scholarly journals Neuroprotective Effects of losartan and Captopril in an H2O2- Induced Neurotoxicity Model of Neuro-2A Cells

2021 ◽  
Author(s):  
Negar Firouzabadi ◽  
MohammadReza Kiafar ◽  
Nahid Alimoradi ◽  
Sara Keshtgar ◽  
Fereshteh Mehdipour ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Antihypertensive Drugs ◽  
Cell Damage ◽  
Mental Illnesses ◽  
Ros Generation ◽  
Sod Activity ◽  
Neuroprotective Effects ◽  
Positive Effects ◽  
Intracellular Ca

Abstract Background: Depression is one of the most common mental illnesses and knowledge about its pathophysiology will assist in smart treatment of depression. RAS is a hormonal system that regulates blood pressure and fluid balance. Role of brain RAS has been highlighted in many mental and neurological disorders. Many drugs that target this system, such as ACEIs and ARBs, have shown positive effects on improving depression in clinical studies and animal models.Methods and results: Regarding the effectiveness RAS in depression, this study was conducted to compare the neuroprotective effects of ARB and ACEI drugs and common antidepressants on Neuro-2a cells. The cells were treated in the different concentrations of captopril, losartan, imipramine, and venlafaxine (1, 10, 50, 100 μM), after exposure to H2O2. Intracellular Ca2+ content, cell viability, SOD activity and ROS generation were measured in all groups. Our results show that cell viability of H2O2-treated cells was significantly increased in the presence of antihypertensive drugs. We observed a protective effect against ROS production in all drug groups in Neuro-2a cells. Losartan at all concentrations and captopril prevented cell damage caused by ROS. Cell death due to intracellular Ca2+, was significantly reduced with all antidepressant. At low concentrations of losartan and captopril cell death due to intracellular Ca2+was significantly reduced compared to the H2O2 group. Conclusions: Antihypertensive drugs, especially losartan can have neuroprotective effects and if approved in animal models, it may be used in the future as an adjunct in psychiatric diseases such as depression.

scholarly journals CBIO-07. CELL DEATH INDUCED BY AN OSCILLATING MAGNETIC FIELD IN PATIENT DERIVED GLIOBLASTOMA CELLS IS MEDIATED BY REACTIVE OXYGEN SPECIES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii17-ii17
Author(s):  
Shashank Hambarde ◽  
Martyn Sharpe ◽  
David Baskin ◽  
Santosh Helekar
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cell Viability ◽  
Cortical Neurons ◽  
Reactive Oxygen ◽  
Great Promise ◽  
Antioxidant Vitamin ◽  
Ros Generation ◽  
Oxygen Species ◽  
Novel Therapy

Abstract Noninvasive cancer therapy with minimal side effects would be ideal for improving patient outcome in the clinic. We have developed a novel therapy using strong rotating magnets mounted on a helmet. They generate oscillating magnetic fields (OMF) that penetrate through the skull and cover the entire brain. We have demonstrated that OMF can effectively kill patient derived glioblastoma (GBM) cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes (NHA). Exposure of GBM cells to OMF reduced the cell viability by 33% in comparison to sham-treated cells (p< 0.001), while not affecting NHA cell viability. Time lapse video-microscopy for 16 h after OMF exposure showed a marked elevation of mitochondrial reactive oxygen species (ROS), and rapid apoptosis of GBM cells due to activation of caspase 3. Addition of a potent antioxidant vitamin E analog Trolox effectively blocked OMF-induced GBM cell death. Furthermore, OMF significantly potentiated the cytotoxic effect of the pro-oxidant Benzylamine. The results of our studies demonstrate that OMF-induced cell death is mediated by ROS generation. These results demonstrate a potent oncolytic effect on GBM cells that is novel and unrelated to any previously described therapy, including a very different mechanism of action and different technology compared to Optune therapy. The effect is very powerful, and unlike Optune, can be seen within hours after initiation of treatment. We believe that this technology holds great promise for new, effective and nontoxic treatment of glioblastoma.

scholarly journals Lack of Autophagy Induction by Lithium Decreases Neuroprotective Effects in the Striatum of Aged Rats

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 135
Author(s):  
Angelica Jardim Costa ◽  
Adolfo Garcia Erustes ◽  
Rita Sinigaglia ◽  
Carlos Eduardo Neves Girardi ◽  
Gustavo José da Silva Pereira ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Ultrastructural Changes ◽  
Ros Generation ◽  
Autophagic Flux ◽  
Aged Rats ◽  
Neuroprotective Effects ◽  
Striatal Slices ◽  
Positive Effects ◽  
Age Related ◽  
Neuroprotective Strategy

