scholarly journals Genistein reduced the neural apoptosis in the brain of ovariectomised rats by modulating mitochondrial oxidative stress

2010 ◽  
Vol 104 (9) ◽  
pp. 1297-1303 ◽  
Author(s):  
Yan-Hong Huang ◽  
Qing-Hong Zhang
Keyword(s):  
Oxidative Stress ◽  
Learning And Memory ◽  
Caspase 3 ◽  
Visual Learning ◽  
Morris Water Maze Test ◽  
High Dose ◽  
Dependent Manner ◽  
Ovx Rats ◽  
Neural Apoptosis ◽  
The Brain

The present study was undertaken to investigate the antioxidant effect of chronic ingestion of genistein (Gen) against neural death in the brain of ovariectomised (Ovx) rats. The rats were randomly divided into five groups, i.e. sham-operated (sham), Ovx-only, Ovx with 17β-oestradiol, Ovx with low (15 mg/kg) and high (30 mg/kg) doses of Gen (Gen-L and Gen-H), and were orally administered daily with drugs or vehicle for 6 weeks. The learning and memory abilities were measured by Morris water maze test. Oxidative damages in the brain were evaluated by the level of superoxide dismutase (SOD), malondialdehyde (MDA) and monoamine oxidase (MAO) activities. Neural apoptosis was shown by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and caspase-3 activity. In the visual learning and memory test, there were no significant differences among the population means of the five groups. While in the probe trial test, the Gen-L group instead of the Gen-H group exhibited reduced escape latency and increased memory frequency than the Ovx group. Although both doses of Gen could reduce acetylcholinesterase activity, only a low dose of Gen could diminish MDA activity significantly in frontal cortex and enhance SOD content in the hippocampus. In contrast, MAO content was decreased in the cortex by either dose of Gen, while in the hippocampus, only a high dose of Gen appeared to be effective. Interestingly, Gen at both the doses could attenuate the increased number of TUNEL-positive neurons and caspase-3 activity in Ovx rats. These results suggest that Gen confers protection against Ovx-induced neurodegeneration by attenuating oxidative stress, lipid peroxidation and the mitochondria-mediated apoptotic pathway in a region- and dose-dependent manner.

scholarly journals The protection of LingqiHuangban Granule on human retinal endothelial cells against oxidative stress-induced injury by network pharmacology

2020 ◽  
Author(s):  
Zhenzhen Zhang ◽  
Chuandi Zhou ◽  
Deji Draga ◽  
lhamo Thashi ◽  
Zhi Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Caspase 3 ◽  
Network Pharmacology ◽  
High Dose ◽  
Dependent Manner ◽  
Retinal Endothelial Cells ◽  
Holistic Treatment ◽  
Protein Protein Interaction

Abstract Background: LingqiHuangban Granule(LQHBG) is a famous traditional Chinese medicine formula used to manage retinal diseases, as an effective holistic treatment through warming Yang to exert tonifying effects on kidney and invigorating spleen to remove dampness to nourish essence of effect. The study examined protection of LQHBG on oxidative stress-induced injury in human retinal endothelial cells(HRECs) in vitro, determined the potential molecular targets of LQHBG using network pharmacology.Methods: The potential targets of active ingredients in LQHBG were predicted using pharmmapper. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out using Molecule Annotation System. The protein-protein interaction networks were constructed using Cytoscape. LQHBG was administered to rabbits to prepare medicated serum. The apoptosis of HRECs was evaluated by TUNEL and Flow Cytometry(FCM). MDA, SOD, LDH, GSH-Px, and T-AOC were detected. The mRNA expressions of Nrf2, NF-κB and HO-1 were detected, protein expression levels of Nrf2, Bcl-2, NF-κB, HO-1 and caspase-3 were analyzed.Results: TUNEL demonstrated the numbers of apoptotic cells in low-and high-dose LQHBG groups was obviously less than model group(P<0.05). FCM analysis revealed apoptotic rates of HRECs in low-and high-dose LQHBG groups were obviously reduced in a dose-dependent manner(P<0.05). The potential mechanism of LQHBG was the NF-κB pathway identified using PharmMapper. LQHBG significantly decreased MDA, LDH levels and enhanced SOD, GSH-Px and T-AOC generation. LQHBG inhibited upregulation of NF-κB, caspase-3 and enhanced Bcl-2, Nrf2, and HO-1 expression.Conclusion: LQHBG protected HRECs against oxidative-stress via suppression of apoptosis and elevation of antioxidant ability, which may involve activation of Nrf2/ARE/HO-1 pathway and inhibition of NF-κB pathway.

