scholarly journals Ellagic Acid Prevents Dopamine Neuron Degeneration from Oxidative Stress and Neuroinflammation in MPTP Model of Parkinson’s Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1519
Author(s):  
Mustafa T. Ardah ◽  
Greeshma Bharathan ◽  
Tohru Kitada ◽  
M. Emdadul Haque
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Lipid Peroxidation ◽  
Parkinson's Disease ◽  
Body Weight ◽  
Dopamine Transporter ◽  
Inflammatory Cytokines ◽  
Mptp Administration ◽  
Cox 2 ◽  
Pro Inflammatory Cytokines

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and is characterized by progressive dopaminergic neurodegeneration in the substantia nigra pars compacta area. In the present study, treatment of EA for 1 week at a dose of 10 mg/kg body weight prior to MPTP (25 mg/kg body weight) was carried out. MPTP administration caused oxidative stress, as evidenced by decreased activities of superoxide dismutase and catalase, and the depletion of reduced glutathione with a concomitant rise in the lipid peroxidation product, malondialdehyde. It also significantly increased the pro-inflammatory cytokines and elevated the inflammatory mediators like cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the striatum. Immunohistochemical analysis revealed a loss of dopamine neurons in the SNc area and a decrease in dopamine transporter in the striatum following MPTP administration. However, treatment with EA prior to MPTP injection significantly rescued the dopaminergic neurons and dopamine transporter. EA treatment further restored antioxidant enzymes, prevented the depletion of glutathione and inhibited lipid peroxidation, in addition to the attenuation of pro-inflammatory cytokines. EA also reduced the levels of COX-2 and iNOS. The findings of the present study demonstrate that EA protects against MPTP-induced PD and the observed neuroprotective effects can be attributed to its potent antioxidant and anti-inflammatory properties.

Pro-inflammatory Cytokines and Sudden Death in Parkinson’s Disease: a Missing Piece of the Jigsaw Puzzle

2020 ◽  
Vol 15 (4) ◽  
pp. 570-571
Author(s):  
Fulvio A. Scorza ◽  
Antonio-Carlos G. de Almeida ◽  
Carla A. Scorza ◽  
Ana C. Fiorini ◽  
Josef Finsterer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sudden Death ◽  
Inflammatory Cytokines ◽  
Jigsaw Puzzle ◽  
Pro Inflammatory Cytokines

scholarly journals Titán-dioxid-nanopálcikák tüdőre kifejtett hatásának állatkísérletes vizsgálata szubakut patkánymodellben

2019 ◽  
Vol 160 (2) ◽  
pp. 57-66 ◽  
Author(s):  
Tamara Horváth ◽  
András Papp ◽  
Mónika Kiricsi ◽  
Nóra Igaz ◽  
Vivien Trenka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Electron Microscopy ◽  
Lipid Peroxidation ◽  
Lymph Nodes ◽  
Inflammatory Cytokines ◽  
Lung Tissue ◽  
Light And Electron Microscopy ◽  
Biochemical Methods ◽  
Ti Content ◽  
Pro Inflammatory Cytokines

