresses ◽  
Bibliographic Search ◽  
And Oxidative Stress

Background: Numerous studies have shown a significant association between type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD), two pathologies affecting millions of people worldwide. Chronic inflammation and oxidative stress are two conditions common to these diseases also affecting the activity of the serpin alpha-1-antichymotrypsin (ACT), but a possible common role for this serpin in T2D and AD remains unclear. Objective: To explore the possible regulatory networks linking ACT to T2D and AD. Materials and Methods: A bibliographic search was carried out in PubMed, Med-line, Open-i, ScienceDirect, Scopus and SpringerLink for data indicating or suggesting association among T2D, AD, and ACT. Searched terms like “alpha-1-antichymotrypsin”, “type 2 diabetes”, “Alzheimer's disease”, “oxidative stress”, “pro-inflammatory mediators” among others were used. Moreover, common therapeutic strategies between T2D and AD as well as the use of ACT as a therapeutic target for both diseases were included. Results: ACT has been linked with development and maintenance of T2D and AD and studies suggest their participation through activation of inflammatory pathways and oxidative stress, mechanisms also associated with both diseases. Likewise, evidences indicate that diverse therapeutic approaches are common to both diseases. Conclusion: Inflammatory and oxidative stresses constitute a crossroad for T2D and AD where ACT could play an important role. In-depth research on ACT involvement in these two dysfunctions could generate new therapeutic strategies for T2D and AD.

Neuroprotection of chromobox 7 knockout in the mouse after cerebral ischemia-reperfusion injury via nuclear factor E2-related factor 2/hemeoxygenase-1 signaling pathway

2021 ◽  
pp. 096032712110361
Author(s):  
Hai-Tao Zhang ◽  
Xi-Zeng Wang ◽  
Qing-Mei Zhang ◽  
Han Zhao
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Water Content ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cerebral Ischemia Reperfusion ◽  
And Oxidative Stress

Objective To explore the mechanism of chromobox 7 (CBX7)-mediated nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway in the cerebral ischemia/reperfusion (I/R) injury. Methods The experimental wild-type (WT) and CBX7-/- mice were used to establish cerebral I/R models using the middle cerebral artery occlusion (MCAO) surgery to determine CBX7 levels at different time points after MCAO injury. For all mice, neurological behavior, infarct size, water content, and oxidative stress–related indicators were determined, and transferase (TdT)-mediated dUTP-biotin nick-end labeling (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)) staining method was employed to observe cell apoptosis, while Western blot to measure the expression of CBX7 and Nrf/HO-1 pathway-related proteins. Results At 6 h, 12 h, 24 h, 3 days, and 7 days after mice with MCAO, CBX7 expression was gradually up-regulated and the peak level was reached at 24 h. Mice in the WT + MCAO group had increased infarct size, with significant increases in the modified neurological severity scores and water content in the brain, as well as the quantity of TUNEL-positive cells. For the oxidative stress-indicators, an increase was seen in the content of MDA (malondial dehyde), but the activity of SOD (superoxide dismutase) and content of GSH-PX (glutathione peroxidase) and CAT (catalase) were decreased; meanwhile, the protein expression of CBX7, HO-1, and nuclear Nrf2 was up-regulated, while the cytoplasmic Nrf2 was down-regulated. Moreover, CBX7 knockout attenuated I/R injury in mice. Conclusion Knockout of CBX7 may protect mice from cerebral I/R injury by reducing cell apoptosis and oxidative stress, possibly via activating the Nrf2/HO-1 pathway.

scholarly journals Antioxidant Therapy in Pancreatitis

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 657
Author(s):  
Lourdes Swentek ◽  
Dean Chung ◽  
Hirohito Ichii
Keyword(s):  
Oxidative Stress ◽  
Chronic Pancreatitis ◽  
Total Pancreatectomy ◽  
Current Status ◽  
Related Factor ◽  
Endocrine Dysfunction ◽  
Deep Dive ◽  
Pathway Activation ◽  
Advanced Therapies ◽  
And Oxidative Stress

Pancreatitis is pathologic inflammation of the pancreas characterized by acinar cell destruction and oxidative stress. Repeated pancreatic insults can result in the development of chronic pancreatitis, characterized by irreversible fibrosis of the pancreas and many secondary sequelae, ultimately leading to the loss of this important organ. We review acute pancreatitis, chronic pancreatitis, and pancreatitis-related complications. We take a close look at the pathophysiology with a focus on oxidative stress and how it contributes to the complications of the disease. We also take a deep dive into the evolution and current status of advanced therapies for management including dietary modification, antioxidant supplementation, and nuclear factor erythroid-2-related factor 2-Kelch-like ECH-associated protein 1(Nrf2-keap1) pathway activation. In addition, we discuss the surgeries aimed at managing pain and preventing further endocrine dysfunction, such as total pancreatectomy with islet auto-transplantation.

