scholarly journals Molecular mechanisms of aluminium ions neurotoxicity in brain cells of fish from various pelagic areas

2017 ◽  
Vol 8 (3) ◽  
pp. 461-466 ◽  
Author(s):  
E. V. Sukharenko ◽  
I. V. Samoylova ◽  
V. S. Nedzvetsky
Keyword(s):  
Oxidative Stress ◽  
Molecular Weight ◽  
Intermediate Filaments ◽  
Aluminum Chloride ◽  
Molecular Mechanisms ◽  
Lepomis Macrochirus ◽  
Fish Brain ◽  
Mature Adult ◽  
Aluminum Ions ◽  
The Brain

Neurotoxic effects of aluminum chloride in higher than usual environment concentration (10 mg/L) were studied in brains of fishes from various pelagic areas, especially in sunfish (Lepomis macrochirus Rafinesque, 1819), roach (Rutilus rutilus Linnaeus, 1758), crucian carp (Carasius carasius Linnaeus, 1758), goby (Neogobius fluviatilis Pallas, 1811). The intensity of oxidative stress and the content of both cytoskeleton protein GFAP and cytosol Ca-binding protein S100β were determined. The differences in oxidative stress data were observed in the liver and brain of fish during 45 days of treatment with aluminum chloride. The data indicated that in the modeling of aluminum intoxication in mature adult fishes the level of oxidative stress was noticeably higher in the brain than in the liver. This index was lower by1.5–2.0 times on average in the liver cells than in the brain. The obtained data evidently demonstrate high sensitivity to aluminum ions in neural tissue cells of fish from various pelagic areas. Chronic intoxication with aluminum ions induced intense astrogliosis in the fish brain. Astrogliosis was determined as result of overexpression of both cytoskeleton and cytosole markers of astrocytes – GFAP and protein S100β (on 75–112% and 67–105% accordingly). Moreover, it was shown that the neurotixic effect of aluminum ions is closely related to metabolism of astroglial intermediate filaments. The results of western blotting showed a considerable increase in the content of the lysis protein products of GFAP with a range of molecular weight from 40–49 kDa. A similar metabolic disturbance was determined for the upregulation protein S100β expression and particularly in the increase in the content of polypeptide fragments of this protein with molecular weight 24–37 kDa. Thus, the obtained results allow one to presume that aluminum ions activate in the fish brain intracellular proteases which have a capacity to destroy the proteins of intermediate filaments. The data presented display the pronounced neurotoxic effect of mobile forms of aluminum on both expression level and the metabolism of molecular markers of astrocytes GFAP and protein S100β. Aluminum ions induce integrated changes, the more important of which are a significant increase in final LPO products, an increase in antioxidant enzyme activity, a reactivation of glial cells in the brain. Integrated determination of the content and polypeptide fragments of specific astrocyte proteins in fishes brains coupled with oxidative stress data may be used as valid biomarkers of toxic pollutant effects in aquatic environments.

scholarly journals Natural Compounds as Inhibitors of Aβ Peptide Aggregation: Chemical Requirements and Molecular Mechanisms

2020 ◽  
Vol 14 ◽  
Author(s):  
Katiuscia Pagano ◽  
Simona Tomaselli ◽  
Henriette Molinari ◽  
Laura Ragona
Keyword(s):  
Molecular Weight ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Natural Compounds ◽  
Preventive Therapy ◽  
Small Subset ◽  
Aβ Peptide ◽  
Aβ Oligomers ◽  
Chemical Structures ◽  
The Brain

Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, with no cure and preventive therapy. Misfolding and extracellular aggregation of Amyloid-β (Aβ) peptides are recognized as the main cause of AD progression, leading to the formation of toxic Aβ oligomers and to the deposition of β-amyloid plaques in the brain, representing the hallmarks of AD. Given the urgent need to provide alternative therapies, natural products serve as vital resources for novel drugs. In recent years, several natural compounds with different chemical structures, such as polyphenols, alkaloids, terpenes, flavonoids, tannins, saponins and vitamins from plants have received attention for their role against the neurodegenerative pathological processes. However, only for a small subset of them experimental evidences are provided on their mechanism of action. This review focuses on those natural compounds shown to interfere with Aβ aggregation by direct interaction with Aβ peptide and whose inhibitory mechanism has been investigated by means of biophysical and structural biology experimental approaches. In few cases, the combination of approaches offering a macroscopic characterization of the oligomers, such as TEM, AFM, fluorescence, together with high-resolution methods could shed light on the complex mechanism of inhibition. In particular, solution NMR spectroscopy, through peptide-based and ligand-based observation, was successfully employed to investigate the interactions of the natural compounds with both soluble NMR-visible (monomer and low molecular weight oligomers) and NMR-invisible (high molecular weight oligomers and protofibrils) species. The molecular determinants of the interaction of promising natural compounds are here compared to infer the chemical requirements of the inhibitors and the common mechanisms of inhibition. Most of the data converge to indicate that the Aβ regions relevant to perturb the aggregation cascade and regulate the toxicity of the stabilized oligomers, are the N-term and β1 region. The ability of the natural aggregation inhibitors to cross the brain blood barrier, together with the tactics to improve their low bioavailability are discussed. The analysis of the data ensemble can provide a rationale for the selection of natural compounds as molecular scaffolds for the design of new therapeutic strategies against the progression of early and late stages of AD.

scholarly journals Methamphetamine-Triggered Neurotoxicity in Human Dorsolateral Prefrontal Cortex

2021 ◽  
Vol 10 ◽  
pp. 2016
Author(s):  
Ali Zare ◽  
Alireza Ghanbari ◽  
Mohammad Javad Hoseinpour ◽  
Mahdi Eskandarian Boroujeni ◽  
Alimohammad Alimohammadi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Metabolic Activation ◽  
Neural Cells ◽  
Dorsolateral Prefrontal ◽  
The Central Nervous System ◽  
The Brain

Background: Methamphetamine (MA), is an extremely addictive stimulant that adversely affects the central nervous system. Accumulating evidence indicates that molecular mechanisms such as oxidative stress, apoptosis, and autophagy are involved in the toxicity of MA. Considering experimental animal studies exhibiting MA-induced neurotoxicity, the relevance of these findings needs to be evidently elucidated in human MA users. It is generally assumed that multiple chemical substances released in the brain following MA-induced metabolic activation are primary factors underlying damage of neural cells. Hence, this study aimed to investigate the role of autophagy and apoptosis as well as oxidative stress in the brain of postmortem MA-induced toxicity. Materials and Methods: In this study, we determine the gene expression of autophagy and apoptosis, including BECN1, MAP1ALC3, CASP8, TP53, and BAX genes in ten healthy controls and ten chronic users of MA postmortem dorsolateral prefrontal cortex (DLPFC) by real-time polymerase chain reaction. Also, we applied immunohistochemistry in formalin-fixed and paraffin-embedded human brain samples to analyze brain-derived neurotrophic factor (BDNF). Also, spectrophotometry was performed to measure glutathione (GSH) content. Results: The expression level of apoptotic and autophagic genes (BECN1, MAP1ALC3, CASP8, TP53, and BAX) were significantly elevated, while GSH content and BDNF showed substantial reductions in DLPFC of chronic MA users. Discussion: Our data showed that MA addiction provokes transduction pathways, namely apoptosis and autophagy, along with oxidative mechanisms in DLPFC. Also, MA induces multiple functional and structural perturbations in the brain, determining its toxicity and possibly contributing to neurotoxicity. [GMJ.2021;10:e2016]

scholarly journals The Antioxidative Action of ZTP by Increasing Nrf2/ARE Signal Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Liang Yang ◽  
Bing Xu ◽  
Chunxu Yuan ◽  
Zhi Dai ◽  
Yong Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Circulation ◽  
Molecular Mechanisms ◽  
Immune Reaction ◽  
Brain Diseases ◽  
Stress Injury ◽  
Cell Death Gene ◽  
Antioxidant Stress ◽  
Antioxidative Action ◽  
The Brain

