scholarly journals Rosmarinic Acid Alleviates the Endothelial Dysfunction Induced by Hydrogen Peroxide in Rat Aortic Rings via Activation of AMPK

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Hui Zhou ◽  
Baocai Fu ◽  
Bo Xu ◽  
Xiangquan Mi ◽  
Gang Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Endothelial Dysfunction ◽  
Rosmarinic Acid ◽  
Dependent Manner ◽  
Vascular Events ◽  
Concentration Dependent Manner ◽  
Obvious Effect ◽  
Beneficial Effects ◽  
Compound C

Endothelial dysfunction is the key player in the development and progression of vascular events. Oxidative stress is involved in endothelial injury. Rosmarinic acid (RA) is a natural polyphenol with antioxidative, antiapoptotic, and anti-inflammatory properties. The present study investigates the protective effect of RA on endothelial dysfunction induced by hydrogen peroxide (H2O2). Compared with endothelium-denuded aortic rings, the endothelium significantly alleviated the decrease of vasoconstrictive reactivity to PE and KCl induced by H2O2. H2O2 pretreatment significantly injured the vasodilative reactivity to ACh in endothelium-intact aortic rings in a concentration-dependent manner. RA individual pretreatment had no obvious effect on the vasoconstrictive reaction to PE and KCl, while its cotreatment obviously mitigated the endothelium-dependent relaxation impairments and the oxidative stress induced by H2O2. The RA cotreatment reversed the downregulation of AMPK and eNOS phosphorylation induced by H2O2 in HAEC cells. The pretreatment with the inhibitors of AMPK (compound C) and eNOS (L-NAME) wiped off RA’s beneficial effects. All these results demonstrated that RA attenuated the endothelial dysfunction induced by oxidative stress by activating the AMPK/eNOS pathway.

scholarly journals Carnosine Decreases PMA-Induced Oxidative Stress and Inflammation in Murine Macrophages

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 281 ◽  
Author(s):  
Giuseppe Caruso ◽  
Claudia G. Fresta ◽  
Annamaria Fidilio ◽  
Fergal O’Donnell ◽  
Nicolò Musso ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Energy State ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Inhibitory Effect ◽  
Nucleoside Triphosphate ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Beneficial Effects

Carnosine is an endogenous dipeptide composed of β-alanine and L-histidine. This naturally occurring molecule is present at high concentrations in several mammalian excitable tissues such as muscles and brain, while it can be found at low concentrations in a few invertebrates. Carnosine has been shown to be involved in different cellular defense mechanisms including the inhibition of protein cross-linking, reactive oxygen and nitrogen species detoxification as well as the counteraction of inflammation. As a part of the immune response, macrophages are the primary cell type that is activated. These cells play a crucial role in many diseases associated with oxidative stress and inflammation, including atherosclerosis, diabetes, and neurodegenerative diseases. In the present study, carnosine was first tested for its ability to counteract oxidative stress. In our experimental model, represented by RAW 264.7 macrophages challenged with phorbol 12-myristate 13-acetate (PMA) and superoxide dismutase (SOD) inhibitors, carnosine was able to decrease the intracellular concentration of superoxide anions (O2−•) as well as the expression of Nox1 and Nox2 enzyme genes. This carnosine antioxidant activity was accompanied by the attenuation of the PMA-induced Akt phosphorylation, the down-regulation of TNF-α and IL-6 mRNAs, and the up-regulation of the expression of the anti-inflammatory mediators IL-4, IL-10, and TGF-β1. Additionally, when carnosine was used at the highest dose (20 mM), there was a generalized amelioration of the macrophage energy state, evaluated through the increase both in the total nucleoside triphosphate concentrations and the sum of the pool of intracellular nicotinic coenzymes. Finally, carnosine was able to decrease the oxidized (NADP+)/reduced (NADPH) ratio of nicotinamide adenine dinucleotide phosphate in a concentration dependent manner, indicating a strong inhibitory effect of this molecule towards the main source of reactive oxygen species in macrophages. Our data suggest a multimodal mechanism of action of carnosine underlying its beneficial effects on macrophage cells under oxidative stress and inflammation conditions.

scholarly journals Artemisinin Attenuated Hydrogen Peroxide (H2O2)-Induced Oxidative Injury in SH-SY5Y and Hippocampal Neurons via the Activation of AMPK Pathway

2019 ◽  
Vol 20 (11) ◽  
pp. 2680 ◽  
Author(s):  
Xia Zhao ◽  
Jiankang Fang ◽  
Shuai Li ◽  
Uma Gaur ◽  
Xingan Xing ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Neurodegenerative Diseases ◽  
Hippocampal Neurons ◽  
Neuronal Cells ◽  
Adenosine Monophosphate ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Concentration Dependent Manner ◽  
Ampk Pathway

