scholarly journals Thunbergia laurifolia Leaf Extract Inhibits Glutamate-Induced Neurotoxicity and Cell Death through Mitophagy Signaling

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1678
Author(s):  
Wudtipong Vongthip ◽  
Chanin Sillapachaiyaporn ◽  
Kyu-Won Kim ◽  
Monruedee Sukprasansap ◽  
Tewin Tencomnao
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Antioxidant Enzymes ◽  
Neuronal Death ◽  
Leaf Extract ◽  
Mitochondrial Protein ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
Thunbergia Laurifolia

Oxidative stress plays a crucial role in neurodegeneration. Therefore, reducing oxidative stress in the brain is an important strategy to prevent neurodegenerative disorders. Thunbergia laurifolia (Rang-jued) is well known as an herbal tea in Thailand. Here, we aimed to determine the protective effects of T. laurifolia leaf extract (TLE) on glutamate-induced oxidative stress toxicity and mitophagy-mediated cell death in mouse hippocampal cells (HT-22). Our results reveal that TLE possesses a high level of bioactive antioxidants by LC–MS technique. We found that the pre-treatment of cells with TLE prevented glutamate-induced neuronal death in a concentration-dependent manner. TLE reduced the intracellular ROS and maintained the mitochondrial membrane potential caused by glutamate. Moreover, TLE upregulated the gene expression of antioxidant enzymes (SOD1, SOD2, CAT, and GPx). Interestingly, glutamate also induced the activation of the mitophagy process. However, TLE could reverse this activity by inhibiting autophagic protein (LC3B-II/LC3B-I) activation and increasing a specific mitochondrial protein (TOM20). Our results suggest that excessive glutamate can cause neuronal death through mitophagy-mediated cell death signaling in HT-22 cells. Our findings indicate that TLE protects cells from neuronal death by stimulating the endogenous antioxidant enzymes and inhibiting glutamate-induced oxidative toxicity via the mitophagy–autophagy pathway. TLE might have potential as an alternative or therapeutic approach in neurodegenerative diseases.

scholarly journals Antioxidant Properties of Fucoidan Alleviate Acceleration and Exacerbation of Hippocampal Neuronal Death Following Transient Global Cerebral Ischemia in High-Fat Diet-Induced Obese Gerbils

2019 ◽  
Vol 20 (3) ◽  
pp. 554 ◽  
Author(s):  
Ji Ahn ◽  
Myoung Shin ◽  
Dae Kim ◽  
Hyunjung Kim ◽  
Minah Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Antioxidant Enzymes ◽  
Cerebral Ischemia ◽  
Neuronal Death ◽  
High Fat Diet ◽  
Antioxidant Properties ◽  
Global Cerebral Ischemia ◽  
High Fat ◽  
Transient Global Cerebral Ischemia

Fucoidan, a natural sulfated polysaccharide, displays various biological activities including antioxidant properties. We examined the neuroprotective effect of fucoidan against transient global cerebral ischemia (tGCI) in high-fat diet (HFD)-induced obese gerbils and its related mechanisms. Gerbils received HFD for 12 weeks and fucoidan (50 mg/kg) daily for the last 5 days during HFD exposure, and they were subjected to 5-min tGCI. Pyramidal cell death was observed only in the CA 1 area (CA1) of the hippocampus in non-obese gerbils 5 days after tGCI. However, in obese gerbils, pyramidal cell death in the CA1 and CA2/3 occurred at 2 days and 5 days, respectively, after tGCI. In the obese gerbils, oxidative stress indicators (dihydroethidium, 8-hydroxyguanine and 4-hydroxy-2-nonenal) were significantly enhanced and antioxidant enzymes (SOD1 and SOD2) were significantly reduced in pre- and post-ischemic phases compared to the non-obese gerbils. Fucoidan treatment attenuated acceleration and exacerbation of tGCI-induced neuronal death in the CA1–3, showing that oxidative stress was significantly reduced, and antioxidant enzymes were significantly increased in pre- and post-ischemic phases. These findings indicate that pretreated fucoidan can relieve the acceleration and exacerbation of ischemic brain injury in an obese state via the attenuation of obesity-induced severe oxidative damage.