Abstract: Introduction: The development of nanotechnology increases the risk of occupational and population-level exposure to nanoparticles nowadays. However, scientifically based knowledge relating to the toxicity of heavy metal nanoparticles and potential health damage is insufficient. Aim: Investigation of lung tissue damage induced by titanium dioxide (TiO2) nanorods in subacute intratracheal instillation by morphological, chemical and biochemical methods in rat model. Method: General toxicity (changes of body and organ weights), local acute and chronic cellular toxicity (in alveolar spaces and epithelium, in hilar lymph nodes) and oxidative stress were examined using light and electron microscopy, and biochemical methods (reactive oxygen species, lipid peroxidation, expression of pro-inflammatory cytokines). Results: No dose- and time-dependent alteration was found in the body weight of the treated groups; but the mass and Ti content of lungs increased with dose. Light and electron microscopy of the lung tissue verified the presence of nanoparticles, free in the alveolar space and within phagosomes of macrophages not attached to alveolar epithelium. Chronification of local acute alveolitis was supported by dose-dependent increase of macrophage count in the alveolar region, oedema and thickening of interstitium, and increased expression of certain pro-inflammatory cytokines (interleukin-1a, LIX, L-selectin, vascular endothelial growth factor). Oxidative stress and lipid peroxidation increased substantially in the treated rats’ lungs, and correlation was found between Ti content and lipid peroxidation. Insufficiency of the alveolar epithelial and capillary endothelial barrier was indicated by nanoparticle-laden phagocytes in hilar lymph nodes, suggesting nanoparticles reaching systemic circulation and distant organs, inducing systemic acute inflammation. Conclusion: TiO2 nanoparticles, reaching lower airways, may be etiological factors in the causation or aggravation of pulmonary diseases with acute and chronic airways inflammation and/or progressive fibrosis and obstruction (e.g., chronic obstructive pulmonary disease or asthma). Autophagy and damaged immune response (lymphocytic activity) may have here a role. Orv Hetil. 2019; 160(2): 57–66.

scholarly journals Neuroprotective Effects of Thymol, a Dietary Monoterpene Against Dopaminergic Neurodegeneration in Rotenone-Induced Rat Model of Parkinson’s Disease

2019 ◽  
Vol 20 (7) ◽  
pp. 1538 ◽  
Author(s):  
Hayate Javed ◽  
Sheikh Azimullah ◽  
MF Meeran ◽  
Suraiya Ansari ◽  
Shreesh Ojha
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Body Weight ◽  
Therapeutic Potential ◽  
Nigrostriatal System ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Dopaminergic Neurodegeneration

Parkinson’s disease (PD), a multifactorial movement disorder that involves progressive degeneration of the nigrostriatal system affecting the movement ability of the patient. Oxidative stress and neuroinflammation both are shown to be involved in the etiopathogenesis of PD. The aim of this study was to evaluate the therapeutic potential of thymol, a dietary monoterpene phenol in rotenone (ROT)-induced neurodegeneration in rats that precisely mimics PD in humans. Male Wistar rats were injected ROT at a dose of 2.5 mg/kg body weight for 4 weeks, to induce PD. Thymol was co-administered for 4 weeks at a dose of 50 mg/kg body weight, 30 min prior to ROT injection. The markers of dopaminergic neurodegeneration, oxidative stress and inflammation were estimated using biochemical assays, enzyme-linked immunosorbent assay, western blotting and immunocytochemistry. ROT challenge increased the oxidative stress markers, inflammatory enzymes and cytokines as well as caused significant damage to nigrostriatal dopaminergic system of the brain. Thymol treatment in ROT challenged rats appears to significantly attenuate dopaminergic neuronal loss, oxidative stress and inflammation. The present study showed protective effects of thymol in ROT-induced neurotoxicity and neurodegeneration mediated by preservation of endogenous antioxidant defense networks and attenuation of inflammatory mediators including cytokines and enzymes.

scholarly journals Effects of carvacrol and physical exercise on motor and memory impairments associated with Parkinson’s disease

2019 ◽  
Vol 77 (7) ◽  
pp. 493-500 ◽  
Author(s):  
Leila HAMZEHLOEI ◽  
Mohammad Ebrahim REZVANI ◽  
Ziba RAJAEI
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Lipid Peroxidation ◽  
Parkinson's Disease ◽  
Treadmill Exercise ◽  
Memory Deficit ◽  
Rotational Behavior ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
And Oxidative Stress