Oxidative stress is believed to be one of the main causes of neurodegenerative diseases such as Alzheimer’s disease (AD). The pathogenesis of AD is still not elucidated clearly but oxidative stress is one of the key hypotheses. Here, we found that artemisinin, an anti-malarial Chinese medicine, possesses neuroprotective effects. However, the antioxidative effects of artemisinin remain to be explored. In this study, we found that artemisinin rescued SH-SY5Y and hippocampal neuronal cells from hydrogen peroxide (H2O2)-induced cell death at clinically relevant doses in a concentration-dependent manner. Further studies showed that artemisinin significantly restored the nuclear morphology, improved the abnormal changes in intracellular reactive oxygen species (ROS), reduced the mitochondrial membrane potential, and caspase-3 activation, thereby attenuating apoptosis. Artemisinin also stimulated the phosphorylation of the adenosine monophosphate -activated protein kinase (AMPK) pathway in SH-SY5Y cells in a time- and concentration-dependent manner. Inhibition of the AMPK pathway attenuated the protective effect of artemisinin. These data put together suggested that artemisinin has the potential to protect neuronal cells. Similar results were obtained in primary cultured hippocampal neurons. Cumulatively, these results indicated that artemisinin protected neuronal cells from oxidative damage, at least in part through the activation of AMPK. Our findings support the role of artemisinin as a potential therapeutic agent for neurodegenerative diseases.

Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes

1998 ◽  
Vol 274 (1) ◽  
pp. C245-C252 ◽  
Author(s):  
Junsuke Igarashi ◽  
Masashi Nishida ◽  
Shiro Hoshida ◽  
Nobushige Yamashita ◽  
Hiroaki Kosaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiac Myocytes ◽  
Myocardial Injury ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
No Donor ◽  
Oxide Synthase ◽  
Gpx Activity

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined. Interleukin-1β induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS,l-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso- N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2(0.1 mM, 1 h). Inhibition of iNOS with Nω-nitro-l-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.

scholarly journals Beneficial effects of methanolic extract of Indigofera linnaei Ali. on the inflammatory and nociceptive responses in rodent models

2016 ◽  
Vol 52 (1) ◽  
pp. 113-123
Author(s):  
Raju Senthil Kumar ◽  
Balasubramanian Rajkapoor ◽  
Perumal Perumal ◽  
Sekar Vinoth Kumar ◽  
Arunachalam Suba Geetha
Keyword(s):  
Methanol Extract ◽  
Latency Period ◽  
Dependent Manner ◽  
Rodent Models ◽  
Hot Plate ◽  
Concentration Dependent Manner ◽  
Standard Drug ◽  
Beneficial Effects ◽  
Nociceptive Responses

ABSTRACT Indigofera linnaei Ali. (Tamil Name: Cheppu Nerinjil) belongs to the family Fabaceae, used for the treatment of various ailments in the traditional system of medicine. In the present study, the beneficial effects of methanol extract of whole plant of I. linnaei (MEIL) were evaluated on inflammation and nociception responses in rodent models. In vitro nitric oxide (NO), lipoxygenase (LOX) and cyclooxygense (COX) inhibitory activities were also performed to understand the mode of action. MEIL at the dose of 200 & 400 mg/kg, p.o. significantly inhibited carrageenan induced rat paw volume and reduced the weight of granuloma in cotton pellet granuloma model. The results obtained were comparable with the standard drug aceclofenac. The anti-nociceptive effect of MEIL in mice was evaluated in hot plate and acetic acid induced writhing model. The plant extract significantly reduced the number of writhes and the analgesic effect was higher than that of the standard drug aspirin. However, the extract fails to increase the latency period in hot plate method suggesting that the extract produce nociception by peripheral activity. The extract produced inhibitory effect on NO, LOX and COX in concentration dependent manner. The extract exhibited pronounced and selective COX-2 inhibition. Altogether, these results suggested that the methanol extract of Indigofera linnaei could be considered as a potential anti-inflammatory and analgesic agent.

scholarly journals Oxidative stress increases megalin expression in the renal proximal tubules during the normoalbuminuric stage of diabetes mellitus

2018 ◽  
Vol 314 (3) ◽  
pp. F462-F470 ◽  
Author(s):  
Yoshifumi Kurosaki ◽  
Akemi Imoto ◽  
Fumitaka Kawakami ◽  
Masanori Yokoba ◽  
Tsuneo Takenaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Hydrogen Peroxide ◽  
High Glucose ◽  
Renal Cortex ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphorylated Akt ◽  
Stress Dependent ◽  
Phosphatidylinositol 3

