scholarly journals Indomethacin Ameliorates Trimethyltin-Induced Neuronal Damage in Vivo by Attenuating Oxidative Stress in the Dentate Gyrus of Mice

2011 ◽  
Vol 34 (12) ◽  
pp. 1856-1863 ◽  
Author(s):  
Nguyen Quynh Huong ◽  
Yukary Nakamura ◽  
Nobuyuki Kuramoto ◽  
Masanori Yoneyama ◽  
Reiko Nagashima ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dentate Gyrus ◽  
Neuronal Damage

In vivo depletion of endogenous glutathione facilitates trimethyltin-induced neuronal damage in the dentate gyrus of mice by enhancing oxidative stress

2008 ◽  
Vol 52 (4-5) ◽  
pp. 761-769 ◽  
Author(s):  
Masanori Yoneyama ◽  
Norito Nishiyama ◽  
Makoto Shuto ◽  
Chie Sugiyama ◽  
Koichi Kawada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dentate Gyrus ◽  
Neuronal Damage

scholarly journals Neuroprotection by Brazilian Green Propolis againstIn vitroandIn vivoIschemic Neuronal Damage

2005 ◽  
Vol 2 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Masamitsu Shimazawa ◽  
Satomi Chikamatsu ◽  
Nobutaka Morimoto ◽  
Satoshi Mishima ◽  
Hiroichi Nagai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Brain Infarction ◽  
Folk Medicine ◽  
Neuroprotective Function ◽  
Brazilian Green Propolis

We examined whether Brazilian green propolis, a widely used folk medicine, has a neuroprotective functionin vitroand/orin vivo.In vitro, propolis significantly inhibited neurotoxicity induced in neuronally differentiated PC12 cell cultures by either 24 h hydrogen peroxide (H2O2) exposure or 48 h serum deprivation. Regarding the possible underlying mechanism, propolis protected against oxidative stress (lipid peroxidation) in mouse forebrain homogenates and scavenged free radicals [induced by diphenyl-p-picrylhydrazyl (DPPH). In micein vivo, propolis [30 or 100 mg/kg; intraperitoneally administered four times (at 2 days, 1 day and 60 min before, and at 4 h after induction of focal cerebral ischemia by permanent middle cerebral artery occlusion)] reduced brain infarction at 24 h after the occlusion. Thus, a propolis-induced inhibition of oxidative stress may be partly responsible for its neuroprotective function againstin vitrocell death andin vivofocal cerebral ischemia.

scholarly journals Inhibition of Oxidative Neurotoxicity and Scopolamine-Induced Memory Impairment by γ-Mangostin: In Vitro and In Vivo Evidence

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Youngmun Lee ◽  
Sunyoung Kim ◽  
Yeonsoo Oh ◽  
Young-Mi Kim ◽  
Young-Won Chin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Memory Impairment ◽  
Neuronal Damage ◽  
Biological Activities ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ros Generation ◽  
Garcinia Mangostana

Among a series of xanthones identified from mangosteen, the fruit of Garcinia mangostana L. (Guttifereae), α- and γ-mangostins are known to be major constituents exhibiting diverse biological activities. However, the effects of γ-mangostin on oxidative neurotoxicity and impaired memory are yet to be elucidated. In the present study, the protective effect of γ-mangostin on oxidative stress-induced neuronal cell death and its underlying action mechanism(s) were investigated and compared to that of α-mangostin using primary cultured rat cortical cells. In addition, the effect of orally administered γ-mangostin on scopolamine-induced memory impairment was evaluated in mice. We found that γ-mangostin exhibited prominent protection against H2O2- or xanthine/xanthine oxidase-induced oxidative neuronal death and inhibited reactive oxygen species (ROS) generation triggered by these oxidative insults. In contrast, α-mangostin had no effects on the oxidative neuronal damage or associated ROS production. We also found that γ-mangostin, not α-mangostin, significantly inhibited H2O2-induced DNA fragmentation and activation of caspases 3 and 9, demonstrating its antiapoptotic action. In addition, only γ-mangostin was found to effectively inhibit lipid peroxidation and DPPH radical formation, while both mangostins inhibited β-secretase activity. Furthermore, we observed that the oral administration of γ-mangostin at dosages of 10 and 30 mg/kg markedly improved scopolamine-induced memory impairment in mice. Collectively, these results provide both in vitro and in vivo evidences for the neuroprotective and memory enhancing effects of γ-mangostin. Multiple mechanisms underlying this neuroprotective action were suggested in this study. Based on our findings, γ-mangostin could serve as a potentially preferable candidate over α-mangostin in combatting oxidative stress-associated neurodegenerative diseases including Alzheimer’s disease.

