scholarly journals 2,3,4′,5-Tetrahydroxystilbene-2-O-β-D-Glucoside (THSG) Activates the Nrf2 Antioxidant Pathway and Attenuates Oxidative Stress-Induced Cell Death in Mouse Cochlear UB/OC-2 Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 465 ◽  
Author(s):  
Tien-Yuan Wu ◽  
Jia-Ni Lin ◽  
Zi-Yao Luo ◽  
Chuan-Jen Hsu ◽  
Jen-Shu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Morphological Changes ◽  
Critical Role ◽  
Free Radical Scavenger ◽  
Ros Generation ◽  
Radical Scavenger ◽  
Protective Mechanism ◽  
Related Factor ◽  
Detoxifying Enzymes

Oxidative stress plays a critical role in the pathogenesis of hearing loss, and 2,3,4′,5-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) exerts antioxidant effects by inhibiting reactive oxygen species (ROS) generation. With the aim of developing new therapeutic strategies for oxidative stress, this study investigated the protective mechanism of THSG in vitro using a normal mouse cochlear cell line (UB/OC-2). The THSG and ascorbic acid have similar free radical scavenger capacities. H2O2, but not THSG, reduced the UB/OC-2 cell viability. Moreover, H2O2 might induce apoptosis and autophagy by inducing morphological changes, as visualized by microscopy. As evidenced by Western blot analysis and monodansylcadaverine (MDC) staining, THSG might decrease H2O2-induced autophagy. According to a Western blotting analysis and Annexin V/PI and JC-1 staining, THSG might protect cells from H2O2-induced apoptosis and stabilize the mitochondrial membrane potential. Furthermore, THSG enhanced the translocation of nucleus factor erythroid 2-related factor 2 (Nrf2) into the nucleus and increased the mRNA and protein expression of antioxidant/detoxifying enzymes under H2O2-induced oxidative stress conditions. Collectively, our findings demonstrate that THSG, as a scavenging agent, can directly attenuate free radicals and upregulate antioxidant/detoxifying enzymes to protect against oxidative damage and show that THSG protects UB/OC-2 cells from H2O2-induced autophagy and apoptosis in vitro.

scholarly journals Immunohistochemical Study of Nrf2-Antioxidant Response Element as Indicator of Oxidative Stress Induced by Cadmium in Developing Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Sergio Montes ◽  
Daniel Juárez-Rebollar ◽  
Concepción Nava-Ruíz ◽  
Aurora Sánchez-García ◽  
Yesica Heras-Romero ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Morphological Changes ◽  
Antioxidant Response ◽  
Protective Mechanism ◽  
Antioxidant Response Element ◽  
Response Element ◽  
Expression Of Genes ◽  
Old Rats ◽  
Kidney Liver

In developing animals, Cadmium (Cd) induces toxicity to many organs including brain. Reactive oxygen species (ROS) are often implicated in Cd-inducedtoxicity and it has been clearly demonstrated that oxidative stress interferes with the expression of genes as well as transcriptional factors such as Nrf2-dependent Antioxidant Response Element (Nrf2-ARE). Cd-generated oxidative stress and elevated Nrf2 activity have been reportedin vitroandin situcells. In this study we evaluated the morphological changes and the expression pattern of Nrf2 and correlated them with the Cd concentrations in different ages of developing rats in heart, lung, kidney, liver, and brain. The Cd content in different organs of rats treated with the metal was increased in all ages assayed. Comparatively, lower Cd brain levels were found in rats intoxicated at the age of 12 days, then pups treated at 5, 10, or 15 days old, at the same metal dose. No evident changes, as a consequence of cadmium exposure, were evident in the morphological analysis in any of the ages assayed. However, Nrf2-ARE immunoreactivity was observed in 15-day-old rats exposed to Cd. Our results support that fully developed blood-brain barrier is an important protector against Cd entrance to brain and that Nrf2 increased expression is a part of protective mechanism against cadmium-induced toxicity.

