Deficiency in Neuroserpin Exacerbates CoCl2 Induced Hypoxic Injury in the Zebrafish Model by Increased Oxidative Stress

Protective strategy against hypoxic-ischemic (H/I) induced injury has been intensively discussed. Neuroserpin, an inhibitor for tissue plasminogen activator (tPA), has been proved a vital neuroprotective agent in cerebral ischemia mouse model and oxygen-glucose deprivation and reoxygenation (OGD/R) cell model. Neuroserpin is a promising therapeutic hint for neonatal hypoxic-ischemia injury. Here, we established a neuroserpin deficient zebrafish to study its role in CoCl2 chemically induced hypoxic injury. CoCl2 exposure was beginning at the embryonic stage. Development defects, neuronal loss, and vascular malformation was assessed by imaging microscopy. Neuroserpin deficient zebrafish showed more development defects, neuronal loss and vascular malformation compared to wide-type. Apoptosis and oxidative stress were evaluated to further identify the possible mechanisms. These findings indicate that neuroserpin could protective against CoCl2 induced hypoxic injury by alleviating oxidative stress.

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Protective Effect of Triphala against Oxidative Stress-Induced Neurotoxicity

BioMed Research International ◽

10.1155/2021/6674988 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Wanchen Ning ◽

Simin Li ◽

Jokyab Tsering ◽

Yihong Ma ◽

Honghong Li ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Activities ◽

Cell Model ◽

Neuroprotective Effect ◽

Flow Cytometric Analysis ◽

Mitogen Activated Protein Kinase ◽

Protective Effects ◽

Zebrafish Model

Background. Oxidative stress is implicated in the progression of many neurological diseases, which could be induced by various chemicals, such as hydrogen peroxide (H2O2) and acrylamide. Triphala is a well-recognized Ayurvedic medicine that possesses different therapeutic properties (e.g., antihistamine, antioxidant, anticancer, anti-inflammatory, antibacterial, and anticariogenic effects). However, little information is available regarding the neuroprotective effect of Triphala on oxidative stress. Materials and Methods. An in vitro H2O2-induced SH-SY5Y cell model and an in vivo acrylamide-induced zebrafish model were established. Cell viability, apoptosis, and proliferation were examined by MTT assay, ELISA, and flow cytometric analysis, respectively. The molecular mechanism underlying the antioxidant activity of Triphala against H2O2 was investigated dose dependently by Western blotting. The in vivo neuroprotective effect of Triphala on acrylamide-induced oxidative injury in Danio rerio was determined using immunofluorescence staining. Results. The results indicated that Triphala plays a neuroprotective role against H2O2 toxicity in inhibiting cell apoptosis and promoting cell proliferation. Furthermore, Triphala pretreatment suppressed the phosphorylation of the mitogen-activated protein kinase (MARK) signal pathway (p-Erk1/2, p-JNK1/2, and p-p38), whereas it restored the activities of antioxidant enzymes (superoxide dismutase 1 (SOD1) and catalase) in the H2O2-treated SH-SY5Y cells. Consistently, similar protective effects of Triphala were observed in declining neuroapoptosis and scavenging free radicals in the zebrafish central neural system, possessing a critical neuroprotective property against acrylamide-induced oxidative stress. Conclusion. In summary, Triphala is a promising neuroprotective agent against oxidative stress in SH-SY5Y cells and zebrafishes with significant antiapoptosis and antioxidant activities.

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MiR-485-5p Promotes Neuron Survival through Mediating Rac1/Notch2 Signaling Pathway after Cerebral Ischemia/Reperfusion

Current Neurovascular Research ◽

10.2174/1567202617666200415154822 ◽

2020 ◽

Vol 17 (3) ◽

pp. 259-266 ◽

Cited By ~ 2

Author(s):

Xuan Chen ◽

Sumei Zhang ◽

Peipei Shi ◽

Yangli Su ◽

Dong Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Therapeutic Option ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Small Gtpase ◽