Sufentanil Affects High Glucose-Induced Oxidative Stress in and Apoptosis of Cardiomyocytes by Regulation of miR-142-3p Expression

2021 ◽  
Vol 11 (3) ◽  
pp. 466-470
Author(s):  
Zhiyong Liu ◽  
Cuiqing Ding ◽  
Changqing Yao ◽  
Jinhui Chen
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Sod Activity ◽  
Apoptosis Rate ◽  
Mda Content

To explore the effects and molecular mechanisms of sufentanil on high glucose-induced oxidative stress in and apoptosis of cardiomyocytes, cardiomyocytes H9c2 cells were classified into groups based on different treatments as high-glucose (HG), HG with low, medium, or high-dose sufentanil, HG with high-dose sufentanil and anti-miR-NC, HG with high-dose sufentanil and anti-miR-142-3p, and control. The cells’ superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected using respective kits. The apoptosis rate in each group was detected by flow cytometry. The expressions of cleaved caspase-3 and pro-caspase3 were determined using western blotting. The expression of miR-142-3p in cardiomyocytes was detected using real-time fluorescent quantitative PCR. Compared with the control group, the HG group had decreased SOD activity, pro-caspase-3 expression, and miR-142-3p expression and increased MDA content, apoptosis, and cleaved caspase-3 expression (P < 0.05). Compared with the HG group, the SOD activity and pro-caspase-3 expression increased and the MDA content, apoptosis rate, and cleaved caspase-3 expression decreased in HG cells treated with low, medium, or high-dose sufentanil. The expression of miR-142-3p was increased in a dose-dependent manner (P < 0.05). The interference of miR-142-3p reversed the effect of sufentanil on high glucose-induced oxidative stress in and apoptosis of cardiomyocytes. Sufentanil may inhibit high glucose-induced oxidative stress in and apoptosis of cardiomyocytes by upregulating miR-142-3p expression.

Allium cepa fraction attenuates STZ-induced dementia via cholinesterase inhibition and amelioration of oxidative stress in mice

2020 ◽  
Vol 31 (3) ◽  
Author(s):  
Ravinder Kaur ◽  
Kudrat Randhawa ◽  
Sanimardeep Kaur ◽  
Richa Shri
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Allium Cepa ◽  
Morris Water Maze Test ◽  
Cholinesterase Inhibition ◽  
Significant Activity ◽  
Dependent Manner ◽  
Model Of Alzheimer’S Disease ◽  
The Brain

AbstractBackgroundAn earlier study demonstrated significant antioxidant and anticholinesterase activities of hydromethanol extract (HME) of Allium cepa. The aim of the study was to investigate the component responsible for these activities followed by an in vivo study.MethodsIn vitro antioxidant and anticholinesterase activities of standardized ethylacetate fraction (EAF) of HME were assessed. Bioactivity-guided fractionation showed that, as compared with its subfractions, EAF had most significant activity in 2,2-diphenyl-1-picrylhydrazyl and Ellman assays. Thus, EAF was further examined using a streptozotocin (STZ)-induced model of Alzheimer’s disease in mice. STZ was injected intracerebroventricularly on days 1 and 3 (3 mg/kg) in mice. EAF was thereafter administered (42, 84, and 168 mg/kg b.w./day p.o.) from days 9 to 22. The Morris water maze test was used to evaluate learning and memory in mice. Acetylcholinesterase (AChE) activity and oxidative stress markers were assessed in the brain homogenates of mice. Additionally, histopathological studies were performed to observe effects in the brain at the cellular level. EAF was standardized based on quercetin and quercetin 4′-O-glucoside content using a validated thin layer chromatography densitometric method.ResultsSTZ produced significant (p < 0.05) memory impairment along with oxidative stress and a cholinergic deficit in mice. EAF treatment ameliorated STZ-induced behavioral deficits and biochemical alterations in mice in a significant and dose-dependent manner.ConclusionsOur results show that EAF is efficacious in improving memory and learning via AChE inhibition and antioxidant activity in the mice brain. Thus, AC could be explored further to find out a lead candidate for Alzheimer’s disease.