The pharmacological modulation of autophagy is considered a promising neuroprotective strategy. While it has been postulated that lithium regulates this cellular process, the age-related effects have not been fully elucidated. Here, we evaluated lithium-mediated neuroprotective effects in young and aged striatum. After determining the optimal experimental conditions for inducing autophagy in loco with lithium carbonate (Li2CO3), we measured cell viability, reactive oxygen species (ROS) generation and oxygen consumption with rat brain striatal slices from young and aged animals. In the young striatum, Li2CO3 increased tissue viability and decreased ROS generation. These positive effects were accompanied by enhanced levels of LC3-II, LAMP 1, Ambra 1 and Beclin-1 expression. In the aged striatum, Li2CO3 reduced the autophagic flux and increased the basal oxygen consumption rate. Ultrastructural changes in the striatum of aged rats that consumed Li2CO3 for 30 days included electrondense mitochondria with disarranged cristae and reduced normal mitochondria and lysosomes area. Our data show that the striatum from younger animals benefits from lithium-mediated neuroprotection, while the striatum of older rats does not. These findings should be considered when developing neuroprotective strategies involving the induction of autophagy in aging.

scholarly journals AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao Lin ◽  
Haotuo Ye ◽  
Felix Siaw-Debrah ◽  
Sishi Pan ◽  
Zibin He ◽  
...  
Keyword(s):  
Cell Death ◽  
Intracerebral Hemorrhage ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Neurological Function ◽  
Inflammatory Factors ◽  
Neuroprotective Effects ◽  
Caspase 1 ◽  
Cell Death Pathways ◽  
Cell Death Pathway

Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage. Pyroptosis is a newly discovered cell death pathway that has gained attention in recent years. This pathway mainly depends on activation of caspase-1-mediated cascades to cause cell death. We tested a well-known selective inhibitor of caspase-1, AC-YVAD-CMK, which has previously been found to have neuroprotective effects in ICH mice model, to ascertain its effects on the activation of inflammasomes mediated pyroptosis. Our results showed that AC-YVAD-CMK could reduce caspase-1 activation and inhibit IL-1β production and maturation, but has no effect on NLRP3 expression, an upstream inflammatory complex. AC-YVAD-CMK administration also resulted in reduction in M1-type microglia polarization around the hematoma, while increasing the number of M2-type cells. Furthermore, AC-YVAD-CMK treated mice showed some recovery of neurological function after hemorrhage especially at the hyperacute and subacute stage resulting in some degree of limb movement. In conclusion, we are of the view that AC-YVAD-CMK could inhibit pyroptosis, decrease the secretion or activation of inflammatory factors, and affect the polarization of microglia resulting in improvement of neurological function after ICH.

NEUROPROTECTIVE EFFECTS OF GUARANA (PAULLINIA CUPANA MART.) AGAINST VINCRISTINE IN VITRO EXPOSURE

2017 ◽  
pp. 1-6
Author(s):  
C.F. Veloso ◽  
A.K. Machado ◽  
F.C. Cadoná ◽  
V.F. Azzolin ◽  
I.B.M. Cruz ◽  
...  
Keyword(s):  
Cell Viability ◽  
Monolayer Culture ◽  
Cell Damage ◽  
Neuroprotective Effect ◽  
In Vitro Study ◽  
Oxygen Species ◽  
Neuroprotective Effects ◽  
Hydroalcoholic Extract ◽  
Mice Brain

Background: Vincristine (VCR) is not a specific chemotherapeutic drug, responsible for cause several side effects. In this sense, many natural products have been studied to reduce this problem. Objetives: To examine the guarana neuroprotective effect in mice brain and cerebellum cells against vincristine (VCR) exposition. Design: An in vitro study was performed using mice brain and cerebellum mice in monolayer culture. First, cells were exposed to VCR (0.009 µM for 24 hours and 0.0007 µM for 72 hours) to measure the cytotoxicity effect. Also, the cellular effect of hydroalcoholic extract of guarana (10; 30; 100 and 300 μg/mL) was evaluated in the same cells in 24 and 72 hours. After that, cells were exposed to VCR and guarana extract to evaluate the neuroprotective effect of guarana. Measurements: Cell viability was analyzed by MTT, Free dsDNA and LHD Assays. Moreover, metabolism oxidative profile was evaluated by reactive oxygen species (ROS), lipoperoxidation (LPO) and catalase (CAT) levels through DCFH-DA, TBARS and Catalase Activity Assays, respectively. Results: Our findings revealed that VCR caused neuronal cytotoxicity by reducing cell viability and increasing ROS and LPO levels. On the other hand, guarana did not cause cell damage in none of tested concentrations. In addition, guarana exhibited a notable protective effect on brain and cerebellum cells exposed to VCR by increasing cell viability, stimulating CAT activity, reducing levels of ROS and LPO. Conclusions: In this sense, guaraná is a remarkable antioxidant fruit that could be a target in new therapies development to reduce VCR neurotoxicity.