Abstract P70: SPAK/OSR1 Signaling as a Novel Target for Post-Stroke Oxidative Stress Brain Injury

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Jun Wang ◽  
Victoria M Fiesler ◽  
Gulnaz Begum ◽  
Mohammad Iqbal H Bhuiyan ◽  
Shuying Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Brain Injury ◽  
Neuronal Damage ◽  
Recombinant Tissue Plasminogen Activator ◽  
Primary Therapy ◽  
Post Stroke ◽  
Stroke Models ◽  
Novel Target

Stroke is the second leading cause of death worldwide, and ischemic stroke accounts for the vast majority of stroke cases. Currently, recombinant tissue plasminogen activator and endovascular thrombectomy are the two primary therapy strategies for acute ischemic stroke patients. Reactive oxygen species (ROS)-mediated oxidative stress can cause brain injury during reperfusion. We have shown that the Ste20/SPS1-related proline-alanine-rich protein kinase/oxidative stress-responsive kinase-1 (SPAK/OSR1) are activated in ischemic stroke brains, resulting in worsened outcomes in murine stroke models. SPAK activation induces the production of pro-inflammatory cytokines. Post-stroke administration of a novel SPAK inhibitor ZT-1a attenuates cerebral edema and protects against brain damage in in vivo model of ischemic stroke. However, whether ROS mediated oxidative stress directly activate SPAK/OSR1 pathway and induces SPAK pro-inflammatory cytokine production in ischemic brains remains unknown. In our extended study, we examined activation of SPAK/OSR1 and its substrate Na-K-Cl cotransporter (NKCC1) in cultured mouse primary neurons in response to hydrogen peroxide (H 2 O 2 )-mediated oxidative stress. We found that exposure of neurons to H 2 O 2 for 24 hrs triggered upregulation of protein expression and phosphorylation activation of SPAK/OSR1 and NKCC1 ( p < 0.05), which are accompanied with an increase in intracellular Na + concentration and neuronal death ( p < 0.01). These changes were blocked by an ROS scavenger ebselen. Interestingly, both novel SPAK inhibitor ZT-1a and NKCC1 inhibitor bumetanide are able to block H 2 O 2 -induced neuronal damage. We are in the process to assess effects of SPAK inhibitor ZT-1a in reducing ROS-mediated inflammation and brain injury in in vivo model of ischemic stroke. Together, our study suggests that ROS can activate SPAK/OSR1 complex during reperfusion injury and the therapeutic potentials of SPAK inhibitor ZT-1a for ischemic stroke.

Minocycline inhibits oxidative stress and decreases in vitro and in vivo ischemic neuronal damage

2005 ◽  
Vol 1044 (1) ◽  
pp. 8-15 ◽  
Author(s):  
Nobutaka Morimoto ◽  
Masamitsu Shimazawa ◽  
Tetsumori Yamashima ◽  
Hiroichi Nagai ◽  
Hideaki Hara
Keyword(s):  
Oxidative Stress ◽  
Neuronal Damage

Brain aluminium accumulation and oxidative stress in the presence of calcium silicate dental cements

2016 ◽  
Vol 36 (10) ◽  
pp. 1071-1080 ◽  
Author(s):  
K Demirkaya ◽  
B Can Demirdöğen ◽  
Z Öncel Torun ◽  
O Erdem ◽  
E Çırak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Calcium Silicate ◽  
Neuronal Damage ◽  
Control Group ◽  
Tbars Level ◽  
Extraction Socket ◽  
Dental Cement ◽  
The Brain ◽  
And Oxidative Stress

Mineral trioxide aggregate (MTA) is a calcium silicate dental cement used for various applications in dentistry. This study was undertaken to test whether the presence of three commercial brands of calcium silicate dental cements in the dental extraction socket of rats would affect the brain aluminium (Al) levels and oxidative stress parameters. Right upper incisor was extracted and polyethylene tubes filled with MTA Angelus, MTA Fillapex or Theracal LC, or left empty for the control group, were inserted into the extraction socket. Rats were killed 7, 30 or 60 days after operation. Brain tissues were obtained before killing. Al levels were measured by atomic absorption spectrometry. Thiobarbituric acid reactive substances (TBARS) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined using spectrophotometry. A transient peak was observed in brain Al level of MTA Angelus group on day 7, while MTA Fillapex and Theracal LC groups reached highest brain Al level on day 60. Brain TBARS level, CAT, SOD and GPx activities transiently increased on day 7 and then returned to almost normal levels. This in vivo study for the first time indicated that initial washout may have occurred in MTA Angelus, while element leaching after the setting is complete may have taken place for MTA Fillapex and Theracal LC. Moreover, oxidative stress was induced and antioxidant enzymes were transiently upregulated. Further studies to search for oxidative neuronal damage should be done to completely understand the possible toxic effects of calcium silicate cements on the brain.

