scholarly journals Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1859
Author(s):  
Muthu Thiruvengadam ◽  
Baskar Venkidasamy ◽  
Umadevi Subramanian ◽  
Ramkumar Samynathan ◽  
Mohammad Ali Ali Shariati ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pathological Condition ◽  
Epigallocatechin Gallate ◽  
The Body ◽  
Related Factor ◽  
In Vivo Models ◽  
Dietary Phytochemicals ◽  
Antioxidant Defense Systems

Oxidative stress is a pathological condition occurring due to an imbalance between the oxidants and antioxidant defense systems in the body. Nuclear factor E2-related factor 2 (NRF2), encoded by the gene NFE2L2, is the master regulator of phase II antioxidant enzymes that protect against oxidative stress and inflammation. NRF2/ARE signaling has been considered as a promising target against oxidative stress-mediated diseases like diabetes, fibrosis, neurotoxicity, and cancer. The consumption of dietary phytochemicals acts as an effective modulator of NRF2/ARE in various acute and chronic diseases. In the present review, we discussed the role of NRF2 in diabetes, Alzheimer’s disease (AD), Parkinson’s disease (PD), cancer, and atherosclerosis. Additionally, we discussed the phytochemicals like curcumin, quercetin, resveratrol, epigallocatechin gallate, apigenin, sulforaphane, and ursolic acid that have effectively modified NRF2 signaling and prevented various diseases in both in vitro and in vivo models. Based on the literature, it is clear that dietary phytochemicals can prevent diseases by (1) blocking oxidative stress-inhibiting inflammatory mediators through inhibiting Keap1 or activating Nrf2 expression and its downstream targets in the nucleus, including HO-1, SOD, and CAT; (2) regulating NRF2 signaling by various kinases like GSK3beta, PI3/AKT, and MAPK; and (3) modifying epigenetic modulation, such as methylation, at the NRF2 promoter region; however, further investigation into other upstream signaling molecules like NRF2 and the effect of phytochemicals on them still need to be investigated in the near future.

scholarly journals Vascular Dysfunction Induced by Mercury Exposure

2019 ◽  
Vol 20 (10) ◽  
pp. 2435 ◽  
Author(s):  
Tetsuya Takahashi ◽  
Takayoshi Shimohata
Keyword(s):  
Oxidative Stress ◽  
Vascular Dysfunction ◽  
Brain Parenchyma ◽  
Transport Systems ◽  
Mehg Exposure ◽  
In Vivo Models ◽  
The Central Nervous System ◽  
The Brain

Methylmercury (MeHg) causes severe damage to the central nervous system, and there is increasing evidence of the association between MeHg exposure and vascular dysfunction, hemorrhage, and edema in the brain, but not in other organs of patients with acute MeHg intoxication. These observations suggest that MeHg possibly causes blood–brain barrier (BBB) damage. MeHg penetrates the BBB into the brain parenchyma via active transport systems, mainly the l-type amino acid transporter 1, on endothelial cell membranes. Recently, exposure to mercury has significantly increased. Numerous reports suggest that long-term low-level MeHg exposure can impair endothelial function and increase the risks of cardiovascular disease. The most widely reported mechanism of MeHg toxicity is oxidative stress and related pathways, such as neuroinflammation. BBB dysfunction has been suggested by both in vitro and in vivo models of MeHg intoxication. Therapy targeted at both maintaining the BBB and suppressing oxidative stress may represent a promising therapeutic strategy for MeHg intoxication. This paper reviews studies on the relationship between MeHg exposure and vascular dysfunction, with a special emphasis on the BBB.

scholarly journals Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists

2021 ◽  
Vol 22 (19) ◽  
pp. 10822
Author(s):  
Agata Winiarska ◽  
Monika Knysak ◽  
Katarzyna Nabrdalik ◽  
Janusz Gumprecht ◽  
Tomasz Stompór
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Kidney Injury ◽  
Organ Protection ◽  
In Vivo Models ◽  
Diabetic Kidney ◽  
And Oxidative Stress