scholarly journals TrxR2 overexpression alleviates inflammation-mediated neuronal death via reducing the oxidative stress and activating the Akt–Parkin pathway

2019 ◽  
Vol 8 (5) ◽  
pp. 641-653 ◽  
Author(s):  
Jinbao Gao ◽  
Yunjun Li ◽  
Wende Li ◽  
Haijiang Wang
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Viability ◽  
Western Blotting ◽  
Neuronal Death ◽  
Protective Effects ◽  
Mitochondrial Apoptosis ◽  
Inflammation Response ◽  
N2a Cells

Abstract Neuronal death caused by inflammatory cytokine-mediated neuroinflammation is being extensively explored. Thioredoxin reductase (TrxR) 2 is a novel mediator of inflammation response. In the current study, we focus on the mechanisms of TrxR2 overexpression in inflammation-mediated neuronal death. LPS was used to induce neuroinflammation in N2a cells in vitro. Adenovirus-loaded TrxR2 was transfected into N2a cells to up-regulate TrxR2 expression. Then, cell viability was determined via MTT assay and TUNEL assay. Apoptosis was measured via western blotting and ELISA. Oxidative stress was detected via ELISA and flow cytometry. A pathway inhibitor was used to verify the role of the Akt–Parkin pathway in the LPS-mediated N2a cell death in the presence of TrxR2 overexpression. With the help of immunofluorescence assay and western blotting, we found that TrxR2 expression was significantly reduced in response to LPS treatment, and this effect was associated with N2a cell death via apoptosis. At the molecular level, TrxR2 overexpression elevated the activity of the Akt–Parkin pathway, as evidenced by the increased expression of p-Akt and Parkin. Interestingly, inhibition of the Akt–Parkin pathway abolished the regulatory effect of TrxR2 on LPS-treated N2a cells, as evidenced by the decreased cell viability and increased apoptotic ratio. Besides, TrxR2 overexpression also reduced oxidative stress, inflammation factor transcription and mitochondrial apoptosis. However, inhibition of Akt–Parkin axis abrogated the protective effects of TrxR2 on redox balance, mitochondrial performance and cell survival. LPS-mediated neuronal death was linked to a drop in TrxR2 overexpression and the inactivation of the Akt–Parkin pathway. Overexpression of TrxR2 sustained mitochondrial function, inhibited oxidative stress, repressed inflammation response, and blocked mitochondrial apoptosis, finally sending a pro-survival signal for the N2a cells in the setting of LPS-mediated inflammation environment.

scholarly journals Antioxidant activity of pineal methoxyindoles on hepatocyte plasmatic membrane

2019 ◽  
Vol 2 (1) ◽  
pp. 161-174
Author(s):  
Marcos C Reyes-Gonzales ◽  
Eduardo Esteban-Zubero ◽  
Laura López-Pingarrón ◽  
María Soledad Soria ◽  
Desiree Pereboom ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Membrane ◽  
Membrane Fluidity ◽  
Membrane Lipid ◽  
Hydroxyl Group ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
Plasmatic Membrane ◽  
Membrane Rigidity

Antioxidant effect of several pineal derived molecules has been well documented. Here, the protective effects of 5-methoxytryptophol (5-MTOH) and 5-methoxyindol-3-acetic acid (5-MIAA) on hepatic cell membrane lipid peroxidation and cell membrane rigidity induced by FeCl3 plus ascorbic acid have been systemically investigated. The membrane fluidity was evaluated by fluorescence spectroscopy, malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations and carbonyl groups of protein were measured as the parameters of lipid and protein damage, respectively. Results showed that oxidative stress increased membrane rigidity, MDA and 4-HDA concentrations as well as carbonyl content in a concentration-dependent manner. 5-MTOH, but not 5-MIAA, significantly attenuated these oxidative indecies. In absence of oxidative stress, none of these methoxyindoleamines modified the content of MDA, 4-HDA or carbonylation. However 5-MIAA at its highest concentration slightly modified membrane fluidity. The results suggest that structural modification of C3 in the methoxyindoleamine, that is, the carboxyl group replaced by hydroxyl group in this site could improve the ability of 5-methoxyindoleamine derivatives to preserve membrane fluidity of cells which are under oxidative stress. 