Dendrobium officinalis Flower Improves Learning and Reduces Memory Impairment by Mediating Antioxidant Effect and Balancing the Release of Neurotransmitters in Senescent Rats

2020 ◽  
Vol 23 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Lin-Zi Li ◽  
Shan-Shan Lei ◽  
Bo Li ◽  
Fu-Chen Zhou ◽  
Ye-Hui Chen ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Brain Aging ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Histopathological Analysis ◽  
Hippocampal Damage ◽  
Common Belief ◽  
Mao B ◽  
Positive Effects ◽  
The Brain

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.

Combination of Histone Deacetylase Inhibitor with Cu(II) 5,5- diethylbarbiturate Complex Induces Apoptosis in Breast Cancer Stem Cells: A Promising Novel Approach

2020 ◽  
Vol 21 ◽  
Author(s):  
Merve Erkisa ◽  
Nazlihan Aztopal ◽  
Elif Erturk ◽  
Engin Ulukaya ◽  
Veysel T. Yilmaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Histone Deacetylases ◽  
Caspase 3 ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Tumor Formation ◽  
Dependent Manner

Background: Cancer stem cells (CSC) are subpopulation within the tumor that acts a part in the initiation, progression, recurrence, resistance to drugs and metastasis of cancer. It is well known that epigenetic changes lead to tumor formation in cancer stem cells and show drug resistance. Epigenetic modulators and /or their combination with different agents have been used in cancer therapy. Objective: In our study we scope out the effects of combination of a histone deacetylases inhibitor, valproic acid (VPA), and Cu(II) complex [Cu(barb-κN)(barb-κ2N,O)(phen-κN,N’)]·H2O] on cytotoxicity/apoptosis in a stem-cell enriched population (MCF-7s) obtained from parental breast cancer cell line (MCF-7). Methods: Viability of the cells was measured by the ATP assay. Apoptosis was elucidated via the assessment of caspase-cleaved cytokeratin 18 (M30 ELISA) and a group of flow cytometry analysis (caspase 3/7 activity, phosphatidylserine translocation by annexin V-FITC assay, DNA damage and oxidative stress) and 2ˈ,7ˈ–dichlorofluorescein diacetate staining. Results: The VPA combined with Cu(II) complex showed anti proliferative activity on MCF-7s cells in a dose- and time-dependently. Treatment with combination of 2.5 mM VPA and 3.12 μM Cu(II) complex induces oxidative stress in a time-dependent manner, as well as apoptosis that is evidenced by the increase in caspase 3/7 activity, positive annexin-V-FITC, and increase in M30 levels. Conclusion: The results suggest that the combination therapy induces apoptosis following increased oxidative stress, thereby making it a possible promising therapeutic strategy that further analysis is required.

scholarly journals Concentration-Dependent Antioxidant/Pro-Oxidant Activity of Ascorbic Acid in Chickens

2012 ◽  
Vol 66 (6) ◽  
pp. 256-260
Author(s):  
Nadežda Berzina ◽  
Jurijs Markovs ◽  
Mirdza Apsīte ◽  
Svetlana Vasiļjeva ◽  
Galina Smirnova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ascorbic Acid ◽  
Cadmium Concentration ◽  
Dehydroascorbic Acid ◽  
Cadmium Accumulation ◽  
Suppressive Effect ◽  
High Dose ◽  
Dependent Manner ◽  
Treatment Groups ◽  
Liver And Kidney

The effects of ascorbic acid supplementation on biomarkers of oxidative stress, cadmium accumulation in organs, immune system activity and kidney function in chickens were investigated. The treatment groups of chickens were fed either plain diet or diet supplemented with ascorbic acid at 100, 500, 1000 and 2000 mg/kg for four weeks. Liver and kidney tissues were assayed for cadmium concentration, and the hepatic levels of ascorbic acid and dehydroascorbic acid (DHAA; the oxidised form), malondialdehyde, glutathione, activity of glutathione peroxidase, blood serum uric acid, creatinine, lysozyme and circulating immune complexes were measured. Supplementation with a high dose of ascorbic acid (1000 and 2000 mg/kg in the diet) caused an imbalance between pro-oxidative and antioxidative activities, and induced a suppressive effect on innate immunity. The results suggest that oxidative stress compromises renal function. We observed that ascorbic acid increased cadmium accumulation in a dose-dependent manner.