The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) antagonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R antagonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases.

scholarly journals In Vitro and In Vivo Inhibitory Effect of Citrus Junos Tanaka Peel Extract against Oxidative Stress-Induced Apoptotic Death of Lung Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1231
Author(s):  
Jin Woo Kim ◽  
Eun Hee Jo ◽  
Ji Eun Moon ◽  
Hanvit Cha ◽  
Moon Han Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Inhibitory Effect ◽  
Lung Cells ◽  
In Vivo Models ◽  
Citrus Junos ◽  
Induced Apoptosis ◽  
Peel Extract

Various stresses derived from both internal and external oxidative environments lead to the excessive production of reactive oxygen species (ROS) causing progressive intracellular oxidative damage and ultimately cell death. The objective of this study was to evaluate the protective effects of Citrus junos Tanaka peel extract (CE) against oxidative-stress induced the apoptosis of lung cells and the associated mechanisms of action using in vitro and in vivo models. The protective effect of CE was evaluated in vitro in NCI-H460 human lung cells exposed to pro-oxidant H2O2. The preventive effect of CE (200 mg/kg/day, 10 days) against pulmonary injuries following acrolein inhalation (10 ppm for 12 h) was investigated using an in vivo mouse model. Herein, we demonstrated the inhibitory effect of CE against the oxidative stress-induced apoptosis of lung cells under a highly oxidative environment. The function of CE is linked with its ability to suppress ROS-dependent, p53-mediated apoptotic signaling. Furthermore, we evaluated the protective role of CE against apoptotic pulmonary injuries associated with the inhalation of acrolein, a ubiquitous and highly oxidizing environmental respiratory pollutant, through the attenuation of oxidative stress. The results indicated that CE exhibits a protective effect against the oxidative stress-induced apoptosis of lung cells in both in vitro and in vivo models.

scholarly journals Combination of Epigallocatechin Gallate and Sulforaphane Counteracts In Vitro Oxidative Stress and Delays Stemness Loss of Amniotic Fluid Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Pasquale Marrazzo ◽  
Cristina Angeloni ◽  
Michela Freschi ◽  
Antonello Lorenzini ◽  
Cecilia Prata ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Stem Cell ◽  
Amniotic Fluid ◽  
Osteogenic Differentiation ◽  
Epigallocatechin Gallate ◽  
The Body ◽  
Gene Markers ◽  
Amniotic Fluid Stem Cells

Amniotic fluid stem cells (AFSCs) are characterized in vivo by a unique niche guarantying their homeostatic role in the body. Maintaining the functionality of stem cells ex vivo for clinical applications requires a continuous improvement of cell culture conditions. Cellular redox status plays an important role in stem cell biology as long as reactive oxygen species (ROS) concentration is finely regulated and their adverse effects are excluded. The aim of this study was to investigate the protective effect of two antioxidants, sulforaphane (SF) and epigallocatechin gallate (EGCG), against in vitro oxidative stress due to hyperoxia and freeze-thawing cycles in AFSCs. Human AFSCs were isolated and characterized from healthy subjects. Assays of metabolic function and antioxidant activity were performed to investigate the effect of SF and EGCG cotreatment on AFSCs. Real-time PCR was used to investigate the effect of the cotreatment on pluripotency, senescence, osteogenic and adipogenic markers, and antioxidant enzymes. Alkaline phosphatase assays and Alizarin Red staining were used to confirm osteogenic differentiation. The cotreatment with SF and EGCG was effective in reducing ROS production, increasing GSH levels, and enhancing the endogenous antioxidant defences through the upregulation of glutathione reductase, NAD(P)H:quinone oxidoreductase-1, and thioredoxin reductase. Intriguingly, the cotreatment sustained the stemness state by upregulating pluripotency markers such as OCT4 and NANOG. Moreover, the cotreatment influenced senescence-associated gene markers in respect to untreated cells. The cotreatment upregulated osteogenic gene markers and promoted osteogenic differentiation in vitro. SF and EGCG can be used in combination in AFSC culture as a strategy to preserve stem cell functionality.

