scholarly journals Dietary Supplement Enriched in Antioxidants and Omega-3 Promotes Glutamine Synthesis in Müller Cells: A Key Process against Oxidative Stress in Retina

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3216
Author(s):  
Maryvonne Ardourel ◽  
Chloé Felgerolle ◽  
Arnaud Pâris ◽  
Niyazi Acar ◽  
Khaoula Ramchani Ben Othman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Müller Cells ◽  
Nutritional Supplement ◽  
Glutamine Metabolism ◽  
Muller Cells ◽  
Omega 3 ◽  
Glutamine Synthesis ◽  
The Impact

To prevent ocular pathologies, new generation of dietary supplements have been commercially available. They consist of nutritional supplement mixing components known to provide antioxidative properties, such as unsaturated fatty acid, resveratrol or flavonoids. However, to date, only one preclinical study has evaluated the impact of a mixture mainly composed of those components (Nutrof Total®) on the retina and demonstrated that in vivo supplementation prevents the retina from structural and functional injuries induced by light. Considering the crucial role played by the glial Müller cells in the retina, particularly to regulate the glutamate cycle to prevent damage in oxidative stress conditions, we questioned the impact of this ocular supplement on the glutamate metabolic cycle. To this end, various molecular aspects associated with the glutamate/glutamine metabolism cycle in Müller cells were investigated on primary Müller cells cultures incubated, or not, with the commercially mix supplement before being subjected, or not, to oxidative conditions. Our results demonstrated that in vitro supplementation provides guidance of the glutamate/glutamine cycle in favor of glutamine synthesis. These results suggest that glutamine synthesis is a crucial cellular process of retinal protection against oxidative damages and could be a key step in the previous in vivo beneficial results provided by the dietary supplementation.

scholarly journals Geniposide Attenuates Hyperglycemia-Induced Oxidative Stress and Inflammation by Activating the Nrf2 Signaling Pathway in Experimental Diabetic Retinopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yuanyuan Tu ◽  
Lele Li ◽  
Linling Zhu ◽  
Yang Guo ◽  
Shu Du ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Signaling Pathway ◽  
Cell Activation ◽  
Müller Cells ◽  
In Vivo Model ◽  
Muller Cells ◽  
Nrf2 Signaling Pathway

Geniposide (GEN) is a natural antioxidant and anti-inflammatory product and plays an important role in the treatment of diabetes and diabetic complications. To explore the biological functions and mechanism of GEN in diabetic retinopathy (DR), we constructed the in vitro and in vivo model of DR by using primary cultured mouse retinal Müller cells and C57BL/6 mice, respectively. We found that GEN inhibited ROS accumulation, NF-κB activation, Müller cell activation, and inflammatory cytokine secretion both in vitro and in vivo, which is probably mediated through the Nrf2 pathway. Exendin (9-39) (EX-9), an antagonist of glucagon-like peptide-1 receptor (GLP-1R), abolished the protective effect of GEN on high glucose- (HG-) induced Müller cells. Additionally, GEN decreased hyperglycemia-induced damage to Müller cells and blood-retinal barrier in the retinas of mice with DR. We demonstrated that GEN was capable of protecting Müller cells and mice from HG-induced oxidative stress and inflammation, which is mostly dependent on the Nrf2 signaling pathway through GLP-1R. GEN may be an effective approach for the treatment of DR.

scholarly journals A2AR Antagonists Upregulate Expression of GS and GLAST in Rat Hypoxia Model

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jun Yu ◽  
Yan Yan ◽  
Yiye Chen ◽  
Yan Zheng ◽  
Xiaoyan Yu ◽  
...  
Keyword(s):  
Müller Cells ◽  
Muller Cells ◽  
Cell Viability Assay ◽  
Hypoxic Conditions ◽  
Viability Assay ◽  
Drug Concentrations ◽  
A Cell ◽  
Short Time