scholarly journals Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT to Cause Oxidative Damage in the Striatum of Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xinxin Yang ◽  
Haibo Yang ◽  
Fengdi Wu ◽  
Zhipeng Qi ◽  
Jiashuo Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Dependent Manner ◽  
Protein Levels ◽  
Key Factor ◽  
Protein Sulfhydryl ◽  
Mrna And Protein Expression ◽  
The Brain

Excessive manganese (Mn) can accumulate in the striatum of the brain following overexposure. Oxidative stress is a well-recognized mechanism in Mn-induced neurotoxicity. It has been proven that glutathione (GSH) depletion is a key factor in oxidative damage during Mn exposure. However, no study has focused on the dysfunction of GSH synthesis-induced oxidative stress in the brain during Mn exposure. The objective of the present study was to explore the mechanism of Mn disruption of GSH synthesis via EAAC1 and xCT in vitro and in vivo. Primary neurons and astrocytes were cultured and treated with different doses of Mn to observe the state of cells and levels of GSH and reactive oxygen species (ROS) and measure mRNA and protein expression of EAAC1 and xCT. Mice were randomly divided into seven groups, which received saline, 12.5, 25, and 50 mg/kg MnCl2, 500 mg/kg AAH (EAAC1 inhibitor) + 50 mg/kg MnCl2, 75 mg/kg SSZ (xCT inhibitor) + 50 mg/kg MnCl2, and 100 mg/kg NAC (GSH rescuer) + 50 mg/kg MnCl2 once daily for two weeks. Then, levels of EAAC1, xCT, ROS, GSH, malondialdehyde (MDA), protein sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and morphological and ultrastructural features in the striatum of mice were measured. Mn reduced protein levels, mRNA expression, and immunofluorescence intensity of EAAC1 and xCT. Mn also decreased the level of GSH, sulfhydryl, and increased ROS, MDA, 8-OHdG, and carbonyl in a dose-dependent manner. Injury-related pathological and ultrastructure changes in the striatum of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GSH synthesis through inhibition of EAAC1 and xCT to trigger oxidative damage in the striatum.

Soybean Isoflavones Influences Learning and Memory and Caspase-3 Levels in the Hippocampus of Rats after MWM Test

2013 ◽  
Vol 411-414 ◽  
pp. 3178-3180
Author(s):  
Li Hai Jin ◽  
Xing Yu Zhao ◽  
Wei Zhang ◽  
Wei Chen ◽  
Guo Qing Sun ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
Memory Impairment ◽  
Caspase 3 ◽  
Morris Water Maze Test ◽  
Once Daily ◽  
Soybean Isoflavones ◽  
Maze Test ◽  
Intermediate Dose

We assessed the effectiveness and mechanism of action of Soybean Isoflavones on learning and memory and Caspase-3 levels in the hippocampus of rats after Morris water maze (MWM test). Soybean Isoflavones (200,400 or 800 mg/kg/d) were administered by intragavage once daily for 14 consecutive days. The Morris water maze test was used to evaluate the ability of Soybean Isoflavones to increase learning and memory impairment. The levels of Caspase-3 in hippocampus of rats were detected by Westernblot after MWM test. Compared to untreated controls (P<0.01), MWM could be prolonged after Soybean Isoflavones treatment (P<0.05 for="" low="" and="" intermediate="" dose="" groups="" westernblot="" analysis="" showed="" that="" the="" protein="" expression="" of="" caspase-3="" was="" decreased="" in="" different="" concentration="" soybean="" isoflavones="" i="">P<0.05 and="" i="">P<0.01, respectively). The results suggest that Soybean Isoflavones is effective in improving the learning and memory in rats , the mechanism of which may be related Caspase ways.