scholarly journals Anti-adipogenic and anti-obesity activities of purpurin in 3T3-L1 preadipocyte cells and in mice fed a high-fat diet

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Woo Nam ◽  
Seok Hyun Nam ◽  
Sung Phil Kim ◽  
Carol Levin ◽  
Mendel Friedman
Keyword(s):  
Weight Gain ◽  
High Fat Diet ◽  
Biological Activities ◽  
The Body ◽  
High Fat ◽  
In Vivo Models ◽  
Triglyceride Accumulation ◽  
In Cells

Abstract Background The body responds to overnutrition by converting stem cells to adipocytes. In vitro and in vivo studies have shown polyphenols and other natural compounds to be anti-adipogenic, presumably due in part to their antioxidant properties. Purpurin is a highly antioxidative anthraquinone and previous studies on anthraquinones have reported numerous biological activities in cells and animals. Anthraquinones have also been used to stimulate osteoblast differentiation, an inversely-related process to that of adipocyte differentiation. We propose that due to its high antioxidative properties, purpurin administration might attenuate adipogenesis in cells and in mice. Methods Our study will test the effect purpurin has on adipogenesis using both in vitro and in vivo models. The in vitro model consists of tracking with various biomarkers, the differentiation of pre-adipocyte to adipocytes in cell culture. The compound will then be tested in mice fed a high-fat diet. Murine 3T3-L1 preadipocyte cells were stimulated to differentiate in the presence or absence of purpurin. The following cellular parameters were measured: intracellular reactive oxygen species (ROS), membrane potential of the mitochondria, ATP production, activation of AMPK (adenosine 5′-monophosphate-activated protein kinase), insulin-induced lipid accumulation, triglyceride accumulation, and expression of PPARγ (peroxisome proliferator activated receptor-γ) and C/EBPα (CCAAT enhancer binding protein α). In vivo, mice were fed high fat diets supplemented with various levels of purpurin. Data collected from the animals included anthropometric data, glucose tolerance test results, and postmortem plasma glucose, lipid levels, and organ examinations. Results The administration of purpurin at 50 and 100 μM in 3T3-L1 cells, and at 40 and 80 mg/kg in mice proved to be a sensitive range: the lower concentrations affected several measured parameters, whereas at the higher doses purpurin consistently mitigated biomarkers associated with adipogenesis, and weight gain in mice. Purpurin appears to be an effective antiadipogenic compound. Conclusion The anthraquinone purpurin has potent in vitro anti-adipogenic effects in cells and in vivo anti-obesity effects in mice consuming a high-fat diet. Differentiation of 3T3-L1 cells was dose-dependently inhibited by purpurin, apparently by AMPK activation. Mice on a high-fat diet experienced a dose-dependent reduction in induced weight gain of up to 55%.

scholarly journals Ocular Delivery of Polyphenols: Meeting the Unmet Needs

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 370
Author(s):  
Luna Krstić ◽  
María J. González-García ◽  
Yolanda Diebold
Keyword(s):  
Oxidative Stress ◽  
Polyphenolic Compounds ◽  
In Vivo Models ◽  
Structural Peculiarities ◽  
Inflammatory Processes ◽  
Delivery Strategies ◽  
Low Solubility ◽  
Ocular Therapy