Background. The aim of this study was to research the effects of glutamine synthetase (GS) and glutamate aspartate transporter (GLAST) in rat Müller cells and the effects of an adenosine A2AR antagonist (SCH 442416) on GS and GLAST in hypoxia both in vivo and in vitro. Methods. This study used RT-PCR and Western blotting to quantify the expressions of GS and GLAST under different hypoxic conditions as well as the expressions of GS and GLAST at different drug concentrations. A cell viability assay was used to assess drug toxicity. Results. mRNA and protein expression of GS and GLAST in hypoxia Group 24 h was significantly increased. mRNA and protein expressions of GS and GLAST both increased in Group 1 μM SCH 442416 compared with other groups. One micromolar SCH 442416 could upregulate GS and GLAST’s activity in hypoxia both in vivo and in vitro. Conclusions. Hypoxia activates GS and GLAST in rat retinal Müller cells in a short time in vitro. (2) A2AR antagonists upregulate the activity of GS and GLAST in hypoxia both in vivo and in vitro.

scholarly journals Dietary compounds as potential modulators of microRNA expression in psoriasis

2019 ◽  
Vol 10 ◽  
pp. 204062231986480 ◽  
Author(s):  
Hristina Kocic ◽  
Giovanni Damiani ◽  
Bojana Stamenkovic ◽  
Michael Tirant ◽  
Andrija Jovic ◽  
...  
Keyword(s):  
Vitamin D ◽  
Omega 3 ◽  
Experimental Conditions ◽  
Keratinocyte Proliferation ◽  
Methyl Donors ◽  
Beneficial Effects ◽  
Small Noncoding Rnas ◽  
The Impact

Nutrigenomic DNA reprogramming in different chronic diseases and cancer has been assessed through the stimulation of gene expression and mRNA synthesis versus DNA silencing by CpG DNA modification (methylation); histone modification (acetylation, methylation) and expression of small noncoding RNAs, known as microRNAs (miRNAs). With regard to the specific nutrigenomic effects in psoriasis, the influence of specific diets on inflammatory cell signaling transcriptional factors such as nuclear factor (NF)-κB and Wnt signaling pathways, on disease-related specific cytokine expression, pro/antioxidant balance, keratinocyte proliferation/apoptosis and on proliferation/differentiation ratio have been documented; however, the influence of dietary compounds on the balance between ‘good and bad’ miRNA expression has not been considered. This review aims to summarize knowledge about aberrant microRNAs expression in psoriasis and to emphasize the potential impact of some dietary compounds on endogenous miRNA synthesis in experimental conditions in vivo and in vitro. Among the aberrantly expressed miRNAs in psoriasis, one of the most prominently upregulated seems to be miR-21. The beneficial effects of phenolic compounds (curcumin and resveratrol), vitamin D, methyl donors, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) are discussed. Highly expressed miR-155 has been downregulated by flavonoids (through a quercetin-rich diet) and by vitamin D. Quercetin has been effective in modulating miR-146a. On the other hand, downregulated miR-125b expression was restored by vitamin D, Coenzyme Q10 and by microelement selenium. In conclusion, the miRNA profile, together with other ‘omics’, may constitute a multifaceted approach to explore the impact of diet on psoriasis prevention and treatment.

scholarly journals Insight into the Influence of Cultivar Type, Cultivation Year, and Site on the Lignans and Related Phenolic Profiles, and the Health-Promoting Antioxidant Potential of Flax (Linum usitatissimum L.) Seeds

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2636 ◽  
Author(s):  
Laurine Garros ◽  
Samantha Drouet ◽  
Cyrielle Corbin ◽  
Cédric Decourtil ◽  
Thibaud Fidel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Biological Activities ◽  
Yeast Cells ◽  
In Vivo Studies ◽  
Major Influence ◽  
Antioxidant Power ◽  
Accumulation Pattern ◽  
The Impact

Flaxseeds are a functional food representing, by far, the richest natural grain source of lignans, and accumulate substantial amounts of other health beneficial phenolic compounds (i.e., flavonols, hydroxycinnamic acids). This specific accumulation pattern is related to their numerous beneficial effects on human health. However, to date, little data is available concerning the relative impact of genetic and geographic parameters on the phytochemical yield and composition. Here, the major influence of the cultivar over geographic parameters on the flaxseed phytochemical accumulation yield and composition is evidenced. The importance of genetic parameters on the lignan accumulation was further confirmed by gene expression analysis monitored by RT-qPCR. The corresponding antioxidant activity of these flaxseed extracts was evaluated, both in vitro, using ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and iron chelating assays, as well as in vivo, by monitoring the impact of UV-induced oxidative stress on the lipid membrane peroxidation of yeast cells. Our results, both the in vitro and in vivo studies, confirm that flaxseed extracts are an effective protector against oxidative stress. The results point out that secoisolariciresinol diglucoside, caffeic acid glucoside, and p-coumaric acid glucoside are the main contributors to the antioxidant capacity. Considering the health benefits of these compounds, the present study demonstrates that the flaxseed cultivar type could greatly influence the phytochemical intakes and, therefore, the associated biological activities. We recommend that this crucial parameter be considered in epidemiological studies dealing with flaxseeds.

