scholarly journals NEUROPROTECTIVE EFFECT OF ARTOCARPUS LAKOOCHA EXTRACT AND OXYRESVERATROL AGAINST HYDROGEN PEROXIDE-INDUCED TOXICITY IN SH-SY5Y CELLS

Author(s):  
Hasriadi . ◽  
Matusorn Wong-on ◽  
Phakhamon Lapphanichayakool ◽  
Nanteetip Limpeanchob

Objective: Artocarpus lakoocha Roxb. is a traditional medical plant native to Southeast Asia and used as a dried aqueous extract so-called puag haad. Its role (and its major ingredient, oxyresveratrol) as an antioxidant neuroprotectant were explored.Methods: Differentiated SH-SY5Y neuroblastoma cells in 96-well plates were challenged with 200 µM H2O2 for 4 h and either Trolox (100 µM), oxyresveratrol (5-100 µM), or puag haad (1.2-25 µg/ml) applied 2 h before H2O2 or for 20 h after H2O2 washout. Cell viability, mitochondrial function, intracellular ROS, and lipid peroxidation were assessed.Results: Continuous presence of both H2O2 and antioxidant reduced mitochondrial function by ~50% but only by 30% with antioxidant. Sustained 24 h H2O2 showed no recoveries with antioxidants. Cell viability was modestly restored when antioxidants accompanied H2O2 for 4 h and both washed for another 20 h, but little recovery of mitochondrial function even though antioxidants removed ROS and prevent lipid peroxidation. Antioxidants added for 20 h after H2O2 marginally improve mitochondria and modestly restore cell viability, but lipid peroxidation was completely reversed.Conclusion: These results show that mitochondrial protection was illusive, yet both tested compounds, puag haad and oxyresveratrol, improved cell viability and especially ROS levels and lipid peroxidation. The potency oxyresveratrol on the redox-sensitive expression of antioxidant enzymes and its pharmacokinetics suggests that oral puag haad could provide effective protection in transient neurodegenerative disease. 

Author(s):  
Mohammad Shokrzadeh ◽  
Hashem Javanmard ◽  
Golpar Golmohammad Zadeh ◽  
Hossein Asgarian Omran ◽  
Mona Modanlou ◽  
...  

Introduction: Parkinson disease (PD) is the second most common neurodegenerative disease affecting older individuals with signs of motor disability and cognitive impairment. Epicatechin (EC) and edaravone have neuroprotective effects most probably due to their antioxidant activity; however, a limited number of studies have considered their role in PD. This research aimed at investigating the neuroprotective effect of EC and edaravone in a neurotoxin-induced model of PD. Methods: An in vitro model of PD was made by subjecting SH-SY5Y neuroblastoma cells to neurotoxin: 6-hydroxydopamine (6-OHDA) 100 µM/well. The cytoprotective effect of EC and edaravone in five concentrations on cell viability was tested using the MTT assay. The apoptotic assay was done by annexin V and propidium iodide method using flow cytometry. Results: According to the MTT assay analysis, EC and edaravone had protective effects against 6-OH DA-induced cytotoxicity in SH-SY5Y neuroblastoma cells that were much more significant for edaravone and also a relative synergistic effect between EC and edaravone was observed. The apoptotic analysis showed that edaravone alone could decrease early and late apoptosis, whereas EC diminished early apoptosis, but enhanced late apoptosis and necrosis. Besides, co-treatment of edaravone and EC had a synergistic effect on decreasing apoptosis and increasing cell viability. Conclusion: The protective effect of edaravone on apoptosis and cytotoxicity was demonstrated clearly and EC had a synergistic effect with edaravone.


2020 ◽  
Author(s):  
Shih-Yi Lee ◽  
Shao-Tung Wu ◽  
Ming-Jai Su ◽  
Yao-Jen Liang ◽  
Hui-Chun Ku

Abstract Background: Oxidative stress is an imbalance between the production of reactive oxygen species (ROS) and the detoxification ability of reactive intermediates. It will lead to mitochondrial damage and dysfunction, resulting in the dysfunction of bioenergetic control and loss of ATP production, which is contributed to the pathogenesis of cardiac diseases. Dipeptidyl peptidase-4 (DPP4) is a transmembrane glycoprotein ubiquitously expressed and has multifunctional properties. DPP4 inhibitors are a class of oral diabetes drugs that inhibit the enzyme activity. In addition to its enzymatic property, considerably less is known regarding the nonenzymatic function of DPP4.Methods: We knocked down DPP4 gene expression in cultured cardiomyocytes to exclude any external and enzymatic substrate effects and compared the response between DPP4 knockdown and wild-type cardiomyocytes in response to oxidative stress.Results: H2O2-induced oxidative stress-stimulated intracellular and mitochondrial ROS concentration led to the loss of mitochondrial function, ATP production, and increased Bax and cleaved PARP expression, resulting in the loss of cell viability in cardiomyocytes. Oxidative stress induced DPP4 expression. Knocking down DPP4 ameliorated H2O2-induced loss of cell viability by preserving mitochondrial bioenergy, reducing intracellular ROS production, alleviating apoptosis-associated protein expression. Knocking down DPP4 increased its capability against oxidative stress by enhancing Nrf2 and PGC-1α signaling, which is associated with preserving mitochondrial function.Conclusions: DPP4 is a mediator of oxidative stress. Knocking down DPP4 without any external substrate mediators increased the capability of cardiomyocytes against oxidative stress, which indicated that DPP4 mediated more than the enzymatic-dependent pathway.


