PDGF Suppresses Oxidative Stress Induced Ca2+Overload and Calpain Activation in Neurons

Oxidative stress is crucially involved in the pathogenesis of neurological diseases such as stroke and degenerative diseases. We previously demonstrated that platelet-derived growth factors (PDGFs) protected neurons from H2O2-induced oxidative stress and indicated the involvement of PI3K-Akt and MAP kinases as an underlying mechanism. Ca2+overload has been shown to mediate the neurotoxic effects of oxidative stress and excitotoxicity. We examined the effects of PDGFs on H2O2-induced Ca2+overload in primary cultured neurons to further clarify their neuroprotective mechanism. H2O2-induced Ca2+overload in neurons in a dose-dependent manner, while pretreating neurons with PDGF-BB for 24 hours largely suppressed it. In a comparative study, the suppressive effects of PDGF-BB were more potent than those of PDGF-AA. We then evaluated calpain activation, which was induced by Ca2+overload and mediated both apoptotic and nonapoptotic cell death. H2O2-induced calpain activation in neurons in a dose-dependent manner. Pretreatment of PDGF-BB completely blocked H2O2-induced calpain activation. To the best of our knowledge, the present study is the first to demonstrate the mechanism underlying the neuroprotective effects of PDGF against oxidative stress via the suppression of Ca2+overload and inactivation of calpain and suggests that PDGF-BB may be a potential therapeutic target of neurological diseases.

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Apamin Enhances Neurite Outgrowth and Regeneration after Laceration Injury in Cortical Neurons

Toxins ◽

10.3390/toxins13090603 ◽

2021 ◽

Vol 13 (9) ◽

pp. 603

Author(s):

Hyunseong Kim ◽

Jin Young Hong ◽

Junseon Lee ◽

Wan-Jin Jeon ◽

In-Hyuk Ha

Keyword(s):

Phospholipase A2 ◽

Neurite Outgrowth ◽

Cortical Neurons ◽

Neurological Diseases ◽

Minor Component ◽

Underlying Mechanism ◽

Bee Venom ◽

Dependent Manner ◽

Neuroprotective Effects ◽

Wide Range

Apamin is a minor component of bee venom and is a polypeptide with 18 amino acid residues. Although apamin is considered a neurotoxic compound that blocks the potassium channel, its neuroprotective effects on neurons have been recently reported. However, there is little information about the underlying mechanism and very little is known regarding the toxicological characterization of other compounds in bee venom. Here, cultured mature cortical neurons were treated with bee venom components, including apamin, phospholipase A2, and the main component, melittin. Melittin and phospholipase A2 from bee venom caused a neurotoxic effect in dose-dependent manner, but apamin did not induce neurotoxicity in mature cortical neurons in doses of up to 10 µg/mL. Next, 1 and 10 µg/mL of apamin were applied to cultivate mature cortical neurons. Apamin accelerated neurite outgrowth and axon regeneration after laceration injury. Furthermore, apamin induced the upregulation of brain-derived neurotrophic factor and neurotrophin nerve growth factor, as well as regeneration-associated gene expression in mature cortical neurons. Due to its neurotherapeutic effects, apamin may be a promising candidate for the treatment of a wide range of neurological diseases.

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Chikusetsu saponin V attenuates H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells through Sirt1/PGC-1α/Mn-SOD signaling pathways

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0262 ◽

2016 ◽

Vol 94 (9) ◽

pp. 919-928 ◽

Cited By ~ 20

Author(s):

Jingzhi Wan ◽

Lili Deng ◽

Changcheng Zhang ◽

Qin Yuan ◽

Jing Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Neurodegenerative Diseases ◽

Signaling Pathways ◽

Vital Role ◽

Dependent Manner ◽

Neuroprotective Effects ◽

Human Neuroblastoma ◽

Ros Accumulation ◽

Antioxidative Effects ◽

Dose Dependent

Oxidative stress plays a vital role in the pathogenesis of neurodegenerative diseases. Chikusetsu saponin V (CsV), the most abundant member of saponins from Panax japonicus (SPJ), has attracted increasing attention for its potential to treat neurodegenerative diseases. However, the mechanisms are unclear. Our study intended to investigate the antioxidative effects of CsV in human neuroblastoma SH-SY5Y cells. Our data showed that CsV attenuated H2O2-induced cytotoxicity, inhibited ROS accumulation, increased the activities of superoxide dismutase (SOD) and GSH, and increased mitochondrial membrane potential dose-dependently. Further exploration of the mechanisms showed that CsV exhibited these effects through increasing the activation of oxidative-stress-associated factors including Sirt1, PGC-1α, and Mn-SOD. Moreover, CsV inhibited H2O2-induced down-regulation of Bcl-2 and up-regulation of Bax in a dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. In conclusion, our study demonstrated that CsV exhibited neuroprotective effects possibly through Sirt1/PGC-1α/Mn-SOD signaling pathways.