scholarly journals Gallic acid enhances reproductive function by modulating oxido-inflammatory and apoptosis mediators in rats exposed to aflatoxin-B1

2020 ◽  
Vol 245 (12) ◽  
pp. 1016-1028 ◽  
Author(s):  
Solomon E Owumi ◽  
Isaac A Adedara ◽  
Ayomide P Akomolafe ◽  
Ebenezer O Farombi ◽  
Adegboyega K Oyelere
Keyword(s):  
Oxidative Stress ◽  
Gallic Acid ◽  
Aflatoxin B1 ◽  
Reproductive Function ◽  
Interleukin 10 ◽  
Antioxidant Defenses ◽  
The Impact ◽  
Hormonal Levels

Aflatoxin B1 (AFB1) is reported to elicit adverse reproductive outcomes in animals. Gallic acid (GA) is known to exhibit antioxidant and inflammatory bioactivities. The impact of GA on AFB1-facilitated reproductive dysfunction is nonexistent in literature. This investigation elucidated GA protective effect on AFB1-induced reproductive toxicities in rats, exposed for 28 consecutive days to AFB1 (75 µg/kg), or co-treated with GA (20 or 40 mg/kg) body weight. AFB1 significantly (p  <  0.05) reduced testicular function biomarkers, serum hormonal levels, and functional sperm characteristics in experimental animals. GA abated AFB1-induced increases (p  <  0.05) in lipid peroxidation and reactive oxygen and nitrogen species, suppressed myeloperoxidase, interleukin-1β, nitric oxide, and tumor necrosis factor-α levels—inflammatory biomarkers—in testes, epididymis, and hypothalamus. Furthermore, GA improved antioxidant defenses and alleviated reduction in interleukin-10, caspase-3 activation, and histological variations in epididymis, testes, and hypothalamus of rats dosed with AFB1. Conclusively, GA enhanced reproductive function in AFB1-exposed rats by modulating inflammatory, oxidative stress, and apoptosis mediators. Impact statement Infertility resulting from reproductive deficiency can be stressful. Exposure to aflatoxin B1, a dietary mycotoxin prevalent in improperly stored grains, is reported to elicit reproductive insufficiencies and infertility. We, therefore, examined the likely beneficial effect of gallic acid (GA) a phytochemical, recognized to exhibit in vitro and in vivo pharmacological bioactivities against oxidative stress and related inflammatory damages in rats, since AFB1 toxicities are predicated on oxidative epoxide formation, in a bid to proffer new evidence to advance the field of nutriceutical application from plant-derived chemopreventive agents. Our findings will advance the field of chemoprevention by presenting data absent in the literature on GA. Our results demonstrate further evidence for GA conferred protection against AFB1-mediated histological lesions in testes, epididymis, and hypothalamus of treated rats; suppresses oxidative damages, relieved inflammatory and apoptotic responses, restored sperm functional characteristics, and hormonal levels relevant for reproductive integrity and function.

scholarly journals (Pro)renin receptor involves in myocardial fibrosis and oxidative stress in diabetic cardiomyopathy via the PRR–YAP pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shiran Yu ◽  
Xuefei Dong ◽  
Min Yang ◽  
Qingtao Yu ◽  
Jie Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Fibrosis ◽  
Cardiac Fibroblasts ◽  
Animal Experiments ◽  
Specific Inhibitor ◽  
Neonatal Rat ◽  
Rnai Silencing ◽  
The Impact