scholarly journals Day and Night GSH and MDA Levels in Healthy Adults and Effects of Different Doses of Melatonin on These Parameters

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Shilpa Chakravarty ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Membrane Lipid ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Secretory Product ◽  
Therapeutic Implications ◽  
Antioxidative Function ◽  
Reliable Marker

The pineal secretory product melatonin (chemically, N-acetyl-5-methoxytryptamine) acts as an effective antioxidant and free-radical scavenger and plays an important role in several physiological functions such as sleep induction, immunomodulation, cardiovascular protection, thermoregulation, neuroprotection, tumor-suppression and oncostasis. Membrane lipid-peroxidation in terms of malondialdehyde (MDA) and intracellular glutathione (GSH) is considered to be a reliable marker of oxidative stress. The present work was undertaken to study the modulating effect of melatonin on MDA and GSH in human erythrocytes during day and night. Our observation shows the modulation of these two biomarkers by melatonin, and this may have important therapeutic implications.In vitrodose-dependent effect of melatonin also showed variation during day and night. We explain our observations on the basis of melatonin's antioxidative function and its effect on the fluidity of plasma membrane of red blood cells. Rhythmic modulation of MDA and GSH contents emphasized the role of melatonin as an antioxidant and its function against oxidative stress.

scholarly journals Neuroprotective effect of a new free radical scavenger HL-008 against ischemia-reperfusion injury

2020 ◽  
Author(s):  
Yahong Liu ◽  
Ying Cheng ◽  
Wei Zhang ◽  
Hongqi Tian
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Brain Tissue ◽  
Cell Activation ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Radical Scavenger

Abstract Oxidative stress plays a critical role in cerebral ischemia-reperfusion injury. We previously developed a powerful antioxidant, HL-008, and this study aimed to investigate the neuroprotective function of HL-008. The in vitro and in vivo efficacy of HL-008 was evaluated using a PC-12 cell oxidative stress model induced by hydrogen peroxide and a rat model of middle cerebral artery occlusion, respectively. The MTT assay was used to analyze cell viability. TTC staining, HE staining, immunofluorescence, western blot, and proteomics were used to evaluate the infarction volume, brain tissue morphology, apoptosis, inflammation, and related pathways. Indicators related to oxidative levels were mainly detected using commercial kits. HL-008 significantly reduced the cerebral infarction area induced by ischemia-reperfusion, improved the neurological score, alleviated oxidative stress and inflammation in the brain tissue, reduced glial cell activation, inhibited brain tissue apoptosis by influencing multiple signaling pathways, and had a neuroprotective effect. If HL-008 is successfully developed, it can significantly improve the quality of life of stroke patients.

scholarly journals Lactobacillus plantarum Exhibits Antioxidant and Cytoprotective Activities in Porcine Intestinal Epithelial Cells Exposed to Hydrogen Peroxide

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jing Wang ◽  
Wei Zhang ◽  
Sixin Wang ◽  
Yamin Wang ◽  
Xu Chu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Epithelial Cells ◽  
Lactobacillus Plantarum ◽  
Redox Homeostasis ◽  
Critical Role ◽  
Probiotic Bacterium ◽  
Related Factor ◽  
H2o2 Treatment