Luciferase Reporter ◽

Pathological Feature ◽

In Cells

Objective: Ischemia-reperfusion (I/R) injury is a pathological feature of ischemic stroke. This study investigated the regulatory role of miR-485-5p in I/R injury. Methods: SH-SY5Y cells were induced with oxygen and glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Cells were transfected with designated constructs (miR-485- 5p mimics, miR-485-5p inhibitor, lentiviral vectors overexpressing Rac1 or their corresponding controls). Cell viability was evaluated using the MTT assay. The concentrations of lactate dehydrogenase, malondialdehyde, and reactive oxygen species were detected to indicate the degree of oxidative stress. Flow cytometry and caspase-3 activity assay were used for apoptosis assessment. Dual-luciferase reporter assay was performed to confirm that Rac family small GTPase 1 (Rac1) was a downstream gene of miR-485-5p. Results: OGD/R resulted in decreased cell viability, elevated oxidative stress, increased apoptosis, and downregulated miR-485-5p expression in SH-SY5Y cells. MiR-485-5p upregulation alleviated I/R injury, evidenced by improved cell viability, decreased oxidative markers, and reduced apoptotic rate. OGD/R increased the levels of Rac1 and neurogenic locus notch homolog protein 2 (Notch2) signaling-related proteins in cells with normal miR-485-5p expression, whereas miR- 485-5p overexpression successfully suppressed OGD/R-induced upregulation of these proteins. Furthermore, the delivery of vectors overexpressing Rac1 in miR-485-5p mimics-transfected cells reversed the protective effect of miR-485-5p in cells with OGD/R-induced injury. Conclusion: This study showed that miR-485-5p protected cells following I/R injury via targeting Rac1/Notch2 signaling suggest that targeted upregulation of miR-485-5p might be a promising therapeutic option for the protection against I/R injury.

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Calycosin-7-O-β-D-glucoside Attenuates OGD/R-Induced Damage by Preventing Oxidative Stress and Neuronal Apoptosis via the SIRT1/FOXO1/PGC-1α Pathway in HT22 Cells

Neural Plasticity ◽

10.1155/2019/8798069 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Xiangli Yan ◽

Aiming Yu ◽

Haozhen Zheng ◽

Shengxin Wang ◽

Yingying He ◽

...

Keyword(s):

Oxidative Stress ◽

Neuronal Apoptosis ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Pathological Process ◽

Neuroprotective Effects ◽

Ht22 Cells ◽

Positive Effects ◽

Antioxidant Stress

Neuronal apoptosis induced by oxidative stress is a major pathological process that occurs after cerebral ischemia-reperfusion. Calycosin-7-O-β-D-glucoside (CG) is a representative component of isoflavones in Radix Astragali (RA). Previous studies have shown that CG has potential neuroprotective effects. However, whether CG alleviates neuronal apoptosis through antioxidant stress after ischemia-reperfusion remains unknown. To investigate the positive effects of CG on oxidative stress and apoptosis of neurons, we simulated the ischemia-reperfusion process in vitro using an immortalized hippocampal neuron cell line (HT22) and oxygen-glucose deprivation/reperfusion (OGD/R) model. CG significantly improved cell viability and reduced oxidative stress and neuronal apoptosis. In addition, CG treatment upregulated the expression of SIRT1, FOXO1, PGC-1α, and Bcl-2 and downregulated the expression of Bax. In summary, our findings indicate that CG alleviates OGD/R-induced damage via the SIRT1/FOXO1/PGC-1α signaling pathway. Thus, CG maybe a promising therapeutic candidate for brain injury associated with ischemic stroke.

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Nrf2 mediates the neuroprotective effect of isoflurane preconditioning in cortical neuron injury induced by oxygen-glucose deprivation

Human & Experimental Toxicology ◽

10.1177/0960327121989416 ◽

2021 ◽

pp. 096032712198941

Author(s):

X-S Liu ◽

X-L Bai ◽

Z-X Wang ◽

S-Y Xu ◽

Y Ma ◽

...

Keyword(s):

Oxidative Stress ◽

Cortical Neuron ◽

Cortical Neurons ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Lactate Dehydrogenase Activity ◽

Primary Mouse ◽

Ldh Release ◽

Neuron Injury ◽

And Oxidative Stress

Objective: To investigate how nuclear factor-E2-related factor 2 (Nrf2) involved in the protective effect of isoflurane (Iso) preconditioning in oxygen glucose deprivation (OGD)-induced cortical neuron injury. Methods: Primary mouse cortical neurons were divided into Control, ML385 (an Nrf2 inhibitor), Iso, Iso + ML385, OGD, ML385 + OGD, Iso + OGD, and Iso + ML385 + OGD groups. Lactate dehydrogenase activity (LDH) release and oxidative stress indexes were quantified. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell viability, Annexin V-FITC/propidium iodide (PI) staining to measure cell apoptosis, dichloro-dihydro-fluorescein diacetate (DCFH-DA) method to test reactive oxygen species (ROS), and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting to evaluate genes and protein expression. Results: Iso preconditioning reduced LDH release and inhibited cell cytotoxicity in OGD-induced cortical neurons, which was abolished by ML385. Iso preconditioning increased the Nrf2 nuclear translocation in cortical neurons. Meanwhile, Iso decreased the OGD-induced apoptosis with the down-regulations of Bax and Caspase-3 and the up-regulation of Bcl-2, which was reversed by ML385. OGD enhanced the level of ROS and malondialdehyde (MDA) in cortical neurons, but reduced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which were aggravated in ML385 + OGD group and mitigated in Iso + OGD group. No observable difference was found between OGD group and Iso + ML385 + OGD group regarding apoptosis-related proteins and oxidative stress-related indexes. Conclusion: Iso preconditioning up-regulated Nrf2 level to play its protective role in OGD-induced mouse cortical neuron injury.