scholarly journals Effect of cryopreservation on the cellular integrity of equine embryos

Reproduction ◽  
2005 ◽  
Vol 129 (6) ◽  
pp. 789-798 ◽  
Author(s):  
T Tharasanit ◽  
B Colenbrander ◽  
T A E Stout
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Cytochalasin B ◽  
Cell Damage ◽  
Uterine Cavity ◽  
Trypsin Treatment ◽  
Embryo Survival ◽  
Embryo Size ◽  
Cellular Integrity ◽  
Cytoskeleton Integrity

Horse embryos are rarely cryopreserved in practice because expanded blastocysts tolerate freezing poorly, and the embryo begins expanding very soon after entering the uterine cavity. This study examined the effects of freezing on cytoskeleton integrity, and investigated whether cell damage could be reduced using trypsin to thin the blastocyst capsule or cytochalasin-B (cyto-B) to stabilise the cytoskeleton. Sixty-nine embryos were recovered 7 days after ovulation and equilibrated in 10% glycerol, with or without pretreatment with 0.2% trypsin or 7.5 μg/ml cyto-B. Forty-two of the embryos were frozen; the rest were used to determine whether pre-freezing treatment alone caused cell damage. Subsequently, embryos were stained with 4′,6-diamidino-2-phenylindole dihydrochloride, to identify dead cells, and fluorescently labelled phalloidin, to assess cytoskeleton quality. Without freezing, none of the treatments affected cell viability. And although Cyto-B altered actin distribution, the cytoskeleton returned to normal during a 4-h culture. Following cryopreservation, the percentage of dead cells (11.1 ± 1.3%) did not differ between treatments (P > 0.05), but significantly fewer cells died in small (≤300 μm) than in large embryos when neither pretreatment was used (P > 0.05); the effect of embryo size was, however, not significant after pretreatment with trypsin or cyto-B, and trypsin improved the likelihood of an intact cytoskeleton post thaw. However, trypsin treatment also resulted in a ‘sticky’ capsule that complicated embryo handling, and cyto-B-induced actin-depolymerisation was not reversed during a 6-h post-thaw incubation. Thus, while trypsin pretreatment improved cytoskeleton preservation and both trypsin and cyto-B may reduce cell death during cryopreservation of large embryos, both treatments induced other changes likely to compromise embryo survival.

scholarly journals Pinus thunbergii Parl. Extracts Reduce Acute Inflammation by Targeting Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Chan Jong Yoon ◽  
Won Seok Choi ◽  
Hyun Sik Kang ◽  
Hong Jo Kim ◽  
Wang Tae Lee ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Cell Damage ◽  
Pinus Thunbergii ◽  
Ros Generation ◽  
No Production ◽  
Ros Scavenging ◽  
Sod Activity ◽  
Edema Formation ◽  
Cox 2 ◽  
Anti Inflammatory

Pinus thunbergii Parl. (PTP) has traditionally been used for edible and medicinal purposes to treat several disorders, including diabetes and neuralgia. Therefore, this study sought to evaluate the inhibitory effects of PTP leaf ethanol extracts on acute inflammation. Moreover, the reactive oxygen species (ROS) scavenging activity, superoxide dismutase (SOD) activity, lipopolysaccharide (LPS)-induced nitric oxide (NO) generation, and H2O2-induced lipid peroxidation capacity of PTP were assessed in vitro in RAW 264.7 macrophages. Our results suggest that PTP prevents cell damage caused by oxidative free radicals and downregulates the expression of LPS-induced inflammation-associated factors including inducible nitric oxidase synthetase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). PTP inhibited NO production by 53.5% ( P < 0.05 ) and iNOS expression by 71.5% ( P < 0.01 ) at 100 µg/mL. PTP at 100 µg/mL also inhibited ROS generation by 58.2% ( P < 0.01 ) and SOD activity by 29.3%, as well as COX-2 expression by 83.3% ( P < 0.01 ) and PGE2 expression by 98.6% ( P < 0.01 ). The anti-inflammatory effects of PTP were confirmed in vivo using an arachidonic acid (AA)-induced ear edema mouse model. Ear thickness and myeloperoxidase (MPO) activity were evaluated as indicators of inflammation. PTP inhibited edema formation by 64.5% ( P < 0.05 ) at 1.0 mg/ear. A total of 16 metabolites were identified in PTP extracts and categorized into subgroups, including two phenolic acids (mainly quinic acid), seven flavonoids, five lignans, one sesquiterpenoid, and one long-chain fatty acid. Therefore, our results suggest that PTP possesses anti-inflammatory properties.