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Ganoderma lucidumProtects Dopaminergic Neuron Degeneration through Inhibition of Microglial Activation

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nep075 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 16

Author(s):

Ruiping Zhang ◽

Shengli Xu ◽

Yanning Cai ◽

Ming Zhou ◽

Xiaohong Zuo ◽

...

Keyword(s):

Microglial Activation ◽

Neuroprotective Effect ◽

Mrna Level ◽

Underlying Mechanism ◽

Dependent Manner ◽

Chinese Medicinal Herb ◽

Neuroprotective Effects ◽

Promising Therapeutic Target ◽

Progressive Neurodegeneration ◽

Dose Dependent

Abundant evidence has suggested that neuroinflammation participates in the pathogenesis of Parkinson's disease (PD). The emerging evidence has supported that microglia may play key roles in the progressive neurodegeneration in PD and might be a promising therapeutic target.Ganoderma lucidum(GL), a traditional Chinese medicinal herb, has been shown potential neuroprotective effects in our clinical trials that make us to speculate that it might possess potent anti-inflammatory and immunomodulating properties. To test this hypothesis, we investigated the potential neuroprotective effect of GL and possible underlying mechanism of action through protecting microglial activation using co-cultures of dopaminergic neurons and microglia. The microglia is activated by LPS and MPP+-treated MES 23.5 cell membranes. Meanwhile, GL extracts significantly prevent the production of microglia-derived proinflammatory and cytotoxic factors [nitric oxide, tumor necrosis factor-α(TNF-α), interlukin 1β(IL-1β)] in a dose-dependent manner and down-regulate the TNF-αand IL-1βexpressions on mRNA level as well. In conclusion, our results support that GL may be a promising agent for the treatment of PD through anti-inflammation.

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Behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy: Possible mechanisms of neurotoxic effects

Archives of Biological Sciences ◽

10.2298/abs1203829m ◽

2012 ◽

Vol 64 (3) ◽

pp. 829-841 ◽

Cited By ~ 1

Author(s):

D. Mladenovic ◽

D. Hrncic ◽

A. Rasic-Markovic ◽

Olivera Stanojlovic

Keyword(s):

Oxidative Stress ◽

Hepatic Encephalopathy ◽

Liver Failure ◽

Experimental Model ◽

Alpha Power ◽

Dependent Manner ◽

Chronic Liver Failure ◽

Toxic Metabolites ◽

Neurotoxic Effects ◽

Dose Dependent

Although there is still no ideal experimental model of hepatic encephalopathy, thioacetamide is widely used for the induction of acute and chronic liver failure. Thioacetamide exerts hepatotoxic effects through the formation of toxic metabolites in hepatocytes, oxidative stress and calcium mobilization. An ideal experimental model of hepatic encephalopathy should have similar behavioral and electroencephalographic manifestations as human encephalopathy. Thioacetamide induces motor manifestations in a dose-dependent manner. Milder forms of thioacetamide-induced encephalopathy are associated with an increase in relative alpha power, while more severe forms are followed by a flattening of the electroencephalogram. liver failure-induced hyperammonemia has a pivotal role in the neurotoxic effects of thioacetamide. Hyperammonemia induces brain edema, alterations in neurotransmission, oxidative stress, mitochondrial dysfunction and neuronal death. The aim of this article is to review the behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy, as well as to summarize potential mechanisms involved in thioacetamide neurotoxicity.

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Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

International Journal of Molecular Sciences ◽

10.3390/ijms22094717 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4717

Author(s):

Jin-Young Lee ◽

Da-Ae Kim ◽

Eun-Young Kim ◽

Eun-Ju Chang ◽

So-Jeong Park ◽

...