Probiotics are widely used for protection against stress-induced intestinal dysfunction. Oxidative stress plays a critical role in gastrointestinal disorders. It is established that probiotics alleviate oxidative stress; however, the mechanism of action has not been elucidated. We developed an in vitro intestinal porcine epithelial cells (IPEC-J2) model of oxidative stress to explore the antioxidant effect and potential mode of action of Lactobacillus plantarum ZLP001. The IPEC-J2 cells were preincubated with and without L. plantarum ZLP001 for 3 h and then exposed to hydrogen peroxide (H2O2) for 4 h. Pretreatment with L. plantarum ZLP001 protected IPEC-J2 cells against H2O2-induced oxidative damage as indicated by cell viability assays and significantly alleviated apoptosis elicited by H2O2. L. plantarum ZLP001 pretreatment decreased reactive oxygen species production and the cellular malondialdehyde concentration and increased the mitochondrial membrane potential compared with H2O2 treatment alone, suggesting that L. plantarum ZLP001 promotes the maintenance of redox homeostasis in the cells. Furthermore, L. plantarum ZLP001 regulated the expression and generation of some antioxidant enzymes, thereby activating the antioxidant defense system. Treatment with L. plantarum ZLP001 led to nuclear erythroid 2-related factor 2 (Nrf2) enrichment in the nucleus compared with H2O2 treatment alone. Knockdown of Nrf2 significantly weakened the alleviating effect of L. plantarum ZLP001 on antioxidant stress in IPEC-J2 cells, suggesting that Nrf2 is involved in the antioxidative effect of L. plantarum ZLP001. Collectively, these results indicate that L. plantarum ZLP001 is a promising probiotic bacterium that can potentially alleviate oxidative stress.

scholarly journals Carnosic Acid Attenuates Cadmium Induced Nephrotoxicity by Inhibiting Oxidative Stress, Promoting Nrf2/HO-1 Signalling and Impairing TGF-β1/Smad/Collagen IV Signalling

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4176 ◽  
Author(s):  
Sonjit Das ◽  
Saikat Dewanjee ◽  
Tarun K. Dua ◽  
Swarnalata Joardar ◽  
Pratik Chakraborty ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Collagen Iv ◽  
Carnosic Acid ◽  
Protective Mechanism ◽  
Related Factor ◽  
Renal Cells ◽  
Cdcl2 Treatment ◽  
Tgf Β1

Cadmium (Cd) imparts nephrotoxicity via triggering oxidative stress and pathological signal transductions in renal cells. The present study was performed to explore the protective mechanism of carnosic acid (CA), a naturally occurring antioxidant compound, against cadmium chloride (CdCl2)-provoked nephrotoxicity employing suitable in vitro and in vivo assays. CA (5 µM) exhibited an anti-apoptotic effect against CdCl2 (40 µM) in normal kidney epithelial (NKE) cells evidenced from cell viability, image, and flow cytometry assays. In this study, CdCl2 treatment enhanced oxidative stress by triggering free radical production, suppressing the endogenous redox defence system, and inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) activation in NKE cells and mouse kidneys. Moreover, CdCl2 treatment significantly endorsed apoptosis and fibrosis via activation of apoptotic and transforming growth factor (TGF)-β1/mothers against decapentaplegic homolog (Smad)/collagen IV signalling pathways, respectively. In contrast, CA treatment significantly attenuated Cd-provoked nephrotoxicity via inhibiting free radicals, endorsing redox defence, suppressing apoptosis, and inhibiting fibrosis in renal cells in both in vitro and in vivo systems. In addition, CA treatment significantly (p < 0.05–0.01) restored blood and urine parameters to near-normal levels in mice. Histological findings further confirmed the protective role of CA against Cd-mediated nephrotoxicity. Molecular docking predicted possible interactions between CA and Nrf2/TGF-β1/Smad/collagen IV. Hence, CA was found to be a potential therapeutic agent to treat Cd-mediated nephrotoxicity.

scholarly journals Andrographolide Ameliorates Diabetic Cardiomyopathy in Mice by Blockage of Oxidative Damage and NF-κB-Mediated Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Ershun Liang ◽  
Xue Liu ◽  
Zhanhui Du ◽  
Ruixue Yang ◽  
Yuxia Zhao
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Therapeutic Potential ◽  
Myocardial Dysfunction ◽  
Underlying Mechanism ◽  
Ros Generation ◽  
Related Factor