scholarly journals MicroRNA-223-3p Protect Against Radiation-Induced Cardiac Toxicity by Alleviating Myocardial Oxidative Stress and Programmed Cell Death via Targeting the AMPK Pathway

2022 ◽  
Vol 9 ◽  
Author(s):  
Dao-ming Zhang ◽  
Jun-jian Deng ◽  
Yao-gui Wu ◽  
Tian Tang ◽  
Lin Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Myocardial Injury ◽  
Adenosine Monophosphate ◽  
Dependent Manner ◽  
Protective Effects ◽  
Compound C ◽  
Myocardial Oxidative Stress ◽  
Radiation Induced

Objectives: Radiotherapy improves the survival rate of cancer patients, yet it also involves some inevitable complications. Radiation-induced heart disease (RIHD) is one of the most serious complications, especially the radiotherapy of thoracic tumors, which is characterized by cardiac oxidative stress disorder and programmed cell death. At present, there is no effective treatment strategy for RIHD; in addition, it cannot be reversed when it progresses. This study aims to explore the role and potential mechanism of microRNA-223-3p (miR-223-3p) in RIHD.Methods: Mice were injected with miR-223-3p mimic, inhibitor, or their respective controls in the tail vein and received a single dose of 20 Gy whole-heart irradiation (WHI) for 16 weeks after 3 days to construct a RIHD mouse model. To inhibit adenosine monophosphate activated protein kinase (AMPK) or phosphodiesterase 4D (PDE4D), compound C (CompC) and AAV9-shPDE4D were used.Results: WHI treatment significantly inhibited the expression of miR-223-3p in the hearts; furthermore, the levels of miR-223-3p decreased in a radiation time-dependent manner. miR-223-3p mimic significantly relieved, while miR-223-3p inhibitor aggravated apoptosis, oxidative damage, and cardiac dysfunction in RIHD mice. In addition, we found that miR-223-3p mimic improves WHI-induced myocardial injury by activating AMPK and that the inhibition of AMPK by CompC completely blocks these protective effects of miR-223-3p mimic. Further studies found that miR-223-3p lowers the protein levels of PDE4D and inhibiting PDE4D by AAV9-shPDE4D blocks the WHI-induced myocardial injury mediated by miR-223-3p inhibitor.Conclusion: miR-223-3p ameliorates WHI-induced RIHD through anti-oxidant and anti-programmed cell death mechanisms via activating AMPK by PDE4D regulation. miR-223-3p mimic exhibits potential value in the treatment of RIHD.

scholarly journals The anti-malarial drug atovaquone potentiates platinum-mediated cancer cell death by increasing oxidative stress

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
James T. T. Coates ◽  
Gonzalo Rodriguez-Berriguete ◽  
Rathi Puliyadi ◽  
Thomas Ashton ◽  
Remko Prevo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cancer Cell ◽  
Tumor Hypoxia ◽  
Specific Inhibitor ◽  
Cytotoxic Agents ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cancer Cell Death

Abstract Platinum chemotherapies are highly effective cytotoxic agents but often induce resistance when used as monotherapies. Combinatorial strategies limit this risk and provide effective treatment options for many cancers. Here, we repurpose atovaquone (ATQ), a well-tolerated & FDA-approved anti-malarial agent by demonstrating that it potentiates cancer cell death of a subset of platinums. We show that ATQ in combination with carboplatin or cisplatin induces striking and repeatable concentration- and time-dependent cell death sensitization in vitro across a variety of cancer cell lines. ATQ induces mitochondrial reactive oxygen species (mROS), depleting intracellular glutathione (GSH) pools in a concentration-dependent manner. The superoxide dismutase mimetic MnTBAP rescues ATQ-induced mROS production and pre-loading cells with the GSH prodrug N-acetyl cysteine (NAC) abrogates the sensitization. Together, these findings implicate ATQ-induced oxidative stress as key mediator of the sensitizing effect. At physiologically achievable concentrations, ATQ and carboplatin furthermore synergistically delay the growth of three-dimensional avascular spheroids. Clinically, ATQ is a safe and specific inhibitor of the electron transport chain (ETC) and is concurrently being repurposed as a candidate tumor hypoxia modifier. Together, these findings suggest that ATQ is deserving of further study as a candidate platinum sensitizing agent.