scholarly journals METTL3-dependent RNA m6A dysregulation contributes to neurodegeneration in Alzheimer’s disease through aberrant cell cycle events

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Fanpeng Zhao ◽  
Ying Xu ◽  
Shichao Gao ◽  
Lixia Qin ◽  
Quillan Austria ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Neuronal Damage ◽  
Underlying Mechanism ◽  
Aβ Oligomers ◽  
Aberrant Cell ◽  
Soluble Aβ Oligomers ◽  
The Impact

Abstract Background N6-methyladenosine (m6A) modification of RNA influences fundamental aspects of RNA metabolism and m6A dysregulation is implicated in various human diseases. In this study, we explored the potential role of RNA m6A modification in the pathogenesis of Alzheimer disease (AD). Methods We investigated the m6A modification and the expression of m6A regulators in the brain tissues of AD patients and determined the impact and underlying mechanism of manipulated expression of m6A levels on AD-related deficits both in vitro and in vivo. Results We found decreased neuronal m6A levels along with significantly reduced expression of m6A methyltransferase like 3 (METTL3) in AD brains. Interestingly, reduced neuronal m6A modification in the hippocampus caused by METTL3 knockdown led to significant memory deficits, accompanied by extensive synaptic loss and neuronal death along with multiple AD-related cellular alterations including oxidative stress and aberrant cell cycle events in vivo. Inhibition of oxidative stress or cell cycle alleviated shMettl3-induced apoptotic activation and neuronal damage in primary neurons. Restored m6A modification by inhibiting its demethylation in vitro rescued abnormal cell cycle events, neuronal deficits and death induced by METTL3 knockdown. Soluble Aβ oligomers caused reduced METTL3 expression and METTL3 knockdown exacerbated while METTL3 overexpression rescued Aβ-induced synaptic PSD95 loss in vitro. Importantly, METTL3 overexpression rescued Aβ-induced synaptic damage and cognitive impairment in vivo. Conclusions Collectively, these data suggested that METTL3 reduction-mediated m6A dysregulation likely contributes to neurodegeneration in AD which may be a therapeutic target for AD.

Glial cytotoxicity of low doses of cadmium as a model of heavy metal pollution influence on vertebrates

2020 ◽  
Vol 31 (1) ◽  
pp. 3-10
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
A. M. Hahut ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Oxidative Damage ◽  
Cadmium Chloride ◽  
Glioma Cells ◽  
Low Doses ◽  
Genotoxic Effects ◽  
Cadmium Ions

Cadmium is a common transition metal that entails an extremely wide range of toxic effects in humans and animals. The cytotoxicity of cadmium ions and its compounds is due to various genotoxic effects, including both DNA damage and chromosomal aberrations. Some bone diseases, kidney and digestive system diseases are determined as pathologies that are closely associated with cadmium intoxication. In addition, cadmium is included in the list of carcinogens because of its ability to initiate the development of tumors of several forms of cancer under conditions of chronic or acute intoxication. Despite many studies of the effects of cadmium in animal models and cohorts of patients, in which cadmium effects has occurred, its molecular mechanisms of action are not fully understood. The genotoxic effects of cadmium and the induction of programmed cell death have attracted the attention of researchers in the last decade. In recent years, the results obtained for in vivo and in vitro experimental models have shown extremely high cytotoxicity of sublethal concentrations of cadmium and its compounds in various tissues. One of the most studied causes of cadmium cytotoxicity is the development of oxidative stress and associated oxidative damage to macromolecules of lipids, proteins and nucleic acids. Brain cells are most sensitive to oxidative damage and can be a critical target of cadmium cytotoxicity. Thus, oxidative damage caused by cadmium can initiate genotoxicity, programmed cell death and inhibit their viability in the human and animal brains. To test our hypothesis, cadmium cytotoxicity was assessed in vivo in U251 glioma cells through viability determinants and markers of oxidative stress and apoptosis. The result of the cell viability analysis showed the dose-dependent action of cadmium chloride in glioma cells, as well as the generation of oxidative stress (p <0.05). Calculated for 48 hours of exposure, the LD50 was 3.1 μg×ml-1. The rates of apoptotic death of glioma cells also progressively increased depending on the dose of cadmium ions. A high correlation between cadmium concentration and apoptotic response (p <0.01) was found for cells exposed to 3–4 μg×ml-1 cadmium chloride. Moreover, a significant correlation was found between oxidative stress (lipid peroxidation) and induction of apoptosis. The results indicate a strong relationship between the generation of oxidative damage by macromolecules and the initiation of programmed cell death in glial cells under conditions of low doses of cadmium chloride. The presented results show that cadmium ions can induce oxidative damage in brain cells and inhibit their viability through the induction of programmed death. Such effects of cadmium intoxication can be considered as a model of the impact of heavy metal pollution on vertebrates.

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