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Map Kinases ◽

Osteoclast Differentiation ◽

Dependent Manner ◽

Dual Action ◽

Dose Dependent ◽

Resorptive Activity

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

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Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats

Cellular Physiology and Biochemistry ◽

10.1159/000481876 ◽

2017 ◽

Vol 43 (4) ◽

pp. 1449-1459 ◽

Cited By ~ 4

Author(s):

Renata A. C. Silva ◽

Andréa F. Gonçalves ◽

Priscila P. dos Santos ◽

Bruna Rafacho ◽

Renan F. T. Claro ◽

...

Keyword(s):

Oxidative Stress ◽

Retinoic Acid ◽

Energy Metabolism ◽

Cardiac Remodeling ◽

Citrate Synthase ◽

Isolated Heart ◽

Lipid Hydroperoxide ◽

Dependent Manner ◽

Heart Study ◽

Dose Dependent

Background/Aims: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. Methods and Results: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-β, PI3K, AKT, NFκB, S6K, and ERK. Conclusion: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.

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Preclinical Study on the Ameliorating Effect of L-Ascorbic Acid for the Oxidative Stress of Caused by Chronic Administration of Organic Nitrates in Cardiovascular Diseases

10.21203/rs.3.rs-968191/v1 ◽

2021 ◽

Author(s):

Ahmed M Hamdan ◽

Zuhair M. Mohammedsaleh ◽

Aalaa Aboelnour ◽

Sherif M.H. Elkhannishi

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Ascorbic Acid ◽

Chronic Administration ◽

Stress Factors ◽

Male Rats ◽

Oxidative Stress Marker ◽

Organic Nitrates ◽

Dependent Manner ◽

Dose Dependent

Abstract PurposeThe therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. The principal objective of our research is to explain the ameliorating effect of L-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs. MethodsWe studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered ISMN. Afterwards, we evaluated the role of L-ascorbic acid against these biochemical changes. ResultsChronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in myocardium muscles in a dose dependent manner. Meanwhile, such exposure caused decline in the enzymatic effect of superoxide dismutase (SOD), glutathione (GSH) and catalase activity (CAT) accompanied with a decrease of in the level of mitochondrial oxidative stress marker (nrf2) in myocardium muscles and decrease in the serum iron and total iron binding capacity (TIBC) in a dose dependent manner. Concomitant treatment with L-ascorbic acid significantly diminished these changes for all examined parameters.ConclusionChronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to generation of reactive oxygen species. Using vitamin C can effectively ameliorate such intoxication to overcome the nitrate tolerance.

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Oxidative stress biomarkers in the gills of the bivalve Mactra stultorum exposed to acrylamide

Scientia Marina ◽

10.3989/scimar.04993.11a ◽

2020 ◽

Vol 84 (2) ◽

Author(s):

Wafa Trabelsi ◽

Chaima Fouzai ◽

Imene Chetoui ◽

Safa Bejaoui ◽

Khaoula Telahigue ◽

...

Keyword(s):

Oxidative Stress ◽

Ache Activity ◽

Reduced Glutathione ◽

Lipid Hydroperoxides ◽

Dependent Manner ◽

Advanced Oxidation Protein Products ◽

Oxidative Stress Biomarkers ◽

Stress Biomarkers ◽

The Subject ◽

Dose Dependent

Acrylamide (ACR) is among the most deleterious pollutants in the environment and presents a serious risk to humans and ecosystems. The purpose of this study was to assess its effects when administered at different concentrations (5, 10 and 20 mg L–1) to evaluate antioxidant status in the gills of Mactra stultorum. Our results showed, after five days of treatment, an increase in malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), reduced glutathione (GSH), ascorbic acid (Vit C) and metallothionein (MDA) levels in gills of treated clams compared with controls. Moreover, an increase in superoxide dismutase (SOD) and a significant decrease in glutathione peroxidase (GPx) activities were also observed. Acrylamide induced neurotoxicity, as evidenced by the inhibition of acetylcholinesterase (AChE) activity in a dose-dependent manner. Overall, our results indicated that oxidative stress may be considered one of the mechanisms behind acrylamide toxicity in bivalves, although the subject requires more research.

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Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the Akt/GSK-3β/Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 5/6 Nephrectomized Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/2853534 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 7

Author(s):

Hong-feng Zhang ◽

Jia-hong Wang ◽

Yan-li Wang ◽

Cheng Gao ◽

Yan-ting Gu ◽

...

