The antioxidant Rutin counteracts the pathological impact of α-synuclein on the enteric nervous system in vitro

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Anne Christmann ◽  
Manuela Gries ◽  
Patrik Scholz ◽  
Pascal L. Stahr ◽  
Jessica Ka Yan Law ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Dopaminergic Neurons ◽  
Synaptic Vesicles ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neuroprotective Effects ◽  
The Brain ◽  
And Oxidative Stress

Abstract Motoric disturbances in Parkinson’s disease (PD) derive from the loss of dopaminergic neurons in the substantia nigra. Intestinal dysfunctions often appear long before manifestation of neuronal symptoms, suggesting a strong correlation between gut and brain in PD. Oxidative stress is a key player in neurodegeneration causing neuronal cell death. Using natural antioxidative flavonoids like Rutin, might provide intervening strategies to improve PD pathogenesis. To explore the potential effects of micro (mRutin) compared to nano Rutin (nRutin) upon the brain and the gut during PD, its neuroprotective effects were assessed using an in vitro PD model. Our results demonstrated that Rutin inhibited the neurotoxicity induced by A53T α-synuclein (Syn) administration by decreasing oxidized lipids and increasing cell viability in both, mesencephalic and enteric cells. For enteric cells, neurite outgrowth, number of synaptic vesicles, and tyrosine hydroxylase positive cells were significantly reduced when treated with Syn. This could be reversed by the addition of Rutin. nRutin revealed a more pronounced result in all experiments. In conclusion, our study shows that Rutin, especially the nanocrystals, are promising natural compounds to protect neurons from cell death and oxidative stress during PD. Early intake of Rutin may provide a realizable option to prevent or slow PD pathogenesis.

scholarly journals Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1702
Author(s):  
Sereen Sandouka ◽  
Tawfeeq Shekh-Ahmad
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Status Epilepticus ◽  
Temporal Lobe Epilepsy ◽  
Antioxidant Capacity ◽  
Temporal Lobe ◽  
Epileptiform Activity ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
The Brain

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.

Apple Phenolics Protect in Vitro Oxidative Stress-induced Neuronal Cell Death

2006 ◽  
Vol 69 (9) ◽  
pp. S357-S360 ◽  
Author(s):  
H. J. Heo ◽  
D.O. Kim ◽  
S.J. Choi ◽  
D.H. Shin ◽  
C.Y. Lee
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals Xenon Neurotoxicity in Rat Hippocampal Slice Cultures Is Similar to Isoflurane and Sevoflurane

2013 ◽  
Vol 119 (2) ◽  
pp. 335-344 ◽  
Author(s):  
Heather Brosnan ◽  
Philip E. Bickler
Keyword(s):  
Cell Death ◽  
Hippocampal Neurons ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neuron Death ◽  
Neuroprotective Effects ◽  
Low Concentrations ◽  
Vitro Model ◽  
Developing Neurons

Abstract Background: Anesthetic neurotoxicity in the developing brain of rodents and primates has raised concern. Xenon may be a nonneurotoxic alternative to halogenated anesthetics, but its toxicity has only been studied at low concentrations, where neuroprotective effects predominate in animal models. An equipotent comparison of xenon and halogenated anesthetics with respect to neurotoxicity in developing neurons has not been made. Methods: Organotypic hippocampal cultures from 7-day-old rats were exposed to 0.75, 1, and 2 minimum alveolar concentrations (MAC) partial pressures (60% xenon at 1.2, 2.67, and 3.67 atm; isoflurane at 1.4, 1.9, and 3.8%; and sevoflurane at 3.4 and 6.8%) for 6 h, at atmospheric pressure or in a pressure chamber. Cell death was assessed 24 h later with fluorojade and fluorescent dye exclusion techniques. Results: Xenon caused death of hippocampal neurons in CA1, CA3, and dentate regions after 1 and 2 MAC exposures, but not at 0.75 MAC. At 1 MAC, xenon increased cell death 40% above baseline (P < 0.01; ANOVA with Dunnett test). Both isoflurane and sevoflurane increased neuron death at 1 but not 2 MAC. At 1 MAC, the increase in cell death compared with controls was 63% with isoflurane and 90% with sevoflurane (both P < 0.001). Pretreatment of cultures with isoflurane (0.75 MAC) reduced neuron death after 1 MAC xenon, isoflurane, and sevoflurane. Conclusion: Xenon causes neuronal cell death in an in vitro model of the developing rodent brain at 1 MAC, as does isoflurane and sevoflurane at similarly potent concentrations. Preconditioning with a subtoxic dose of isoflurane eliminates this toxicity.