Abstract(Pro)renin receptor (PRR) and Yes-associated protein (YAP) play an important role in cardiovascular diseases. However, the role of PRR–YAP pathway in the pathogenesis of DCM is also not clear. We hypothesized that PRR–YAP pathway may promote pathological injuries in DCM by triggering redox. Wistar rats and neonatal rat cardiac fibroblasts were respectively used in vivo and in vitro studies. In order to observe the effects of PRR mediated YAP pathway on the pathogenesis of DCM, animal experiments were divided into 3 parts, including the evaluation the effects of PRR overexpression, PRR RNAi silencing and YAP RNAi silencing. Recombinant-adenoviruses-carried-PRR-gene (Ad-PRR), Ad-PRR-shRNA and lentivirus-carried-YAP-shRNA were constructed and the effects of PRR mediated YAP on the pathogenesis of DCM were evaluated. YAP specific inhibitor Verteporfin was also administrated in cardiac fibroblasts to explore the impact of PRR–YAP pathway on oxidative stress and myocardial fibrosis. The results displayed that PRR overexpression could enhance YAP expression but PRR RNAi silencing down-regulated its expression. Moreover, PRR overexpression could exacerbate oxidative stress and myocardial fibrosis in DCM, and these pathological changes could be rescued by YAP blockade. We concluded that PRR–YAP pathway plays a key role in the pathogenesis of DCM.

scholarly journals 670nm photobiomodulation modulates bioenergetics and oxidative stress, in rat Müller cells challenged with high glucose

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260968
Author(s):  
Hannah J. Nonarath ◽  
Alexandria E. Hall ◽  
Gopika SenthilKumar ◽  
Betsy Abroe ◽  
Janis T. Eells ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Glial Cells ◽  
High Glucose ◽  
Near Infrared ◽  
Müller Cells ◽  
Model System ◽  
Light Treatment ◽  
Muller Cells ◽  
Müller Glial Cells

Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is associated with oxidative stress, nuclear factor-κB (NFκB) activation, and excess production of vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1). Muller glial cells, spanning the entirety of the retina, are involved in DR inflammation. Mitigation of DR pathology currently occurs via invasive, frequently ineffective therapies which can cause adverse effects. The application of far-red to near-infrared (NIR) light (630-1000nm) reduces oxidative stress and inflammation in vitro and in vivo. Thus, we hypothesize that 670nm light treatment will diminish oxidative stress preventing downstream inflammatory mechanisms associated with DR initiated by Muller cells. In this study, we used an in vitro model system of rat Müller glial cells grown under normal (5 mM) or high (25 mM) glucose conditions and treated with a 670 nm light emitting diode array (LED) (4.5 J/cm2) or no light (sham) daily. We report that a single 670 nm light treatment diminished reactive oxygen species (ROS) production and preserved mitochondrial integrity in this in vitro model of early DR. Furthermore, treatment for 3 days in culture reduced NFκB activity to levels observed in normal glucose and prevented the subsequent increase in ICAM-1. The ability of 670nm light treatment to prevent early molecular changes in this in vitro high glucose model system suggests light treatment could mitigate early deleterious effects modulating inflammatory signaling and diminishing oxidative stress.

scholarly journals Neural Oxidant-stress by Azadirachtin Induces Anti-oxidative Enzymes Evincing Biomarker Potential in Paddy Pest, Spathosternum prasiniferum prasiniferum (Orthoptera:Acridoidea)

2019 ◽  
pp. 1-10
Author(s):  
Balaram Manna ◽  
Smarajit Maiti ◽  
Amlan Das
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Growth Regulation ◽  
Oxidant Stress ◽  
Oxidative Enzymes ◽  
Oxidative Stress Marker ◽  
Stress Marker ◽  
The Impact

Azadirachtin (C35H44O16/AZT) develops antifeedancy/growth-regulation/fecundity-suppression/ sterilization/oviposition/repellence and deformity in insect via biochemical/cellular changes and causes their death. Agricultural productivity/quality/eco-sustainability is concerned to this issue. ROS are cytotoxic-factors generated in invertebrates in stress-conditions. The present in-vivo/in-vitro study aimed to investigate the impact of dose dependant AZT toxicity on oxidative-stress-marker (alkaline-phosphatise/ALP; thiobarbituric-acid-reactive-substances/TBARS; non-protein-soluble-thiols/NPSH; acetyl-cholinesterase/AChE) and antioxidant-enzyme activity (superoxide-dismutase/SOD; catalase/CAT; glutathione-peroxidise/GPx; amylase) in brain/hemolymph of Spathosternum prasiniferum prasiniferum (Walker,1871) (Orthoptera:Acridoidea). Acridids are highly abundant and bio-indicator of grassland-ecosystem. During cultivation, insects are exposed (dose/time dependant) to AZT. AZT developed restlessness, jerky-movements and swarming-movements in the insects. It promoted oxidative-stress-marker in brain/hemolymphin both sexes but female had significantly stimulated antioxidant-enzymes to overcome cellular-stress. Increase of brain TBARS, antioxidant-enzymes and decrease in NPSH by AZT indicates oxidative-stress induction in this species. In several instances damage to the brain DNA was noticed. In general female insect responded more intensely with some prominent adaptive strategies.