Keyword(s):

Oxidative Stress ◽

Western Blot ◽

Signaling Pathway ◽

Kidney Injury ◽

Dependent Manner ◽

Salvianolic Acid ◽

Nrf2 Signaling Pathway ◽

Antioxidative Effects ◽

Dose Dependent

Salvianolic acid A (SAA) is a bioactive polyphenol extracted from Salviae miltiorrhizae Bunge, which possesses a variety of pharmacological activities. In our previous study, we have demonstrated that SAA effectively attenuates kidney injury and inflammation in an established animal model of 5/6 nephrectomized (5/6Nx) rats. However, there has been limited research regarding the antioxidative effects of SAA on chronic kidney disease (CKD). Here, we examined the antioxidative effects and underlying mechanisms of SAA in 5/6Nx rats. The rats were injected with SAA (2.5, 5, and 10 mg·kg-1·d-1, ip) for 28 days. Biochemical, flow cytometry, and Western blot analyses showed that SAA significantly increased the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GPx), and catalase (CAT) and lowered the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and NADPH oxidase 4 (NOX-4) in a dose-dependent manner in 5/6Nx rats and in H2O2-induced HK-2 cells in vitro. Moreover, SAA enhanced the activation of the protein kinase B/glycogen synthase kinase-3β/nuclear factor-erythroid-2-related factor 2 (Akt/GSK-3β/Nrf2) signaling pathway in a dose-dependent manner and subsequently increased the expression of heme oxygenase-1 (HO-1) in the kidney of 5/6Nx rats, which were consistent with those obtained in H2O2-induced HK-2 cells in vitro shown by Western blot analysis. Furthermore, SAA significantly increased the expression of intranuclear Nrf2 and HO-1 proteins compared to HK-2 cells stimulated by LPS on the one hand, which can be enhanced by QNZ to some extent; on the other hand, SAA significantly lowered the expression of p-NF-κB p65 and ICAM-1 proteins compared to HK-2 cells stimulated by H2O2, which can be abrogated by ML385 to some extent. In conclusion, our results demonstrated that SAA effectively protects the kidney against oxidative stress in 5/6Nx rats. One of the pivotal mechanisms for the protective effects of SAA on kidney injury was mainly related with its antioxidative roles by activating the Akt/GSK-3β/Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway.

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Antioxidant activity of different extracts of Argentinian medicinal plants against arsenic-induced toxicity in renal cells

Human & Experimental Toxicology ◽

10.1177/0960327108092192 ◽

2008 ◽

Vol 27 (4) ◽

pp. 341-346 ◽

Cited By ~ 12

Author(s):

EA Soria ◽

ME Goleniowski ◽

JJ Cantero ◽

GA Bongiovanni

Keyword(s):

Oxidative Stress ◽

Antioxidant Activity ◽

Medicinal Plants ◽

Arsenic Exposure ◽

Vero Cells ◽

Lipid Hydroperoxides ◽

Dependent Manner ◽

Renal Cells ◽

Popular Medicine ◽

Dose Dependent

Chronic toxicity of arsenic resulting from drinking water is a health problem encountered in humans, especially in South America and Asia, where a correlation between oxidative stress, tumor promotion, and arsenic exposure has been observed. Differential solvent extraction (petroleum ether (PE); dichloromethane (DCM); methanol (OL) and water (W)) was performed to compare the protective (antioxidant) activity of five Argentinian medicinal plants on arsenite-induced oxidative stress in Vero cells, assayed by hydroperoxide measurement. The results were analyzed using ANOVA followed by the LSD Fisher test. The data showed that arsenite was a pro-oxidant agent which acts in a time–dose-dependent manner. Extracts from Eupatorium buniifolium (PE), Lantana grisebachii (PE, W), Mandevilla pentlandiana (PE, W), and Sebastiania commersoniana (DCM, OL, W) prevented the formation of both aqueous and lipid hydroperoxides, but Heterothalamus alienus only impeded lipid ones. Therefore, antioxidant extracts are potentially beneficial and may have a protective activity against arsenite-induced renal injury. Among these, the aqueous extract of L. grisebachii may represent the most suitable preparation for humans since the traditional usage of this plant in popular medicine is through consumption of tea.

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