scholarly journals Damage to the Endoplasmic Reticulum and Activation of Apoptotic Machinery by Oxidative Stress in Ischemic Neurons

2005 ◽  
Vol 25 (1) ◽  
pp. 41-53 ◽  
Author(s):  
Takeshi Hayashi ◽  
Atsushi Saito ◽  
Shuzo Okuno ◽  
Michel Ferrand-Drake ◽  
Robert L Dodd ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Neuronal Degeneration ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Wild Type ◽  
Transgenic Rats ◽  
The Brain

The endoplasmic reticulum (ER), which plays a role in apoptosis, is susceptible to oxidative stress. Because superoxide is produced in the brain after ischemia/reperfusion, oxidative injury to this organelle may be implicated in ischemic neuronal cell death. Activating transcription factor-4 (ATF-4) and C/EBP-homologous protein (CHOP), both of which are involved in apoptosis, are induced by severe ER stress. Using wild-type and human copper/zinc superoxide dismutase transgenic rats, we observed induction of these molecules in the brain after global cerebral ischemia and compared them with neuronal degeneration. In ischemic, wild-type brains, expression of ATF-4 and CHOP was increased in the hippocampal CA1 neurons that would later undergo apoptosis. Transgenic rats had a mild increase in ATF-4 and CHOP and minimal neuronal degeneration, indicating that superoxide was involved in ER stress-induced cell death. We further confirmed attenuation on induction of these molecules in transgenic mouse brains after focal ischemia. When superoxide was visualized with ethidium, signals for ATF-4 and superoxide overlapped in the same cells. Moreover, lipids in the ER were robustly peroxidized by ischemia but were attenuated in transgenic animals. This indicates that superoxide attacked and damaged the ER, and that oxidative ER damage is implicated in ischemic neuronal cell death.

scholarly journals p21 inhibitor UC2288 ameliorates MPTP induced Parkinson’s disease progression through inhibition of oxidative stress and neuroinflammation

2020 ◽  
Author(s):  
Jun Hyung Im ◽  
In Jun Yeo ◽  
Seong Hee Jeon ◽  
Dong Hun Lee ◽  
Hyeon Joo Ham ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neurodegenerative Disease ◽  
Dopaminergic Neurons ◽  
Kinase Inhibitor ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cultured Neurons ◽  
Dopamine Depletion ◽  
Erk Kinase

Abstract BackgroundParkinson's disease (PD) is a neurodegenerative disease characterized by the early prominent death of dopaminergic neurons and a decrease of dopamine levels. Dopamine depletion leads to several motor dysfunctions, including resting tremor, muscular rigidity, bradykinesia and postural instability. Our previous study determined that knockout of parkin, a gene of PD degrade p21, suppresses neurogenesis which is critical for a neurodegenerative disease. MethodsThus, we investigated the effect of UC2288, an inhibitor of p21, for its therapeutic effect on PD. We found that UC2288 attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral impairment in Rota-rod and Pole test as well as dopamine depletion.ResultsMoreover, UC2288 recovered the number of TH positive cells, but decreased the number of GFAP and Iba-1 positive cells accompanied the decrease of BAX and cleaved caspase3 as well as iNOS and COX-2 expression. In cultured neurons, UC2288 recovered MPP+-induced neuronal cell death in a concentration dependent manner. We also found that UC2288 decreased the p21 reactive cell number, oxidative neuronal damages, cytokines product in vivo and cultured neurons. In a mechanism study, we found that UC2288 significantly decreased the activation of ERK and p38 kinase pathway in the mitogen-activated protein kinase (MAPK) pathway. In addition, 1-10 μM concentration of ERK kinase inhibitor U0126 recovered MPP+-induced neuronal cell death. However, ERK kinase inhibitor U0126 further decreased cell viability with the increase of H2O2.ConclusionThese results indicated that the administration of UC2288 exerted neuroprotective effects on the death of dopaminergic neurons through the suppression of oxidative stress and neuroinflammation via ERK pathway inhibition.