2015 ◽  
Vol 37 (4) ◽  
pp. 1431-1441 ◽  
Author(s):  
Qing Song ◽  
Wen-Li Gou ◽  
Rong Zhang

Background/Aims: Oxidative stress-induced cell damage is involved in many neurological diseases. FAM3A is the first member of family with sequence similarity 3 (FAM3) gene family and its biological function remains largely unknown. Methods: This study aimed to determine its role in hydrogen peroxide (H2O2) induced injury in neuronal HT22 cells. The protective effects were measured by cell viability, lactate dehydrogenase (LDH) release and apoptosis, and oxidative stress was assayed by reactive oxygen species (ROS) generation, ATP synthesis and lipid peroxidation. By using selective inhibitors, the involvement of PI3K/Akt and MEK/ERK pathways were also investigated. Results: The results of fluorescence staining revealed that H2O2 significantly decreased the expression of FAM3A protein, which was shown to be subcellularly located in mitochondria. Up-regulation of FAM3A by lentivirus transfection markedly increased cell viability and decreased LDH release after H2O2 treatment. The anti-apoptotic activity of FAM3A was demonstrated by the reduced mitochondrial cytochrome c release, decreased activation of caspase-3 and the results of flow cytometry. Overexpression of FAM3A attenuated intracellular ROS generation and loss of ATP production induced by H2O2, and subsequently inhibited lipid peroxidation. In addition, overexpression of FAM3A significantly increased the activation of Akt and ERK in H2O2 injured HT22 cells. By using Akt and ERK specific inhibitors, we found that inhibition of PI3K/Akt, but not MEK/ERK pathway, partially prevented FAM3A-induced protection against H2O2. Conclusion: These results suggest that FAM3A has protective effects against H2O2-induced oxidative stress by reducing ROS accumulation and apoptosis, and these protective effects are dependent on the activation of PI3K/Akt pathway.


2021 ◽  
Vol 12 (3) ◽  
pp. 1788-1802
Author(s):  
Rajarajan S ◽  
Sivakrishnan S ◽  
Ganesan V

The aim of this study was to see whether an ethanol extract of Eichhornia crassipes flowers and its fractions could protect BRL 3A liver cells from hydrogen peroxide-induced oxidative stress. Eichhornia crassipes powdered flowers were subjected to a hot continuous extraction in a soxhlet extractor using ethanol as the solvent material. The solvent extracts were first tested for in-vitro free radical scavenging and anti-oxidant activity using qualitative and quantitative methods. Benzene, chloroform, and n-butanol were used to fractionate the ethanol extract. In BRL 3A cell lines, the crude ethanol extract and its fractions were tested for their possible cytoprotective effect against hydrogen peroxide (H2O2) induced oxidative stress. Cell viability, lipid peroxidation by measuring the formation of malondialdehyde, lactate dehydrogenase leakage into culture medium, catalase activity, and the content of reduced glutathione (GSH) in the cells were all tested in biochemical assays to determine the cytoprotective activity. BRL 3A cells were exposed to 2mM H2O2, which decreased cell viability, increased malondialdehyde (MDA) levels, increased lactate dehydrogenase (LDH) leakage, and reduced antioxidant activities. Pretreatment of cultured cells for 30 minutes with crude ethanol extract of Eichhornia crassipes flowers and various solvent fractions at concentrations of 0.01, 0.1, 1, 10, 100 g/ml attenuated oxidative injury in a dose-dependent manner until H2O2 exposure. The crude ethanol extract of Eichhornia crassipes flowers was found to have a strong cytoprotective impact, raising cell viability while decreasing lipid peroxidation and LDH leakage. In the cells pre-treated with ethanol extract of Eichhornia crassipes flowers, there was a further increase in catalase and a decrease in glutathione activity. These results indicate that an ethanol extract of Eichhornia crassipes flowers has potent cytoprotective properties against reactive oxygen species-induced oxidative injury.