Nature has become one of the main sources of exploration for researchers that search for new potential molecules to be used in therapy. Polyphenols are emerging as a class of compounds that have attracted the attention of pharmaceutical and biomedical scientists. Thanks to their structural peculiarities, polyphenolic compounds are characterized as good scavengers of free radical species. This, among other medicinal effects, permits them to interfere with different molecular pathways that are involved in the inflammatory process. Unfortunately, many compounds of this class possess low solubility in aqueous solvents and low stability. Ocular pathologies are spread worldwide. It is estimated that every individual at least once in their lifetime experiences some kind of eye disorder. Oxidative stress or inflammatory processes are the basic etiological mechanisms of many ocular pathologies. A variety of polyphenolic compounds have been proved to be efficient in suppressing some of the indicators of these pathologies in in vitro and in vivo models. Further application of polyphenolic compounds in ocular therapy lacks an adequate formulation approach. Therefore, more emphasis should be put in advanced delivery strategies that will overcome the limits of the delivery site as well as the ones related to the polyphenols in use. This review analyzes different drug delivery strategies that are employed for the formulation of polyphenolic compounds when used to treat ocular pathologies related to oxidative stress and inflammation.

Probiotic yeast Kluyveromyces marxianus CIDCA 8154 shows anti-inflammatory and anti-oxidative stress properties in in vivo models

2016 ◽  
Vol 7 (1) ◽  
pp. 83-93 ◽  
Author(s):  
D.E. Romanin ◽  
S. Llopis ◽  
S. Genovés ◽  
P. Martorell ◽  
V.D. Ramón ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kluyveromyces Marxianus ◽  
Intestinal Inflammation ◽  
In Vivo Models ◽  
Benzene Sulfonic Acid ◽  
Bowel Diseases ◽  
Probiotic Yeast ◽  
Anti Inflammatory

Inflammatory bowel diseases (IBDs) are complex affections with increasing incidence worldwide. Multiple factors are involved in the development and maintenance of the symptoms including enhanced oxidative stress in intestinal mucosa. The conventional therapeutic approaches for IBDs are based on the use anti-inflammatory drugs with important collateral effects and partial efficacy. In the present work we tested the anti-inflammatory capacity of Kluyveromyces marxianus CIDCA 8154 in different models. In vitro, we showed that the pretreatment of epithelial cells with the yeast reduce the levels of intracellular reactive oxygen species. Furthermore, in a murine model of trinitro benzene sulfonic acid-induced colitis, yeast-treated animals showed a reduced histopathological score (P<0.05) and lower levels of circulating interleukin 6 (P<0.05). The capacity to modulate oxidative stress in vivo was assessed using a Caenorhabditis elegans model. The yeast was able to protect the nematodes from oxidative stress by modulating the SKN-1 transcription factor trough the DAF-2 pathway. These results indicate that K. marxianus CIDCA 8154 could control the intestinal inflammation and cellular oxidative stress. Deciphering the mechanisms of action of different probiotics might be useful for the rational formulation of polymicrobial products containing microorganisms targeting different anti-inflammatory pathways.

scholarly journals Experimental Models in Rheumatoid Arthritis:

2020 ◽  
Vol 8 (1) ◽  
pp. 119-134
Author(s):  
Verônica Assalin Zorgetto-Pinheiro ◽  
Alexandre Meira de Vasconcelos ◽  
Rafael Sanaiotte Pinheiro ◽  
Danielle Bogo ◽  
Iandara Schettert Silva
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Testing ◽  
Pathological Condition ◽  
In Vitro Models ◽  
Experimental Models ◽  
In Vivo Models ◽  
Methodological Tool ◽  
Class 1