ABSTRACT The present study was undertaken to investigate the effects of carvacrol and treadmill exercise on memory deficit, rotational behavior and oxidative stress biomarkers in a 6-OHDA-lesioned rat model of Parkinson’s disease. Wistar rats were treated with carvacrol at a dose of 25 mg/kg and/or ran on a treadmill for a week. Then, 6-OHDA was microinjected into the medial forebrain bundle and treatments continued for six more weeks. Aversive memory, rotational behavior and oxidative stress biomarkers were assessed at the end of week six. The 6-OHDA-lesioned group showed a significant increase in rotational behavior and a decrease in step-through latency in the passive avoidance test compared with the sham group. These behaviors were accompanied by increased lipid peroxidation levels and decreased total thiol concentration in the striatum and/or hippocampus of the hemiparkinsonian rats. Moreover, treatment with carvacrol and exercise reduced rotational behavior and improved aversive memory deficit, which was accompanied by decreased lipid peroxidation levels and increased total thiol concentration in the striatum and/or hippocampus. In conclusion, treatment with carvacrol and treadmill exercise ameliorated motor and memory deficits by modulating oxidative stress in the striatum and hippocampus of hemiparkinsonian rats. Therefore, the combination of carvacrol and treadmill exercise could be an effective therapeutic tool for treatment of neurobehavioral deficits in Parkinson’s disease patients.

Polydatin reduces cardiotoxicity of tyrosine kinase inhibitor sunitinib by decreasing pro-oxidative stress, pro-inflammatory cytokines and NLRP3 inflammasome expression.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15065-e15065
Author(s):  
Massimiliano Berretta ◽  
Vincenzo Quagliariello ◽  
Simona Buccolo ◽  
Martina Iovine ◽  
Michelino De Laurentiis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Growth Factors ◽  
Inflammatory Cytokines ◽  
Transcriptional Activation ◽  
Nlrp3 Inflammasome ◽  
Fetal Cardiomyocytes ◽  
Cardioprotective Effects ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

e15065 Background: : Polydatin has anticancer and anti-inflammatory properties, however no studies investigated on its putative cardioprotective effects against anticancer therapies. Sunitinib, a recently-approved, multi-targeted tyrosine kinases inhibitor, prolongs survival in patients with metastatic renal cell carcinoma and gastrointestinal stromal tumors, however a dose related cardiotoxicity was well described. We investigated on the reduction of cytokines and growth factors of polydatin resulting in putative cardioprotective effects. Methods: Human fetal cardiomyocytes were untreated (control) or treated for 48 h with polydatin (50,100,200 and 400 µM) or sunitinib (5,10,25 and 50 µM) alone or combined to polydatin. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). Results: Exposure of adult cardiomyocytes to polydatin combined to plasma-relevant concentrations of sunitinib reduces significantly intracellular reactive oxygen species, lipid peroxidation and cytochrome c release from mitochondria leading to a reduction in cell death compared to cells exposed to sunitinib alone. Polydatin reduces expression of pro-inflammatory cytokines and growth factors involved in myocardial damages and down-regulates the signaling pathway of NLRP3 inflammasome and NF-κB, increasing cellular resistance to sunitinib-mediated damages. Conclusions: Data of the present study, although in vitro, indicate that polydatin, besides reducing oxidative stress, has cardioprotective and anti-inflammatory properties, thus indicating one the mechanism(s) by which this metabolite of resveratrol might decrease sunitinib-mediated cardiotoxicity.

scholarly journals Deletion ofHerpud1Enhances Heme Oxygenase-1 Expression in a Mouse Model of Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Thuong Manh Le ◽  
Koji Hashida ◽  
Hieu Minh Ta ◽  
Mika Takarada-Iemata ◽  
Koichi Kokame ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Heme Oxygenase ◽  
Active Form ◽  
Heme Oxygenase 1 ◽  
Protein Levels ◽  
The Status ◽  
Mptp Administration