Andrographolide (Andro), a major bioactive component obtained from Andrographis paniculata Nees, has exerted wide antioxidant as well as cytoprotective properties. However, whether Andro treatment could retard the progress of diabetic cardiomyopathy (DCM) remains unknown. In this study, we evaluated the effects of Andro against diabetes-induced myocardial dysfunction and explored the underlying mechanism in STZ-induced diabetic mice. As a result, treatment with Andro dose dependently suppressed cardiac inflammation and oxidative stress, accompanied by decreasing cardiac apoptosis, which subsequently ameliorated cardiac fibrosis and cardiac hypertrophy. Further, Andro blocked hyperglycemia-triggered reactive oxygen species (ROS) generation by suppressing NADPH oxidase (NOX) activation and augmenting nuclear factor erythroid 2-related factor 2 (Nrf2) expression both in vitro and in vivo. Our results suggest that the cardioprotective effects afforded by Andro treatment involve the modulation of NOX/Nrf2-mediated oxidative stress and NF-κB-mediated inflammation. The present study unravels the therapeutic potential of Andro in the treatment of DCM by attenuating oxidative stress, inflammation, and apoptosis.

scholarly journals Ethyl Vanillin Protects against Kidney Injury in Diabetic Nephropathy by Inhibiting Oxidative Stress and Apoptosis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yuna Tong ◽  
Shan Liu ◽  
Rong Gong ◽  
Lei Zhong ◽  
Xingmei Duan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Cell Apoptosis ◽  
Cell Model ◽  
Critical Role ◽  
Kidney Injury ◽  
Related Factor ◽  
Ethyl Vanillin

Diabetes-induced oxidative stress and apoptosis is regarded as a critical role in the pathogenesis of diabetic nephropathy (DN). Treating diabetes-induced kidney damage and renal dysfunction has been thought a promising therapeutic option to attenuate the development and progression of DN. In this study, we investigated the renoprotective effect of ethyl vanillin (EVA), an active analogue of vanillin isolated from vanilla beans, on streptozotocin- (STZ-) induced rat renal injury model and high glucose-induced NRK-52E cell model. The EVA treatment could strongly improve the deterioration of renal function and kidney cell apoptosis in vivo and in vitro. Moreover, treating with EVA significantly decreased the level of MDA and reactive oxygen species (ROS) and stabilized antioxidant enzyme system in response to oxidative stress by enhancing the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in vivo and in vitro. Furthermore, EVA also markedly suppressed cleaved caspase-3, Bax, and nuclear transcription factor erythroid 2-related factor (Nrf2) expression in STZ-induced rats. Therefore, these results of our investigation provided that EVA might protect against kidney injury in DN by inhibiting oxidative stress and cell apoptosis.

scholarly journals Fasting Drives Nrf2-Related Antioxidant Response in Skeletal Muscle

2020 ◽  
Vol 21 (20) ◽  
pp. 7780
Author(s):  
Daniele Lettieri-Barbato ◽  
Giuseppina Minopoli ◽  
Rocco Caggiano ◽  
Rossella Izzo ◽  
Mariarosaria Santillo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Energy Homeostasis ◽  
Antioxidant Response ◽  
Protective Mechanism ◽  
Related Factor ◽  
Adaptive Responses ◽  
Positive Role

A common metabolic condition for living organisms is starvation/fasting, a state that could play systemic-beneficial roles. Complex adaptive responses are activated during fasting to help the organism to maintain energy homeostasis and avoid nutrient stress. Metabolic rearrangements during fasting cause mild oxidative stress in skeletal muscle. The nuclear factor erythroid 2-related factor 2 (Nrf2) controls adaptive responses and remains the major regulator of quenching mechanisms underlying different types of stress. Here, we demonstrate a positive role of fasting as a protective mechanism against oxidative stress in skeletal muscle. In particular, by using in vivo and in vitro models of fasting, we found that typical Nrf2-dependent genes, including those controlling iron (e.g., Ho-1) and glutathione (GSH) metabolism (e.g., Gcl, Gsr) are induced along with increased levels of the glutathione peroxidase 4 (Gpx4), a GSH-dependent antioxidant enzyme. These events are associated with a significant reduction in malondialdehyde, a well-known by-product of lipid peroxidation. Our results suggest that fasting could be a valuable approach to boost the adaptive anti-oxidant responses in skeletal muscle.