Daphnetin Ameliorates Corticosterone-Induced Depressive-Like Behavior and Oxidative Stress in Mice Via Nuclear Factor Erythroid 2-Related Factor/Heme Oxygenase-1 Pathway

2021 ◽  
Vol 19 (4) ◽  
pp. 470-476
Author(s):  
Chao Liu ◽  
Chao Liang ◽  
Jie Huang
Keyword(s):  
Oxidative Stress ◽  
Consumption Rate ◽  
Tail Suspension Test ◽  
Protein Carbonyl ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Sucrose Consumption ◽  
Markers Of Oxidative Stress ◽  
Swimming Test ◽  
And Oxidative Stress

We have investigated the effect of daphnetin on depressive-like behavior and oxidative stress caused by corticosterone in mice. To this end, we have analyzed the effect of corticosterone alone and combination of corticosterone and daphnetin on three behavioral indices of depressive-like behavior - sucrose consumption rate, forced swimming test, and tail suspension test as well as biochemical markers of oxidative stress - malondialdehyde, nitrite, protein carbonyl, nonprotein sulfhydryl and glutathione contents as well as hippocampal cell apoptosis. The results support the conclusion that daphnetin diminished corticosterone induced depressive like behavior and oxidative stress by activating Nrf2/HO-1 pathway.

The Effect of Curcumin Nano-Suspension on Myocardial Fibrosis in Diabetic Rats

2020 ◽  
Vol 12 (10) ◽  
pp. 1215-1220
Author(s):  
Bingshuang Xue ◽  
Yi Xue ◽  
Jiaojiao Zhou ◽  
Qichao Yang
Keyword(s):  
Oxidative Stress ◽  
Myocardial Fibrosis ◽  
Hot Spot ◽  
Health And Safety ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Therapeutic Drugs ◽  
Tnf Α ◽  
Mda Content ◽  
And Oxidative Stress

The occurrence of complications of diabetic patients not only increases the difficulty and burden of treatment but also significantly affects the health and safety of patients. Traditional therapeutic drugs are prone to drug resistance, which affects the therapeutic effect. In recent years, the application of plant-derived natural compounds in the treatment of diseases has become a hot spot in the research of diabetes drugs. Curcumin has anti-tumor, anti-inflammation, anti-oxidation and antimicrobial effects, but the mechanism of its effect on cardiomyocytes in diabetic patients is not yet clear. In this study, curcumin was prepared into nano-preparations and its mechanism of action in the process of myocardial fibrosis in diabetic rats was further explored. We found that injection of curcumin nano-suspension can increase the LVIDd and LVFS of rats, while reducing the serum CKMB, LDH, AST and cTnI levels. Further exploration found that curcumin can reduce serum TNF- α and IL-1 β levels in diabetic rats, while increasing the SOD and GSH-Px activities of myocardial tissue, and reducing MDA content. These suggests that curcumin can reduce inflammation and oxidative stress in diabetic rats. Therefore, this study believes that curcumin nano-suspension can effectively inhibit diabetic cardiomyocyte fibrosis, oxidative stress, and inflammation and protect the rat myocardium.

A Synergistic Antimicrobial Mechanism of GO: Why Oxidative Stress Can Inactivate E. coli

NANO ◽  
2020 ◽  
Vol 15 (04) ◽  
pp. 2050054 ◽  
Author(s):  
Xin Li ◽  
Haoqi Zhao ◽  
Shidong Wang ◽  
Weiwu Zou ◽  
Peiyan Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antibacterial Activity ◽  
Mammalian Cells ◽  
Water Solubility ◽  
Direct Interaction ◽  
Medical Application ◽  
Future Application ◽  
Sem Images ◽  
E Coli ◽  
Low Cytotoxicity