Herp is an endoplasmic reticulum- (ER-) resident membrane protein that plays a role in ER-associated degradation. We studied the expression of Herp and its effect on neurodegeneration in a mouse model of Parkinson’s disease (PD), in which both the oxidative stress and the ER stress are evoked. Eight hours after administering a PD-related neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to mice, the expression of Herp increased at both the mRNA and the protein levels. Experiments usingHerpud1+/+andHerpud1−/−mice revealed that the status of acute degeneration of nigrostriatal neurons and reactive astrogliosis was comparable between two genotypes after MPTP injection. However, the expression of a potent antioxidant, heme oxygenase-1 (HO-1), was detected to a higher degree in the astrocytes ofHerpud1−/−mice than in the astrocytes ofHerpud1+/+mice 24 h after MPTP administration. Further experiments using cultured astrocytes revealed that the stress response against MPP+, an active form of MPTP, and hydrogen peroxide, both of which cause oxidative stress, was comparable between the two genotypes. These results suggest that deletion ofHerpud1may cause a slightly higher level of initial damage in the nigrastrial neurons after MPTP administration but is compensated for by higher induction of antioxidants such as HO-1 in astrocytes.

scholarly journals Downregulation of long non-coding RNA SNHG7 protects against inflammation and apoptosis in Parkinson's disease model by targeting miR-425-5p/TRAF5/NF-κB axis

2020 ◽  
Author(s):  
Shan Yu ◽  
Xueshibojie Liu ◽  
Duo Yu ◽  
Changyong E ◽  
Jinghui Yang
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Western Blot ◽  
Inflammatory Cytokines ◽  
Neuronal Apoptosis ◽  
Rt Pcr ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
And Oxidative Stress

Abstract Background Accumulated evidence has established that long non-coding RNA (lncRNA) is involved in the progress of Parkinson's disease (PD). SNHG7, a novel lncRNA, has been found to play a key role in tumorigenesis. However, the SNHG7 expression and its functional effects on PD remain uncharted. Methods RT-PCR was used to detect the expression of SNHG7, miR-425-5p and inflammatory cytokines in the plasma of PD patients and the healthy controls. Rotenone (Rot) was adopted to construct PD models in SD rats and SH-SY5Y cells, respectively. Gain- and loss- of functions of SNHG7 or miR-425-5p were conducted. The expression levels of Caspase3, tyrosine hydroxylase (TH), Iba1 in SD rat striatum was measured via immunohistochemistry and Western blot. Additionally, the expressions of inflammatory cytokines (IL-1β, IL-6, TNF-α) and oxidative stress factors (MDA, SOD, GSH-PX) in the brain tissues were examined using RT-PCR and ELISA. Moreover, the protein levels of TRAF5, I-κB, NF-κB, HO-1, Nrf2 were detected via Western blot. Bioinformatics was applied to predict the targeting relationship between SNHG7, miR-425-5p and TRAF5. Dual luciferase activity assay and RNA immunoprecipitation (RIP) assays were carried out to verify their interactions. Results SNHG7 was found up-regulated in PD patients while miR-425-5p expression was down-regulated (compared to healthy donors). Meanwhile, SNHG7 level was positively correlated with the level of inflammatory cytokines in PD patients. Functional experiments confirmed that SNHG7 downregulation or miR-425-5p overexpression attenuated neuronal apoptosis in the Rot-mediated PD model, TH-positive cell loss and microglia activation by mitigating inflammation and oxidative stress. Mechanistically, SNHG7 served as a competitive endogenous RNA (ceRNA) by sponging miR-425-5p and promoted TRAF5 mediated inflammation and oxidative stress. Conclusion Inhibition of SNHG7 ameliorated neuronal apoptosis in PD through relieving miR-425-5p/TRAF5/NF-κB signaling pathway modulated inflammation and oxidative stress.