scholarly journals ROS-Mediated Necroptosis Is Involved in Iron Overload-Induced Osteoblastic Cell Death

2020 ◽  
Vol 2020 ◽  
pp. 1-22 ◽  
Author(s):  
Qing Tian ◽  
Bo Qin ◽  
Yufan Gu ◽  
Lijun Zhou ◽  
Songfeng Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Iron Overload ◽  
Mitochondrial Permeability Transition ◽  
Cell Damage ◽  
Critical Role ◽  
Osteoblastic Cells ◽  
Osteoblastic Cell ◽  
Ros Generation ◽  
Mptp Opening

Excess iron has been reported to lead to osteoblastic cell damage, which is a crucial pathogenesis of iron overload-related osteoporosis. However, the cytotoxic mechanisms have not been fully documented. In the present study, we focused on whether necroptosis contributes to iron overload-induced osteoblastic cell death and related underlying mechanisms. Here, we showed that the cytotoxicity of iron overload in osteoblastic cells was mainly due to necrosis, as evidenced by the Hoechst 33258/PI staining, Annexin-V/PI staining, and transmission electronic microscopy. Furthermore, we revealed that iron overload-induced osteoblastic necrosis might be mediated via the RIPK1/RIPK3/MLKL necroptotic pathway. In addition, we also found that iron overload was able to trigger mitochondrial permeability transition pore (mPTP) opening, which is a critical downstream event in the execution of necroptosis. The key finding of our experiment was that iron overload-induced necroptotic cell death might depend on reactive oxygen species (ROS) generation, as N-acetylcysteine effectively rescued mPTP opening and necroptotic cell death. ROS induced by iron overload promote necroptosis via a positive feedback mechanism, as on the one hand N-acetylcysteine attenuates the upregulation of RIPK1 and RIPK3 and phosphorylation of RIPK1, RIPK3, and MLKL and on the other hand Nec-1, siRIPK1, or siRIPK3 reduced ROS generation. In summary, iron overload induced necroptosis of osteoblastic cells in vitro, which is mediated, at least in part, through the RIPK1/RIPK3/MLKL pathway. We also highlight the critical role of ROS in the regulation of iron overload-induced necroptosis in osteoblastic cells.

Unfolded Protein Response is Involved in Trans-Platinum (II) Complex-Induced Apoptosis in Prostate Cancer Cells via ROS Accumulation

2019 ◽  
Vol 19 (9) ◽  
pp. 1184-1195
Author(s):  
Didem Karakas ◽  
Buse Cevatemre ◽  
Arzu Y. Oral ◽  
Veysel T. Yilmaz ◽  
Engin Ulukaya
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cell Viability ◽  
Er Stress ◽  
Apoptotic Cell ◽  
Annexin V ◽  
Treatment Modalities ◽  
Drug Candidate ◽  
Ros Generation ◽  
Dependent Manner

Background:Prostate cancer is one of the most common cancer types and it is the sixth leading cause of cancer-related death in men worldwide. Even though novel treatment modalities have been developed, it still a lifethreatening disease. Therefore novel compounds are needed to improve the overall survival.Methods:In our study, it was aimed to evaluate the anti-cancer activity of newly synthesized Platinum (II) [Pt(II)] complex on DU145, LNCaP and PC-3 prostate cancer cell lines. The cytotoxic activity of Pt(II) complex was tested by SRB and ATP cell viability assays. To detect the mode of cell death; fluorescent staining, flow cytometry and western blot analyses were performed.Results:The Pt(II) complex treatment resulted in a decrease in cell viability and increasing levels of apoptotic markers (pyknotic nuclei, annexin-V, caspase 3/7 activity) and a decrease in mitochondrial membrane potential in a dose dependent manner. Among cell types, tested PC-3 cells were found to be more sensitive to Pt(II) complex, demonstrating elevation of DNA damage in this cell line. In addition, Pt(II) complex induced Endoplasmic Reticulum (ER) stress by triggering ROS generation. More importantly, pre-treatment with NAC alleviated Pt(II) complex-mediated ER stress and cell death in PC-3.Conclusion:These findings suggest an upstream role of ROS production in Pt(II) complex-induced ER stressmediated apoptotic cell death. Considering the ROS-mediated apoptosis inducing the effect of Pt(II) complex, it warrants further evaluation as a novel metal-containing anticancer drug candidate.