Rheumatoid arthritis is an autoimmune and chronic pathological condition characterized by an inflammatory process of the joints It is a complex and multifactorial, involving genetic, epigenetic and environmental factors and the use of experimental models is required to better understand its pathology and for drug testing. The aim of this study was to perform a systematic literature review on experimental models in rheumatoid arthritis using IRAMUTEQ, a software that analysis, qualitatively and quantitatively, text fragments, as a methodological tool. After searching for articles published in the last five years on Scopus database and applying the exclusion criteria, we ended with 84 articles. The most commonly employed experimental models was the arthritis induction by inoculation of the Complete Freund's Adjuvant (CFA), followed by the use of combined methodologies and the collagen-induced arthritis (CIA). The analyses of abstracts by the IRAMUTEQ software provided a classification according to their textual elements in four classes, which were grouped into three main themes: in vivo models (class 1), clinical practice and traditional medicine (classes 2 and 3) and in vitro models (class 4) and it was also possible to build a similarity tree of the terms present in the abstracts and a word cloud with the most cited terms. Thus, the use of the IRAMUTEQ software as a methodological tool has been satisfactory, since it was possible to identify the main experimental models used, keywords, pathological processes and molecules involved in the pathogenesis of rheumatoid arthritis free of the researchers’ bias, in addition to being a tool for visual and intuitive results.

scholarly journals Chloroquine and Gemifloxacin Potentiate the Anticancer Effect of Doxorubicin: In-Vitro and In-Vivo Models

2019 ◽  
Vol 12 (04) ◽  
pp. 1613-1620
Author(s):  
Sahar Ezeldien ◽  
Waleed F Khalil ◽  
Mostafa Fayez ◽  
Mohamed M. Abdel-Daim
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Hematological Parameters ◽  
In Vivo Models ◽  
Doxorubicin Treatment ◽  
Blood Biochemical ◽  
Antitumor Properties ◽  
A549 Lung

Doxorubicin is one of the most effective anthracycline anticancer drugs, but it causes several adverse effects. Our study was designed to assess the consequences of combining doxorubicin with chloroquine or gemifloxacin. Drugs cytotoxicity was assessed on two different cell lines; A549 lung adenocarcinoma and MCF7 breast cancer. The in-vitro oxidative stress was also measured. In the in-vivo experiment, Ehrlich ascetis carcinoma-bearing mice, different treatments with doxorubicin, chloroquine, gemifloxacin and their combinations were evaluated. Survival indices (MST and ILS%) and blood biochemical parameters as well as the histopathological picture were studied. Results showed that, doxorubicin combinations were more cytotoxic on MCF7 and A549 cell lines than doxorubicin alone. The combinations significantly decreased the oxidative stress resulted from doxorubicin treatment. Furthermore, these combinations improved hematological parameters and histopathological pictures in the treated mice. In conclusion, chloroquine and gemifloxacin significantly enhance the antitumor properties of doxorubicin and reduce its toxicity.

scholarly journals Natural and Synthetic Polymers for Bone Scaffolds Optimization

Polymers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 905 ◽  
Author(s):  
Francesca Donnaloja ◽  
Emanuela Jacchetti ◽  
Monica Soncini ◽  
Manuela T. Raimondi
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue ◽  
Bone Cells ◽  
The Body ◽  
Bone Tissue Regeneration ◽  
In Vivo Models ◽  
Polymeric Scaffold ◽  
Technology Improvement

Bone tissue is the structural component of the body, which allows locomotion, protects vital internal organs, and provides the maintenance of mineral homeostasis. Several bone-related pathologies generate critical-size bone defects that our organism is not able to heal spontaneously and require a therapeutic action. Conventional therapies span from pharmacological to interventional methodologies, all of them characterized by several drawbacks. To circumvent these effects, tissue engineering and regenerative medicine are innovative and promising approaches that exploit the capability of bone progenitors, especially mesenchymal stem cells, to differentiate into functional bone cells. So far, several materials have been tested in order to guarantee the specific requirements for bone tissue regeneration, ranging from the material biocompatibility to the ideal 3D bone-like architectural structure. In this review, we analyse the state-of-the-art of the most widespread polymeric scaffold materials and their application in in vitro and in vivo models, in order to evaluate their usability in the field of bone tissue engineering. Here, we will present several adopted strategies in scaffold production, from the different combination of materials, to chemical factor inclusion, embedding of cells, and manufacturing technology improvement.

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