Protective Effect of Alpha-Tocopherol in Deltamethrin Induced Immunotoxicity

2019 ◽  
Vol 19 (2) ◽  
pp. 171-184 ◽  
Author(s):  
Anoop Kumar ◽  
Ruchika Sharma ◽  
Divya Rana ◽  
Neelima Sharma
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Active Form ◽  
Alpha Tocopherol ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Immune Functions ◽  
Biological Functions ◽  
Concentration Dependent Manner ◽  
Early Markers

Background and Objective: α-Tocopherol is the active form of vitamin E which has various biological functions. However, the exact molecular mechanism of its action is not fully understood. Thus, the main objective of the current study is to determine the contribution of α-tocopherol in counteraction of the apoptogenic signaling pathways induced by deltamethrin in murine thymocytes and splenocytes. </P><P> Methods and Results: Deltamethrin (25 µM) induces apoptosis at 18 h through the activation of reactive oxygen species, caspases and depletion of glutathione in thymocytes and splenocytes. MTT assay results have shown that α-tocopherol (10 and 50 µg/ml) when added along with Deltamethrin (25µM), increases the viability of thymocytes and splenocytes in a concentration-dependent manner. The α-tocopherol treatment reduces the early markers of cell death (ROS and caspase3 activation) significantly. Further, the depleted GSH by deltamethrin has also been restored by α-tocopherol. At 18 h, α-tocopherol (50 µg/ml) significantly reduced the Deltamethrin induced cell death. In additional, phenotyping and cytokines assay have demonstrated that alpha-tocopherol significantly ameliorated the altered immune functions. Conclusion: These findings indicate that α-tocopherol shows immunoprotective effects in Deltamethrin induced splenic and thymic apoptosis by inhibiting oxidative stress and caspasedependent apoptogenic pathways.

scholarly journals Antioxidative Potential of Garlic on Lead-Induced Oxidative Stress and Effect on Enzyme Activity in Rice Plants

2018 ◽  
pp. 79-83
Author(s):  
Tugbobo Oladimeji S ◽  
Idowu Kayode S ◽  
Ajao Oluwaseyi I
Keyword(s):  
Oxidative Stress ◽  
Enzyme Activity ◽  
Antioxidant Enzymes ◽  
Lead Acetate ◽  
Lipid Peroxides ◽  
Garlic Extract ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Rice Plants ◽  
Antioxidant Defense Systems

Seedling of Ofada rice (Oryza sativum L) were raised in sand (swampy) and clay (upland) cultures under 500mg/kg lead acetate and 500mg/kg garlic aqueous extract for 40-days. The uptake and distribution pattern of lead with possible induction of oxidative stress and likely alteration in the inherent antioxidant defense systems of the rice plants were determined. The inhibitory potential of garlic against lead-induced oxidative stress in rice seedling was also assessed. From the results, rice seedlings grown for 10-40 days under 500mg/kg lead acetate showed significant (P<0.05) increase in level of lipid peroxides in roots, indicating enhanced lipid peroxidation compared to control. However, incubation of garlic extract with supernatants of rice root and shoot caused a significant (P<0.05) reduction in the accumulation of lipid peroxides in a concentration dependent manner. In addition, there was a marked increase in antioxidant enzymes activities in lead acetate treated seedlings, where the shoot maintained higher defensive enzyme activity than roots. The results suggest that lead-induced oxidative stress could be salvaged by garlic extract and antioxidant enzymes are biomarkers for lead-induced oxidative injury in rice plants.

Effects of Cadmium on the Expression of Antioxidant Enzymes, Oxidative Stress and Apoptosis in Primary Hepatocytes of Carassius Auratus

2012 ◽  
Vol 518-523 ◽  
pp. 341-346
Author(s):  
Shun Yao Jiang ◽  
Pei Jiang Zhou
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Carassius Auratus ◽  
Liver Toxicity ◽  
Control Group ◽  
Dependent Manner ◽  
Primary Hepatocytes ◽  
High Concentration ◽  
Dna Ladder ◽  
Concentration Dependent Manner