scholarly journals Neuroprotective Effects of Cuscutae Semen in a Mouse Model of Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Minsook Ye ◽  
Seul gi Lee ◽  
Eun Sook Chung ◽  
Su-jin Lim ◽  
Won Seob Kim ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Glutathione Peroxidase ◽  
Pc12 Cells ◽  
Statistical Significance ◽  
Inhibitory Effect ◽  
Ros Generation ◽  
Neuroprotective Effects ◽  
Differentiated Pc12 Cells

Parkinson’s disease (PD) is a neurodegenerative movement disorder that is characterized by the progressive degeneration of the dopaminergic (DA) pathway. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes damage to the DA neurons, and 1-4-methyl-4-phenylpyridinium (MPP+) causes cell death in differentiated PC12 cells that is similar to the degeneration that occurs in PD. Moreover, MPTP treatment increases the activity of the brain’s immune cells, reactive oxygen species- (ROS-) generating processes, and glutathione peroxidase. We recently reported that Cuscutae Semen (CS), a widely used traditional herbal medicine, increases cell viability in a yeast model of PD. In the present study, we examined the inhibitory effect of CS on the neurotoxicity of MPTP in mice and on the MPP+-induced cell death in differentiated PC12 cells. The MPTP-induced loss of nigral DA neurons was partly inhibited by CS-mediated decreases in ROS generation. The activation of microglia was slightly inhibited by CS, although this effect did not reach statistical significance. Furthermore, CS may reduce the MPP+ toxicity in PC12 cells by suppressing glutathione peroxidase activation. These results suggest that CS may be beneficial for the treatment of neurodegenerative diseases such as PD.

scholarly journals SIRT3-SOD2-ROS pathway is involved in Linalool-induced glioma cell apoptotic death

2017 ◽  
Vol 64 (2) ◽  
Author(s):  
Yanhao Cheng ◽  
Chao Dai ◽  
Jian Zhang
Keyword(s):  
Cell Death ◽  
Protein Expression ◽  
Cell Viability ◽  
Glioma Cell ◽  
Apoptotic Cell ◽  
Immunoblot Analysis ◽  
Apoptotic Cell Death ◽  
Dependent Manner ◽  
Sod Activity ◽  
Mrna And Protein Expression

Glioma is the most prevalent type of adult primary brain tumor and chemotherapy of glioma was limited by drug-resistance. Linalool is an acyclic monoterpene alcohol possessing various pharmacological activities. The present study was conducted to evaluate the effect of Linalool on glioma cell growth. The effect of Linalool on U87-MG cells was investigated and the results showed that Linalool significantly reduced cell viability in U87-MG cells in a concentration and time-dependent manner. In addition, exposure of cells to Linalool resulted in concentration-dependent increase of TUNEL-stained cells, indicating the occurrence of apoptotic cell death. Linalool decreased mitochondrial oxygen consumption rate, increased the expression of Bax and Bcl-2, reduced the expression of Bcl-2 and Bcl-xl, and increased the activities of caspase 3 and caspase 9, leading to increase of apoptosis. Linalool resulted in a concentration-dependent decrease of SOD activity but had no significant effect on the mRNA and protein expression of SOD2. Moreover, Linalool resulted in a significant increase of acetylated SOD2. The mRNA and protein expression of SIRT3 was significantly inhibited by Linalool. Immunoblot analysis showed that there were protein/protein interaction of SOD2 and SIRT3 in control U87-MG cells. Linalool treatment significantly decreased the interaction of SOD2 and SIRT3. Overexpression of SIRT3 significantly inhibited Linalool-induced increase of mitochondrial ROS level, apoptotic cell death and decrease of cell viability. In summary, we found that Linalool exhibited inhibitory effect on glioma cells through regulation of SIRT3-SOD2-ROS signaling.

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