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Overexpression of Transcripts Coding for Renin-b but Not for Renin-a Reduce Oxidative Stress and Increase Cardiomyoblast Survival under Starvation Conditions

Cells ◽

10.3390/cells10051204 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1204

Author(s):

Heike Wanka ◽

Philipp Lutze ◽

Alexander Albers ◽

Janine Golchert ◽

Doreen Staar ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

B Cells ◽

Apoptotic Cell ◽

Renin Angiotensin System ◽

Glucose Deprivation ◽

Protective Effects ◽

Glucose Depletion ◽

A Cells ◽

Apoptosis And Necrosis

A stimulated renin-angiotensin system is known to promote oxidative stress, apoptosis, necrosis and fibrosis. Renin transcripts (renin-b; renin-c) encoding a cytosolic renin isoform have been discovered that may in contrast to the commonly known secretory renin (renin-a) exert protective effects Here, we analyzed the effect of renin-a and renin-b overexpression in H9c2 cardiomyoblasts on apoptosis and necrosis as well as on potential mechanisms involved in cell death processes. To mimic ischemic conditions, cells were exposed to glucose starvation, anoxia or combined oxygen–glucose deprivation (OGD) for 24 h. Under OGD, control cells exhibited markedly increased necrotic and apoptotic cell death accompanied by enhanced ROS accumulation, loss of mitochondrial membrane potential and decreased ATP levels. The effects of OGD on necrosis were exaggerated in renin-a cells, but markedly diminished in renin-b cells. However, with respect to apoptosis, the effects of OGD were almost completely abolished in renin-b cells but interestingly also moderately diminished in renin-a cells. Under glucose depletion we found opposing responses between renin-a and renin-b cells; while the rate of necrosis and apoptosis was aggravated in renin-a cells, it was attenuated in renin-b cells. Based on our results, strategies targeting the regulation of cytosolic renin-b as well as the identification of pathways involved in the protective effects of renin-b may be helpful to improve the treatment of ischemia-relevant diseases.

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Fraxin Prevents Chemically Induced Hepatotoxicity by Reducing Oxidative Stress

Molecules ◽

10.3390/molecules22040587 ◽

2017 ◽

Vol 22 (4) ◽

pp. 587 ◽

Cited By ~ 13

Author(s):

Bo Chang ◽

Young Jung ◽

Chi-Su Yoon ◽

Jun Oh ◽

Jae Hong ◽

...

Keyword(s):

Oxidative Stress ◽

Chemically Induced

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Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model

International Journal of Molecular Sciences ◽

10.3390/ijms22031285 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1285

Author(s):

Seong Soon Kim ◽

Hyemin Kan ◽

Kyu-Seok Hwang ◽

Jung Yoon Yang ◽

Yuji Son ◽

...

Keyword(s):

Oxidative Stress ◽

Epileptic Seizure ◽

Neurological Disorders ◽

Aminobutyric Acid ◽

Oxygen Species ◽

Gamma Aminobutyric Acid ◽

Zebrafish Model ◽

Neuroprotective Effects ◽

Drug Discovery And Development ◽

Spontaneous Seizures

Epilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epileptic zebrafish and mouse models. In this study, we investigated the anti-epileptic effects of GM-90432 through neurochemical profiling-based approach to understand the neuroprotective mechanism in a pentylenetetrazole (PTZ)-induced epileptic seizure zebrafish model. GM-90432 effectively improved PTZ-induced epileptic behaviors via upregulation of 5-hydroxytryptamine, 17-β-estradiol, dihydrotestosterone, progesterone, 5α -dihydroprogesterone, and allopregnanolone levels, and downregulation of normetanephrine, gamma-aminobutyric acid, and cortisol levels in brain tissue. GM-90432 also had a protective effect against PTZ-induced oxidative stress and zebrafish death, suggesting that it exhibits biphasic neuroprotective effects via scavenging of reactive oxygen species and anti-epileptic activities in a zebrafish model. In conclusion, our results suggest that neurochemical profiling study could be used to better understand of anti-epileptic mechanism of GM-90432, potentially leading to new drug discovery and development of anti-seizure agents.