scholarly journals Reprogramming of endogenous Müller cells into photoreceptor-like cells induced by small-molecule compounds in mice

2021 ◽  
Author(s):  
Yuya Fujii ◽  
Mitsuru Arima ◽  
Yusuke Murakami ◽  
Koh-Hei Sonoda
Keyword(s):  
Intravitreal Injection ◽  
Small Molecule ◽  
Messenger Rna ◽  
Glycogen Synthase ◽  
Müller Cells ◽  
Photoreceptor Cells ◽  
Lineage Tracing ◽  
Muller Cells

Abstract Lifelong visual impairment occurs from retinal diseases due to the inability of photoreceptor cells to regenerate in mammals. We demonstrated that endogenous Müller cells (MCs) in mice differentiate into photoreceptor-like cells by intravitreal injection of four small-molecule compounds: tumor growth factor-β inhibitor, bone morphogenetic protein inhibitor, glycogen synthase kinase 3 inhibitor, and γ-secretase inhibitor. In vitro, the messenger RNA of rhodopsin (Rho) in MCs increased 30-fold, and 25% of cultured MCs expressed Rho protein 7 days after stimulation with these compounds. In vivo, Rho-positive cells were regenerated on day 7 after the intravitreal injection of four compounds, accompanied with recovery of Rho-derived scotopic function. Lineage tracing in mice treated with N-methyl-N-nitrosourea, a disease model of photoreceptor degeneration, showed that the regenerated Rho-positive cells were originated from endogenous MCs. Finally, the regeneration of Rho-positive cells was also induced in the retina of rd10 mice, a model with similar genetic mutation as humans. Notably, the intravitreal injection significantly reduced cone cell death in rd10 mice. This treatment could be a new strategy in retinal regenerative medicine where mammalian endogenous MCs are reprogrammed into photoreceptor cells independent of transplantation or gene transfer.

scholarly journals Neither Excessive Nitric Oxide Accumulation nor Acute Hyperglycemia Affects the N-Acetylaspartate Network in Wistar Rat Brain Cells

2020 ◽  
Vol 21 (22) ◽  
pp. 8541
Author(s):  
Marlena Zyśk ◽  
Piotr Pikul ◽  
Robert Kowalski ◽  
Krzysztof Lewandowski ◽  
Monika Sakowicz-Burkiewicz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Wistar Rat ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Male Adult ◽  
The Impact

The N-acetylaspartate network begins in neurons with N-acetylaspartate production catalyzed by aspartate N-acetyltransferase from acetyl-CoA and aspartate. Clinical studies reported a significant depletion in N-acetylaspartate brain level in type 1 diabetic patients. The main goal of this study was to establish the impact of either hyperglycemia or oxidative stress on the N-acetylaspartate network. For the in vitro part of the study, embryonic rat primary neurons were treated by using a nitric oxide generator for 24 h followed by 6 days of post-treatment culture, while the neural stem cells were cultured in media with 25–75 mM glucose. For the in vivo part, male adult Wistar rats were injected with streptozotocin (65 mg/kg body weight, ip) to induce hyperglycemia (diabetes model) and euthanized 2 or 8 weeks later. Finally, the biochemical profile, NAT8L protein/Nat8l mRNA levels and enzymatic activity were analyzed. Ongoing oxidative stress processes significantly affected energy metabolism and cholinergic neurotransmission. However, the applied factors did not affect the N-acetylaspartate network. This study shows that reduced N-acetylaspartate level in type 1 diabetes is not related to oxidative stress and that does not trigger N-acetylaspartate network fragility. To reveal why N-acetylaspartate is reduced in this pathology, other processes should be considered.

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