Graphene oxide (GO), a 2D nanomaterial, is a promising material for medical application, thanks to its water solubility, antibacterial activity and relatively low cytotoxicity. However, many factors, such as lateral dimension, purity and surface chemistry, may influence its antibacterial activity, its exact mechanism is still unknown. In this work, E. coli was used as model bacterium to determine the antibacterial activity of well-dispersed GO which was obtained by a modified Hummer method and dialyzed to remove the salts and acid used in the oxidation process. After co-culture with GO for 2[Formula: see text]h, up to 90% E. coli cells were inactivated when GO concentration at 8[Formula: see text][Formula: see text]g/mL. The direct interaction was not detected in FE-SEM images and the results of [Formula: see text] potential showed that the interaction between GO and E. coli are repulsive[Formula: see text] Our results showed that GO can produce ROS and inactivate SOD and CAT enzymes in low concentration after co-cultured with E. coli which explained the antibacterial activity of GO in aqueous solution. Meanwhile, GO, with high purity, showed low cytotoxicity towards mammalian cells and did not cause any observable hemoglobin after co-cultured with blood cells. The data presented here prove that GO is effectively inhibit E. coli through inactivating SOD, CAT enzymes and the oxidative stress produced by ROS. Furthermore, the good biocompatibility promised its future application.

scholarly journals Maggot Extracts Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis via the Activation of Nrf2

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Rong Wang ◽  
Yongzheng Luo ◽  
Yadong Lu ◽  
Daojuan Wang ◽  
Tingyu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Experimental Colitis ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Related Factor ◽  
Protective Effects ◽  
Protein Levels ◽  
Bowel Diseases ◽  
Effective Therapeutic Strategy ◽  
And Oxidative Stress

Ulcerative colitis (UC) is a common chronic remitting disease driven through altered immune responses with production of inflammatory cytokines. Oxidant/antioxidant balance is also suggested to be an important factor for the recurrence and progression of UC. Maggots are known as a traditional Chinese medicine also known as “wu gu chong.” NF-E2-related factor-2 (Nrf2) transcription factor regulates the oxidative stress response and also represses inflammation. The aim of this study was to investigate the effects of maggot extracts on the amelioration of inflammation and oxidative stress in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and evaluate if the maggot extracts could repress inflammation and oxidative stress using RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In the present study, we found that the maggot extracts significantly prevented the loss of body weight and shortening of colon length in UC induced by DSS. Furthermore, DSS-induced expression of proinflammatory cytokines at both mRNA and protein levels in the colon was also attenuated by the maggot extracts. In addition, the maggot extracts could significantly suppress the expression of interleukin- (IL-) 1β, IL-6, TNF-α, NFκB p65, p-IκB, p22-phox, and gp91-phox in LPS-stimulated RAW 264.7 cells and colonic tissues. The maggot extracts increased the level of Nrf2 and prevented the degradation of Nrf2 through downregulating the expression of Keap1, which resulted in augmented levels of HO-1, SOD, and GSH-Px and reduced levels of MPO and MDA. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of the maggot extracts in mice with colitis and RAW 264.7 cells. Taken together, our data for the first time confirmed that the maggot extracts ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf2/HO-1 pathway. This study sheds light on the possible development of an effective therapeutic strategy for inflammatory bowel diseases.

scholarly journals Curcumin Attenuates Oxaliplatin-Induced Liver Injury and Oxidative Stress by Activating the Nrf2 Pathway

2020 ◽  
Vol Volume 14 ◽  
pp. 73-85 ◽  
Author(s):  
Yulei Lu ◽  
Shengming Wu ◽  
Bangde Xiang ◽  
Lequn Li ◽  
Youzhi Lin
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Nrf2 Pathway ◽  
And Oxidative Stress

scholarly journals Basic Concepts on the Role of Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) in Age-Related Diseases

2019 ◽  
Vol 20 (13) ◽  
pp. 3208 ◽  
Author(s):  
Fabiane Valentini Francisqueti-Ferron ◽  
Artur Junio Togneri Ferron ◽  
Jéssica Leite Garcia ◽  
Carol Cristina Vágula de Almeida Silva ◽  
Mariane Róvero Costa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcriptional Factor ◽  
Future Research ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Pathway ◽  
Age Related ◽  
Basic Concepts

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is one of the most important oxidative stress regulator in the human body. Once Nrf2 regulates the expression of a large number of cytoprotective genes, it plays a crucial role in the prevention of several diseases, including age-related disorders. However, the involvement of Nrf2 on these conditions is complex and needs to be clarified. Here, a brief compilation of the Nrf2 enrollment in the pathophysiology of the most common age-related diseases and bring insights for future research on the Nrf2 pathway is described. This review shows a controversial response of this transcriptional factor on the presented diseases. This reinforces the necessity of more studies to investigate modulation strategies for Nrf2, making it a possible therapeutic target in the treatment of age-related disorders.

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