Author(s):  
S. Rajarajan ◽  
S. Sivakrishnan ◽  
V. Ganesan

The aim of this study was to investigate the cytoprotective effect of ethanol extract of Eichhornia crassipes flowersand its fractions against hydrogen peroxide induced oxidative stress in BRL 3A liver cells. Powdered flowers of Eichhornia crassipeswere subjected to hot continuous extraction in soxhlet extractor using ethanol as solvent material. Initially, the solvent extracts were subjected to qualitative, quantitative analysis and assessed for in-vitro free radical scavenging activity and anti-oxidant activity. The ethanol extract was fractionated using benzene, chloroform and n-butanol. The crude ethanol extract and its fractions were evaluated for its potential cytoprotective effect against hydrogen peroxide (H2O2) induced oxidative stress in BRL 3A cell lines.Biochemical assays were carried out to determine the cytoprotective activity, including cell viability, lipid peroxidation by determining the formation of malondialdehyde, lactate dehydrogenase leakage into culture medium, the catalase activity and the content of reduced glutathione (GSH) in the cells. Exposure of BRL 3A to 2mM H2O2 reduced the cell viability, increased the malondialdehyde (MDA) level, increased the leakage of lactate dehydrogenase (LDH) and caused reduction in antioxidant activities. Pretreatment of cultured cells with crude ethanol extract of Eichhornia crassipes flowers and different solvent fractions at concentrations 0.01, 0.1, 1, 10, 100 μg/ml for 30 minutes before H2O2 exposure attenuated the oxidative injury in dose-dependent manner. It was observed that crude ethanol extract of Eichhornia crassipes flowers exhibited a strong cytoprotective by increasing cell viability, decreasing lipid peroxidation and LDH leakage. Further increase in catalase and reduced glutathione activity was noted in the cells pre-treated with ethanol extract of Eichhornia crassipes flowers. These findings suggest that ethanol extract of Eichhornia crassipes flowers has a strong cytoprotective activity against oxidative injury caused by reactive oxygen species.


2019 ◽  
Vol 19 (9) ◽  
pp. 688-698 ◽  
Author(s):  
Azam Roohi ◽  
Mahin Nikougoftar ◽  
Hamed Montazeri ◽  
Shadisadat Navabi ◽  
Fazel Shokri ◽  
...  

Background: Oxidative stress and chronic hyperglycemia are two major side effects of type 2 diabetes affecting all cell types including mesenchymal stem cells (MSCs). As a cell therapy choice, understanding the behavior of MSCs will provide crucial information for efficient treatment. Methods: Placental mesenchymal stem cells were treated with various concentrations of glucose, metformin, rapamycin, and hydrogen peroxide to monitor their viability and cell cycle distribution. Cellular viability was examined via the MTT assay. Cell cycle distribution was studied by propidium iodide staining and apoptosis was determined using Annexin Vpropidium iodide staining and flow cytometry. Involvement of potential signaling pathways was evaluated by Western blotting for activation of Akt, P70S6K, and AMPK. Results: The results indicated that high glucose augmented cell viability and reduced metformin toxic potential. However, the hydrogen peroxide and rapamycin toxicities were exacerbated. Conclusion: Our findings suggest that high glucose concentration has a major effect on placental mesenchymal stem cell viability in the presence of rapamycin, metformin and hydrogen peroxide in culture.


2020 ◽  
Vol 01 ◽  
Author(s):  
Ayşe Mine Yılmaz ◽  
Gökhan Biçim ◽  
Kübra Toprak ◽  
Betül Karademir Yılmaz ◽  
Irina Milisav ◽  
...  

Background: Different cellular responses influence the progress of cancer. In this study, we have investigated the effect of hydrogen peroxide and quercetin induced changes on cell viability, apoptosis and oxidative stress in human hepatocellular carcinoma (HepG2) cells. Methods: The effects of hydrogen peroxide and quercetin on cell viability, cell cycle phases and oxidative stress related cellular changes were investigated. Cell viability was assessed by WST-1 assay. Apoptosis rate, cell cycle phase changes and oxidative stress were measured by flow cytometry. Protein expressions of p21, p27, p53, NF-Kβ-p50 and proteasome activity were determined by Western blot and fluorometry, respectively. Results: Hydrogen peroxide and quercetin treatment resulted in decreased cell viability and increased apoptosis in HepG2 cells. Proteasome activity was increased by hydrogen peroxide but decreased by quercetin treatment. Conclusion: Both agents resulted in decreased p53 protein expression and increased cell death by different mechanisms regarding proteostasis and cell cycle phases.