Megalin, an endocytic receptor expressed in proximal tubule cells, plays a critical role in renal tubular protein reabsorption and is associated with the albuminuria observed in diabetic nephropathy. We have previously reported increased oxidant production in the renal cortex during the normoalbuminuric stage of diabetes mellitus (DM); however, the relationship between oxidative stress and renal megalin expression during the normoalbuminuric stage of DM remains unclear. In the present study, we evaluated whether oxidative stress affects megalin expression in the normoalbuminuric stage of DM in a streptozotocin-induced diabetic rat model and in immortalized human proximal tubular cells (HK-2). We demonstrated that increased expression of renal megalin accompanies oxidative stress during the early stage of DM, before albuminuria development. Telmisartan treatment prevented the diabetes-induced elevation in megalin level, possibly through an oxidative stress-dependent mechanism. In HK-2 cells, hydrogen peroxide significantly increased megalin levels in a dose- and time-dependent manner; however, the elevation in megalin expression was decreased following prolonged exposure to severe oxidative stress induced by 0.4 mmol/l hydrogen peroxide. High-glucose treatment also significantly increased megalin expression in HK-2 cells. Concurrent administration of the antioxidant N-acetyl-cysteine blocked the effects of high glucose on megalin expression. Furthermore, the hydrogen peroxide-induced increase in megalin expression was blocked by treatment with phosphatidylinositol 3-kinase and Akt inhibitors. Increase of phosphorylated Akt expression was also seen in the renal cortex of diabetic rats. Taken together, our results indicate that mild oxidative stress increases renal megalin expression through the phosphatidylinositol 3-kinase-Akt pathway in the normoalbuminuric stage of DM.

scholarly journals Effect of Anthocyanin-Rich Extract of Sour Cherry for Hyperglycemia-Induced Inflammatory Response and Impaired Endothelium-Dependent Vasodilation

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3373
Author(s):  
Arnold Markovics ◽  
Attila Biró ◽  
Andrea Kun-Nemes ◽  
Mónika Éva Fazekas ◽  
Anna Anita Rácz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Sour Cherry ◽  
The Elderly ◽  
Human Umbilical Cord ◽  
Dependent Manner

Diabetes mellitus (DM)-related morbidity and mortality are steadily rising worldwide, affecting about half a billion people worldwide. A significant proportion of diabetic cases are in the elderly, which is concerning given the increasing aging population. Proper nutrition is an important component in the effective management of diabetes in the elderly. A plethora of active substances of plant origin exhibit potency to target the pathogenesis of diabetes mellitus. The nutraceutical and pharmaceutical effects of anthocyanins have been extensively studied. In this study, the effect of Hungarian sour cherry, which is rich in anthocyanins, on hyperglycemia-induced endothelial dysfunction was tested using human umbilical cord vein endothelial cells (HUVECs). HUVECs were maintained under both normoglycemic (5 mM) and hyperglycemic (30 mM) conditions with or without two concentrations (1.50 ng/µL) of anthocyanin-rich sour cherry extract. Hyperglycemia-induced oxidative stress and inflammatory response and damaged vasorelaxation processes were investigated by evaluating the level of reactive oxygen species (ROS) and gene expression of four proinflammatory cytokines, namely, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1α (IL-1α), as well as the gene expression of nitric oxide synthase (NOS) endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1). It was found that hyperglycemia-induced oxidative stress was significantly suppressed by anthocyanin-rich sour cherry extract in a concentration-dependent manner. The gene expression of the tested proinflammatory cytokines increased under hyperglycemic conditions but was significantly reduced by both 1 and 50 ng/µL anthocyanin-rich sour cherry extract. Further, although increased ET-1 and ECE-1 expression due to hyperglycemia was reduced by anthocyanin-rich sour cherry extract, NOS expression was increased by the extract. Collectively, these data suggest that anthocyanin-rich sour cherry extract could alleviate hyperglycemia-induced endothelial dysfunction due to its antioxidant, anti-inflammatory, and vasorelaxant effects.

scholarly journals The Protective Effect of Hispidin against Hydrogen Peroxide-Induced Oxidative Stress in ARPE-19 Cells via Nrf2 Signaling Pathway

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 380 ◽  
Author(s):  
Huang ◽  
Chang ◽  
Chau ◽  
Chiu
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Protective Effect ◽  
Retinal Pigment ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Glutamate Cysteine Ligase ◽  
Jnk Pathway ◽  
Nrf2 Signaling Pathway