Abstinence from chronic methylphenidate exposure modifies cannabinoid receptor 1 levels in the brain in a dose-dependent manner

2021 ◽  
Vol 27 ◽  
Author(s):  
Carly Connor ◽  
John Hamilton ◽  
Lisa Robison ◽  
Michael Hadjiargyrou ◽  
David Komatsu ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
High Dose ◽  
Dependent Manner ◽  
Water Control ◽  
Cannabinoid Receptor 1 ◽  
The Brain ◽  
Abstinence Period

Introduction: Methylphenidate (MP) is a widely used psychostimulant prescribed for Attention Deficit Hyperactivity Disorder, and is also used illicitly by healthy individuals. Chronic exposure to MP has been shown to affect physiology, behavior, and neurochemistry. Methods: The present study examined its effect on the endocannabinoid system. Adolescent rats had daily oral access to either water (control), low dose MP (4/10 mg/kg), or high dose MP (30/60 mg/kg). After 13 weeks of exposure, half of the rats in each group were euthanized, however the remaining rats underwent a four-week long abstinence period. Cannabinoid receptor 1 binding (CB1) was measured with in vitro autoradiography using [3H] SR141716A. Results: Rats who underwent a 4-week abstinence period after exposure to chronic HD MP showed increased binding compared to rats with no abstinence period in several cortical and basal ganglia regions of the brain. In contrast to this, rats who underwent a 4-week abstinence period after exposure to chronic LD MP showed lower binding compared to rats with no abstinence period in mainly the basal ganglia regions and in the hindlimb region of the somatosensory cortex. Following 4 weeks of drug abstinence, rats who were previously given HD MP showed higher [ 3H] SR141716A binding than rats given LD MP in many of the cortical and basal ganglia regions examined. These results highlight biphasic effects of MP treatment on cannabinoid receptor levels. Abstinence from HD MP seemed to increase CB1 receptor levels while abstinence from LD MP seemed to decrease CB1 levels. Conclusion: Given the prolific expression of cannabinoid receptors throughout the brain, many types of behaviors may be affected as a result of MP abstinence. Further research will be needed to help identify these behavioral changes.

scholarly journals Nrf2 Ablation Promotes Alzheimer’s Disease-Like Pathology in APP/PS1 Transgenic Mice: The Role of Neuroinflammation and Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Peng Ren ◽  
Jingwei Chen ◽  
Bingxuan Li ◽  
Mengzhou Zhang ◽  
Bei Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Related Factor ◽  
Qrt Pcr

Introduction. Alzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by the accumulation of amyloid-β (Aβ) peptide and hyperphosphorylated tau protein. Accumulating evidence has revealed that the slow progressive deterioration of AD is associated with oxidative stress and chronic inflammation in the brain. Nuclear factor erythroid 2- (NF-E2-) related factor 2 (Nrf2), which acts through the Nrf2/ARE pathway, is a key regulator of the antioxidant and anti-inflammatory response. Although recent data show a link between Nrf2 and AD-related cognitive decline, the mechanism is still unknown. Thus, we explored how Nrf2 protects brain cells against the oxidative stress and inflammation of AD in a mouse model of AD (APP/PS1 transgenic (AT) mice) with genetic removal of Nrf2. Methods. The spatial learning and memory abilities of 12-month-old transgenic mice were evaluated using a Morris water maze test. Hippocampal levels of Nrf2, Aβ, and p-tauS404 and of astrocytes and microglia were determined by immunostaining. Inflammatory cytokines were determined by ELISA and quantitative real-time polymerase chain reaction (qRT-PCR). Oxidative stress was measured by 8-hydroxydeoxyguanosine immunohistochemistry, and the antioxidant response was determined by qRT-PCR. Results. The spatial learning and memory abilities of AT mice were impaired after Nrf2 deletion. Aβ and p-tauS404 accumulation was increased in the hippocampus of AT/Nrf2-KO mice. Astroglial and microglial activation was exacerbated, followed by upregulation of the proinflammatory cytokines IL-1β, IL-6, and TNF-α. Conclusion. Our present results show that Nrf2 deficiency aggravates AD-like pathology in AT mice. This phenotype was associated with increased levels of oxidative and proinflammatory markers, which suggests that the Nrf2 pathway may be a promising therapeutic target for AD.

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