The primary hepatocytes of Carassius auratus were incubated with 0, 0.01, 0.1, 1, 10 and 100 mg/l Cadmium(Cd2+) at 25°C for 8h in vitro. The results showed that the hepatocytes survival rate in the 1, 10 and 100 mg/l Cd2+ treated groups were significantly lower than that in the control, the percentage of apoptotic hepatocytes significantly increased in 0.1, 1 and 10 mg/l of Cd2+ treated groups, intracellular reactive oxygen species(ROS) and malondialdehyde (MDA) content significantly increased in 0.1, 1, 10 and 100 mg/l Cd2+ treated groups, typical DNA ladder was observed in 0.1, 1 and 10 mg/l Cd2+ treated groups, and ruleless DNA fragment occurred in 100 mg/l Cd2+ treated group. The activities of the antioxidant enzymes and the expression of their isozymes activities have similar change tendency, compared with the control group, the activities of superoxide dismutase (SOD) and their isozymes were activated by low concentration of Cd2+ (0.1 and 1 mg/l), however, their activities were inhibited by high concentration of Cd2+ (10 and 100 mg/l), especially, the special isozyme (SOD1) was found in the patterns of SOD isozymes in 0.1 and 1 mg/l Cd2+ treated groups, the activities of peroxidase(POD) and its isozymes significantly reduced with a concentration-dependent manner in all Cd Cd2+ treated groups, the activities of catalase(CAT) and its isozymes significantly decreased in higher concentration Cd2+ treated groups (1, 10 and 100mg/l). The results suggested that Cd2+ could damage the activities of the antioxidant enzymes and cause oxidative stress, lipid peroxidation, DNA fragmentation, apoptosis and necrosis in primary hepatocytes, contributing to the liver toxicity induced by Cd2+.

scholarly journals Human Neuronal Cell Lines as An In Vitro Toxicological Tool for the Evaluation of Novel Psychoactive Substances

2021 ◽  
Vol 22 (13) ◽  
pp. 6785
Author(s):  
Valeria Sogos ◽  
Paola Caria ◽  
Clara Porcedda ◽  
Rafaela Mostallino ◽  
Franca Piras ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell ◽  
In Vitro Study ◽  
Dependent Manner ◽  
Novel Psychoactive Substances ◽  
Psychoactive Substances ◽  
Concentration Dependent Manner ◽  
Mechanisms Of Toxicity ◽  
Neuronal Cell Lines

Novel psychoactive substances (NPS) are synthetic substances belonging to diverse groups, designed to mimic the effects of scheduled drugs, resulting in altered toxicity and potency. Up to now, information available on the pharmacology and toxicology of these new substances is very limited, posing a considerable challenge for prevention and treatment. The present in vitro study investigated the possible mechanisms of toxicity of two emerging NPS (i) 4′-methyl-alpha-pyrrolidinoexanophenone (3,4-MDPHP), a synthetic cathinone, and (ii) 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA), a phenethylamine. In addition, to apply our model to the class of synthetic opioids, we evaluated the toxicity of fentanyl, as a reference compound for this group of frequently abused substances. To this aim, the in vitro toxic effects of these three compounds were evaluated in dopaminergic-differentiated SH-SY5Y cells. Following 24 h of exposure, all compounds induced a loss of viability, and oxidative stress in a concentration-dependent manner. 2-Cl-4,5-MDMA activates apoptotic processes, while 3,4-MDPHP elicits cell death by necrosis. Fentanyl triggers cell death through both mechanisms. Increased expression levels of pro-apoptotic Bax and caspase 3 activity were observed following 2-Cl-4,5-MDMA and fentanyl, but not 3,4-MDPHP exposure, confirming the different modes of cell death.

Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes

1998 ◽  
Vol 274 (1) ◽  
pp. C245-C252 ◽  
Author(s):  
Junsuke Igarashi ◽  
Masashi Nishida ◽  
Shiro Hoshida ◽  
Nobushige Yamashita ◽  
Hiroaki Kosaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiac Myocytes ◽  
Myocardial Injury ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
No Donor ◽  
Oxide Synthase ◽  
Gpx Activity

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined. Interleukin-1β induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS,l-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso- N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2(0.1 mM, 1 h). Inhibition of iNOS with Nω-nitro-l-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.

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