scholarly journals Pomalidomide Ameliorates H2O2-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects

2018 ◽  
Vol 19 (10) ◽  
pp. 3252 ◽  
Author(s):  
Yan-Rou Tsai ◽  
Cheng-Fu Chang ◽  
Jing-Huei Lai ◽  
John Wu ◽  
Yen-Hua Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Mitochondrial Activity ◽  
Neuronal Cultures ◽  
Nuclear Factor ◽  
Neuroprotective Effects ◽  
Stress Injury ◽  
Anti Inflammatory

Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative stress plays a central role in a common pathophysiology that underpins neuronal cell death in acute neurological disorders epitomized by stroke and chronic ones such as Alzheimer’s disease. After cerebral ischemia, for example, inflammation bears a key responsibility in the development of permanent neurological damage. ROS are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Using H2O2-treated rat primary cortical neuronal cultures, we found POM displayed neuroprotective effects against oxidative stress and cell death that associated with changes in the nuclear factor erythroid derived 2/superoxide dismutase 2/catalase signaling pathway. POM also suppressed nuclear factor kappa-light-chain-enhancer (NF-κB) levels and significantly mitigated cortical neuronal apoptosis by regulating Bax, Cytochrome c and Poly (ADP-ribose) polymerase. In summary, POM exerted neuroprotective effects via its anti-oxidative and anti-inflammatory actions against H2O2-induced injury. POM consequently represents a potential therapeutic agent against brain damage and related disorders and warrants further evaluation.

scholarly journals An Insight of Vitamin E as Neuroprotective Agents

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Hui-Min Yap ◽  
Kwan-Liang Lye
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Vitamin E ◽  
Neuronal Cell Death ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Neuronal Cell ◽  
Redox Balance ◽  
The Body ◽  
Neuroprotective Effects

Nervous system is the network of nerve cells that transmits nerve impulses throughout the body. It is rich in both unsaturated fats and irons, making it predominantly susceptible to oxidative stress and damage. Oxidative stress reflects the disruption of the redox balance between the formation and clearance of highly free radicals, for instance reactive oxygen species (ROS) and reactive nitrogen species (RNS). Oxidative stress will further damage the cell lipid, protein and DNA. Oxidative stress has a role in the modulation of critical cellular functions, such as apoptosis program activation, ion transport and calcium mobilization which lead to cell death. Many studies were conducted to prevent neuronal cell death caused by oxidative stress through administration of free radical scavenging antioxidant, such as vitamin E. Vitamin E is known as a chain-breaking antioxidant that showed the capability to increase the viability of neuronal cells that had undergone glutamate injury by inhibiting glutamate-induced pp60 (c-Src) kinase activation. Vitamin E occurs in 8 forms, namely ?-, ?-, ?- and ?-tocopherols and ?-, ?-, ?-and ?-tocotrienols. Tocotrienols differ from tocopherols by possessing an unsaturated isoprenoid side chain instead of a saturated phytyl tail. Tocotrienols, compared to tocopherols, are lightly studied due to the abundance of ?-tocopherol in the human body and its antioxidant properties. Nevertheless, recent studies showed that ?-tocotrienol is more effective in preventing lipid peroxidation compared to ?-tocopherol. Furthermore, tocotrienol was discovered to protect neuronal cell through antioxidant-independent activities. The tocotrienol-rich fraction (TRF) is an extract that consists of 75% tocotrienol and 25% ?-tocopherol. TRF was reported to possess potent antioxidant, anti-inflammation, anticancer and cholesterol-lowering properties. Thus, this writing highlights the significant neuroprotective effects of tocotrienol and tocopherol.

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