Hispidin, a polyphenol compound isolated from Phellinus linteus, has been reported to possess antioxidant activities. In this study, we aimed to investigate the mechanisms underlying the protective effect of hispidin against hydrogen peroxide (H2O2)-induced oxidative stress on Adult Retinal Pigment Epithelial cell line-19 (ARPE-19) cells. Hispidin was not cytotoxic to ARPE-19 cells at concentrations of less than 50 μM. The levels of intracellular reactive oxygen species (ROS) were analyzed by dichlorofluorescin diacetate (DCFDA) staining. Hispidin significantly restored H2O2-induced cell death and reduced the levels of intracellular ROS. The expression levels of antioxidant enzymes, such as NAD(P)H:Quinine oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) were examined using real-time PCR and Western blotting. Our results showed that hispidin markedly enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1, NQO-1, GCLM, and GCLC in a dose-dependent manner. Furthermore, knockdown experiments revealed that transfection with Nrf2 siRNA successfully suppresses the hispidin activated Nrf2 signaling in ARPE-19 cells. Moreover, activation of the c-Jun N-terminal kinase (JNK) pathway is involved in mediating the protective effects of hispidin on the ARPE-19 cells. Thus, the present study demonstrated that hispidin provides protection against H2O2-induced damage in ARPE-19 cells via activation of Nrf2 signaling and up-regulation of its downstream targets, including Phase II enzymes, which might be associated with the activation of the JNK pathway.

scholarly journals Antioxidant and Wound Healing Property of Gelsolin in 3T3-L1 Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Bhavna Vaid ◽  
Bhupinder Singh Chopra ◽  
Sachin Raut ◽  
Amin Sagar ◽  
Maulik D. Badmalia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Wound Healing ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Plasma Gelsolin ◽  
Total Antioxidant ◽  
Effective Role ◽  
Healing Property ◽  
Injury Recovery

Delineation of factors which affect wound healing would be of immense value to enable on-time or early healing and reduce comorbidities associated with infections or biochemical stress like diabetes. Plasma gelsolin has been identified earlier to significantly enable injury recovery compared to placebo. This study evaluates the role of rhuGSN for its antioxidant and wound healing properties in murine fibroblasts (3T3-L1 cell line). Total antioxidant capacity of rhuGSN increased in a concentration-dependent manner (0.75-200 μg/mL). Cells pretreated with 0.375 and 0.75 μg/mL rhuGSN for 24 h exhibited a significant increase in viability in a MTT assay. Preincubation of cells with rhuGSN for 24 h followed by oxidative stress induced by exposure to H2O2 for 3 h showed cytoprotective effect. rhuGSN at 12.5 and 25 μg/mL concentration showed an enhanced cell migration after 20 h of injury in a scratch wound healing assay. The proinflammatory cytokine IL-6 levels were elevated in the culture supernatant. These results establish an effective role of rhuGSN against oxidative stress induced by H2O2 and in wound healing of 3T3-L1 fibroblast cells.

scholarly journals S-Allyl Cysteine Alleviates Hydrogen Peroxide Induced Oxidative Injury and Apoptosis through Upregulation of Akt/Nrf-2/HO-1 Signaling Pathway in HepG2 Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Chitra Basu ◽  
Runa Sur
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Cell Viability Assay

Hydrogen peroxide (H2O2) mediated oxidative stress leading to hepatocyte apoptosis plays a pivotal role in the pathophysiology of several chronic liver diseases. This study demonstrates that S-allyl cysteine (SAC) renders cytoprotective effects on H2O2 induced oxidative damage and apoptosis in HepG2 cells. Cell viability assay showed that SAC protected HepG2 cells from H2O2 induced cytotoxicity. Further, SAC treatment dose dependently inhibited H2O2 induced apoptosis via decreasing the Bax/Bcl-2 ratio, restoring mitochondrial membrane potential (∆Ψm), inhibiting mitochondrial cytochrome c release, and inhibiting proteolytic cleavage of caspase-3. SAC protected cells from H2O2 induced oxidative damage by inhibiting reactive oxygen species accumulation and lipid peroxidation. The mechanism underlying the antiapoptotic and antioxidative role of SAC is the induction of the heme oxygenase-1 (HO-1) gene in an NF-E2-related factor-2 (Nrf-2) and Akt dependent manner. Specifically SAC was found to induce the phosphorylation of Akt and enhance the nuclear localization of Nrf-2 in cells. Our results were further confirmed by specific HO-1 gene knockdown studies which clearly demonstrated that HO-1 induction indeed played a key role in SAC mediated inhibition of apoptosis and ROS production in HepG2 cells, thus suggesting a hepatoprotective role of SAC in combating oxidative stress mediated liver diseases.

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