scholarly journals The link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction

2016 ◽  
Vol 9 (1) ◽  
pp. 11-27 ◽  
Author(s):  
Karl-Erik Andersson ◽  
Donna B. Boedtkjer ◽  
Axel Forman
Keyword(s):  
Oxidative Stress ◽  
Bladder Dysfunction ◽  
Morphological Changes ◽  
Pde5 Inhibitor ◽  
Bladder Wall ◽  
Radical Scavenger ◽  
Chronic Ischemia ◽  
Arterial Insufficiency ◽  
Bladder Ischemia

The vascular supply to the human bladder is derived mainly from the superior and inferior vesical arteries, the latter being directly connected to the internal iliac artery. Aging is associated with an impairment of blood vessel function and changes may occur in the vasculature at the molecular, cellular and functional level. Pelvic arterial insufficiency may play an important role in the development of bladder dysfunctions such as detrusor overactivity (DO) and the overactive bladder syndrome. Chronic ischemia-related bladder dysfunction may progress to bladder underactivity and it would be desirable to treat not only lower urinary tract symptoms (LUTS) induced by chronic ischemia, but also the progression of the morphological bladder changes. Studies in experimental models in rabbits and rats have shown that pelvic arterial insufficiency may result in significant bladder ischemia with reduced bladder wall oxygen tension. In turn, this will lead to oxidative stress associated with upregulation of oxidative stress-sensitive genes, increased muscarinic receptor activity, ultrastructural damage, and neurodegeneration. The phosphodiesterase type 5 (PDE5) inhibitor tadalafil, the α1-adrenoceptor (AR) blocker silodosin, the β3-AR agonist mirabegron, and the free radical scavenger melatonin, exerted a protecting effect on urodynamic parameters, and on functional and morphological changes of the bladder demonstrable in vitro. Since the agents tested are used clinically for relieving LUTS, the results from the animal models seem to have translational value, and may be of relevance for designing clinical studies to demonstrate if the drugs may prevent progression of ischemia-related functional and morphological bladder changes.

scholarly journals Therapeutic Modulation of Virus-Induced Oxidative Stress via the Nrf2-Dependent Antioxidative Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-26 ◽  
Author(s):  
Choongho Lee
Keyword(s):  
Oxidative Stress ◽  
Host Response ◽  
Critical Role ◽  
Viral Diseases ◽  
Ros Generation ◽  
Related Factor ◽  
Defense System ◽  
Front Line ◽  
Nrf2 Pathway ◽  
Pharmacological Manipulations

Virus-induced oxidative stress plays a critical role in the viral life cycle as well as the pathogenesis of viral diseases. In response to reactive oxygen species (ROS) generation by a virus, a host cell activates an antioxidative defense system for its own protection. Particularly, a nuclear factor erythroid 2p45-related factor 2 (Nrf2) pathway works in a front-line for cytoprotection and detoxification. Recently, a series of studies suggested that a group of clinically relevant viruses have the capacity for positive and negative regulations of the Nrf2 pathway. This virus-induced modulation of the host antioxidative response turned out to be a crucial determinant for the progression of several viral diseases. In this review, virus-specific examples of positive and negative modulations of the Nrf2 pathway will be summarized first. Then a number of successful genetic and pharmacological manipulations of the Nrf2 pathway for suppression of the viral replication and the pathogenesis-associated oxidative damage will be discussed later. Understanding of the interplay between virus-induced oxidative stress and antioxidative host response will aid in the discovery of potential antiviral supplements for better management of viral diseases.

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