Neuroprotective effect of agmatine (decarboxylated l-arginine) against oxidative stress and neuroinflammation in rotenone model of Parkinson’s disease

2018 ◽  
Vol 38 (2) ◽  
pp. 173-184 ◽  
Author(s):  
EK El-Sayed ◽  
AAE Ahmed ◽  
EM El Morsy ◽  
S Nofal
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Body Weight ◽  
Neuroprotective Effect ◽  
Substantia Nigra Pars Compacta ◽  
Sprague Dawley ◽  
Necrosis Factor Alpha ◽  
Age Related ◽  
Sprague Dawley Rats

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease after Alzheimer’s disease, characterized by loss of dopaminergic neurons in substantia nigra pars compacta, accompanied by motor and nonmotor symptoms. The neuropathological hallmarks of PD are well reported, but the etiology of the disease is still undefined; several studies assume that oxidative stress, mitochondrial defects, and neuroinflammation play vital roles in the progress of the disease. The current study was established to investigate the neuroprotective effect of agmatine on a rotenone (ROT)-induced experimental model of PD. Adult male Sprague Dawley rats were subcutaneously injected with ROT at a dose of 2 mg/kg body weight for 35 days. Agmatine was injected intraperitoneally at 50 and 100 mg/kg body weight, 1 h prior to ROT administration. ROT-treated rats that received agmatine showed better performance on beam walking and an elevated number of rears within the cylinder test. In addition, agmatine reduced midbrain malondialdehyde as an indication of lipid peroxidation, pro-inflammatory cytokines including tumor necrosis factor alpha and interleukin-1β, and glial fibrillary acidic protein. Moreover, agmatine was responsible for preventing loss of tyrosine hydroxylase-positive neurons. In conclusion, our study showed that agmatine possesses a dose-dependent neuroprotective effect through its antioxidant and anti-inflammatory activities. These findings need further clinical investigations of agmatine as a promising neuroprotective agent for the future treatment of PD.

scholarly journals Genetic Defects and Pro-inflammatory Cytokines in Parkinson's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Albert Frank Magnusen ◽  
Shelby Loraine Hatton ◽  
Reena Rani ◽  
Manoj Kumar Pandey
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Cytokines ◽  
Brain Inflammation ◽  
Microglial Cells ◽  
Substantia Nigra Pars Compacta ◽  
Genetic Defects ◽  
Motor Symptoms ◽  
Cytokines And Chemokines ◽  
Pro Inflammatory Cytokines

Parkinson's disease (PD) is a movement disorder attributed to the loss of dopaminergic (DA) neurons mainly in the substantia nigra pars compacta. Motor symptoms include resting tremor, rigidity, and bradykinesias, while non-motor symptoms include autonomic dysfunction, anxiety, and sleeping problems. Genetic mutations in a number of genes (e.g., LRRK2, GBA, SNCA, PARK2, PARK6, and PARK7) and the resultant abnormal activation of microglial cells are assumed to be the main reasons for the loss of DA neurons in PD with genetic causes. Additionally, immune cell infiltration and their participation in major histocompatibility complex I (MHCI) and/or MHCII-mediated processing and presentation of cytosolic or mitochondrial antigens activate the microglial cells and cause the massive generation of pro-inflammatory cytokines and chemokines, which are all critical for the propagation of brain inflammation and the neurodegeneration in PD with genetic and idiopathic causes. Despite knowing the involvement of several of such immune devices that trigger neuroinflammation and neurodegeneration in PD, the exact disease mechanism or the innovative biomarker that could detect disease severity in PD linked to LRRK2, GBA, SNCA, PARK2, PARK6, and PARK7 defects is largely unknown. The current review has explored data from genetics, immunology, and in vivo and ex vivo functional studies that demonstrate that certain genetic defects might contribute to microglial cell activation and massive generation of a number of pro-inflammatory cytokines and chemokines, which ultimately drive the brain inflammation and lead to neurodegeneration in PD. Understanding the detailed involvement of a variety of immune mediators, their source, and the target could provide a better understanding of the disease process. This information might be helpful in clinical diagnosis, monitoring of disease progression, and early identification of affected individuals.

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