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Subsequent treatment of leafy vegetables with low doses of UVB-radiation does not provoke cytotoxicity, genotoxicity, or oxidative stress in a human liver cell model

Food Bioscience ◽

10.1016/j.fbio.2021.101327 ◽

2021 ◽

pp. 101327

Author(s):

Melanie Wiesner-Reinhold ◽

João Victor Dutra Gomes ◽

Corinna Herz ◽

Hoai Thi Thu Tran ◽

Susanne Baldermann ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Cell ◽

Human Liver ◽

Cell Model ◽

Subsequent Treatment ◽

Leafy Vegetables ◽

Low Doses ◽

Uvb Radiation ◽

Human Liver Cell ◽

Liver Cell Model

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Plasmalogens improve swimming performance by modulating the expression of genes involved in amino acids and lipid metabolism, oxidative stress, and ferroptosis in an Alzheimer's disease zebrafish model

Food & Function ◽

10.1039/d1fo01471d ◽

2021 ◽

Author(s):

Junli Feng ◽

Gongshuai Song ◽

Yuanyuan Wu ◽

Xi Chen ◽

Jie Pang ◽

...

Keyword(s):

Oxidative Stress ◽

Amino Acids ◽

Lipid Metabolism ◽

Human Health ◽

Swimming Performance ◽

Cognitive Impairments ◽

Zebrafish Model ◽

Expression Of Genes ◽

Health Studies ◽

Underlying Mechanisms

Plasmalogens (PLs) are critical to human health. Studies have reported a link between downregulation of PLs levels and cognitive impairments in patients with Alzheimer´s disease (AD). however, the underlying mechanisms...

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Zinc Chloride Exposure Inhibits Brain Acetylcholine Levels, Produces Neurotoxic Signatures, and Diminishes Memory and Motor Activities in Adult Zebrafish

International Journal of Molecular Sciences ◽

10.3390/ijms19103195 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3195 ◽

Cited By ~ 17

Author(s):

Sreeja Sarasamma ◽

Gilbert Audira ◽

Stevhen Juniardi ◽

Bonifasius Sampurna ◽

Sung-Tzu Liang ◽

...

Keyword(s):

Oxidative Stress ◽

Zinc Chloride ◽

Short Term Memory ◽

Amyloid Β ◽

Antioxidant Defense System ◽

Significant Inhibition ◽

Control Group ◽

Adult Zebrafish ◽

Zebrafish Model ◽

Low Concentrations

In this study, we evaluated the acute (24, 48, 72, and 96 h) and chronic (21 days) adverse effects induced by low doses (0.1, 0.5, 1, and 1.5 mg/L) of zinc chloride (ZnCl2) exposure in adult zebrafish by using behavioral endpoints like three-dimensional (3D) locomotion, passive avoidance, aggression, circadian rhythm, and predator avoidance tests. Also, brain tissues were dissected and subjected to analysis of multiple parameters related to oxidative stress, antioxidant responses, superoxide dismutase (SOD), neurotoxicity, and neurotransmitters. The results showed that ZnCl2-exposed fishes displayed decreased locomotor behavior and impaired short-term memory, which caused an Alzheimer’s Disease (AD)-like syndrome. In addition, low concentrations of ZnCl2 induced amyloid beta (amyloid β) and phosphorylated Tau (p-Tau) protein levels in brains. In addition, significant induction in oxidative stress indices (reactive oxygen species (ROS) and malondialdehyde (MDA)), reduction in antioxidant defense system (glutathione (GSH), GSH peroxidase (GSH-Px) and SOD) and changes in neurotransmitters were observed at low concentrations of ZnCl2. Neurotoxic effects of ZnCl2 were observed with significant inhibition of acetylcholine (ACh) activity when the exposure dose was higher than 1 ppm. Furthermore, we found that zinc, metallothionein (MT), and cortisol levels in brain were elevated compared to the control group. A significantly negative correlation was observed between memory and acetylcholinesterase (AChE) activity. In summary, these findings revealed that exposure to ZnCl2 affected the behavior profile of zebrafish, and induced neurotoxicity which may be associated with damaged brain areas related to memory. Moreover, our ZnCl2-induced zebrafish model may have potential for AD-associated research in the future.

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