2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Nermin Isik ◽  
Ozlem Derinbay Ekici ◽  
Ceylan Ilhan ◽  
Devran Coskun

 Background: Theileriosis is a tick-borne disease caused by Theileria strains of the protozoan species. Buparvaquone is the mostly preferred drug in the treatment theileriosis, while it is safety in sheep, has not been detailed investigated. It has been hypothesized that buparvaquone may show side effects and these effects may be defined some parameters measured from blood in sheep when it is used at the recommended dose and duration. The aim of this research was to determine the effect of buparvaquone on the blood oxidative status, cardiac, hepatic and renal damage and bone marrow function markers.Materials, Methods & Results: In this study, ten adult (> 2 years) Akkaraman rams were used. Healthy rams were placed in paddocks, provided water ad libitum, and fed with appropriate rations during the experiment. Buparvaquone was ad­ministered at the dose of 2.5 mg/kg (IM) intramuscularly twice at 3-day intervals. Blood samples were obtained before (0. h, Control) and after drug administration at 0.25, 0.5, 1, 2, 3, 4 and 5 days. The blood samples were transferred to gel tubes, and the sera were removed (2000 g, 15 min). During the study, the heart rate, respiratory rate, and body temperature were measured at each sampling time. In addition, the animals were clinically observed. Plasma oxidative status mark­ers (Malondialdehyde, total antioxidant status, catalase, glutathione peroxidase, superoxide dismutase), serum cardiac (Troponin I, creatine kinase-MBmass, lactate dehydrogenase), hepatic (Alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total protein, albumin, globulin) and renal (Creatinine, blood urea nitrogen) damage markers and hemogram values (white blood cell, red blood cell, platelet, hemogram, hematocrit) were measured. Buparvaquone caused statistically significantly (P < 0.05) increases in the troponin I and blood urea nitrogen levels and fluctuations in alkaline phosphatase activity, but there was no any statistically significance difference determined in the other parameters.Discussion: In this study, buparvaquone was administered two times at a dose of 2.5 mg/kg (IM) at 3-day intervals. Al­though the result was not statistically significant (P > 0.05), it was determined that buparvaquone gradually increased the levels of the main oxidative stress marker, MDA, by approximately 2.8 fold. CAT and GPX levels were also found to have decreased by 2.2 fold. Buparvaquone may cause lipid peroxidation by producing free radicals. Some other antiprotozoal drugs may affect the oxidative status and may increase MDA level and decrease SOD level. In this study, MDA, which is an indicator of lipid peroxidation in vivo, was used to partially detect developing lipid peroxidation. Changes in the levels of reduced GPX and CAT enzymes could be attributed to their use in mediating the hydrogen peroxide detoxification mechanisms. The absence of significant changes in the TAS levels in this study suggests that buparvaquone may partially induce oxidative stress by producing hydrogen peroxide, but no significant changes occurred in the oxidative stress level because of the high antioxidant capacity of sheep. In this study, buparvaquone caused a statistically significant increase (P < 0.05) in the level of Tn-I, which is a marker of specific cardiac damage (P < 0.05), whereas there was no statistically (P > 0.05) significant increase in CK-MBmass. Tn-I and CK-MB levels, which are used to define heart damage in humans, have been successfully used to determine heart damage in sheep. In this research study, the statistically significant increases in Tn-I but not CK-MBmass levels could be considered indicative of mild cardiac damage.Keywords: ram, buparvaquone, safety.


RSC Advances ◽  
2021 ◽  
Vol 11 (16) ◽  
pp. 9112-9120
Author(s):  
Jenna L. Gordon ◽  
Kristin J. Hinsen ◽  
Melissa M. Reynolds ◽  
Tyler A. Smith ◽  
Haley O. Tucker ◽  
...  

S-Nitrosoglutathione (GSNO) reduces cell viability, inhibits cell division, and induces cell cycle arrest and apoptosis in neuroblastoma cells.


Author(s):  
Luukkonen Jukka ◽  
Höytö Anne ◽  
Sokka Miiko ◽  
Syväoja Juhani ◽  
Juutilainen Jukka ◽  
...  

AbstractIonizing radiation has been shown to cause induced genomic instability (IGI), which is defined as a persistently increased rate of genomic damage in the progeny of the exposed cells. In this study, IGI was investigated by exposing human SH-SY5Y neuroblastoma cells to hydroxyurea and zeocin, two chemicals mimicking different DNA-damaging effects of ionizing radiation. The aim was to explore whether IGI was associated with persistent mitochondrial dysfunction. Changes to mitochondrial function were assessed by analyzing mitochondrial superoxide production, mitochondrial membrane potential, and mitochondrial activity. The formation of micronuclei was used to determine immediate genetic damage and IGI. Measurements were performed either immediately, 8 days, or 15 days following exposure. Both hydroxyurea and zeocin increased mitochondrial superoxide production and affected mitochondrial activity immediately after exposure, and mitochondrial membrane potential was affected by zeocin, but no persistent changes in mitochondrial function were observed. IGI became manifested 15 days after exposure in hydroxyurea-exposed cells. In conclusion, immediate responses in mitochondrial function did not cause persistent dysfunction of mitochondria, and this dysfunction was not required for IGI in human neuroblastoma cells.


Sign in / Sign up

Export Citation Format

Share Document