So far, more than 25,000 brain diseases have been shown to be related to oxidative stress. Excessive free radicals and reactive oxygen species (ROS) can attack cells resulting in dysfunctional proteins, lipids, and nucleic acid, finally leading to imbalance of energy metabolism, cell death, gene mutation, and immune reaction. Therefore oxidative stress plays an important role in neuronal diseases. As a traditional Chinese medicine, Zhengtian Pill (ZTP) was reported to have the ability to reduce the blood viscosity of migraine model rats, with increased beta-endorphin, serotonin, adrenaline, and dopamine in brain tissue. Moreover ZTP can effectively accelerate blood circulation and attenuate blood coagulation. However, the molecular mechanisms of ZPT are still unclear. Through the behavioral test we found that ZTP can significantly improve depression-like behavior induced by LPS when rat was treated with ZTP (L 0.17 g/kg, M 0.34 g/kg, and H 0.7 g/kg) intraperitoneal injection once a day for 30 consecutive days. And ZTP can resist oxidative stress (>72 h) for a longer time. And ZTP can promote the levels of ATP and SOD and reduce the levels of ROS and MDA in the brain. At the same time, ZTP can have antioxidant stress through increasing the expression level of Nrf2/HO-1/P38. These results show that ZTP may be a potential antioxidant stress drug for variety of diseases associated with oxidative stress injury.

scholarly journals Walnut Protein Hydrolysates Play a Protective Role on Neurotoxicity Induced by d-Galactose and Aluminum Chloride in Mice

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2308 ◽  
Author(s):  
Li Feng ◽  
Xiaojing Wang ◽  
Fei Peng ◽  
Jianqiao Liao ◽  
Yifan Nai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Aluminum Chloride ◽  
Neuroprotective Effect ◽  
Protective Role ◽  
Protein Hydrolysates ◽  
Memory Functions ◽  
Cholinergic Dysfunction ◽  
Meal Protein ◽  
The Brain

In recent years, with an increase in the aging population, neurodegenerative diseases have attracted more and more attention. This study aimed to investigate the potential neuroprotective effect of defatted walnut meal protein hydrolysates (DWMPH) on neurotoxicity induced by d-galactose (d-gal) and aluminum chloride (AlCl3) in mice. The animal models were established by combining treatments with d-gal (200 mg/kg/day, subcutaneously) and AlCl3 (100 mg/kg in drinking water) for 90 days. During the 90 days, 1 g/kg of DWMPH was administrated orally every day. The results indicated that DWMPH treatment alleviated oxidative stress, reversed cholinergic dysfunction, and suppressed the release of proinflammatory cytokines in the brains of d-gal + AlCl3-treated mice, and thus improving the learning and memory functions of these mice, which was closely correlated with the strong antioxidant activity of DWMPH. This finding suggests that DWMPH might be a promising dietary supplement in improving neuronal dysfunctions of the brain.

scholarly journals Diabetes and Alzheimer’s Disease: Might Mitochondrial Dysfunction Help Deciphering the Common Path?

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1257
Author(s):  
Maria Assunta Potenza ◽  
Luca Sgarra ◽  
Vanessa Desantis ◽  
Carmela Nacci ◽  
Monica Montagnani
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Senile Plaques ◽  
Mitochondrial Activity ◽  
Enhanced Production ◽  
The Common ◽  
The Brain

A growing number of clinical and epidemiological studies support the hypothesis of a tight correlation between type 2 diabetes mellitus (T2DM) and the development risk of Alzheimer’s disease (AD). Indeed, the proposed definition of Alzheimer’s disease as type 3 diabetes (T3D) underlines the key role played by deranged insulin signaling to accumulation of aggregated amyloid beta (Aβ) peptides in the senile plaques of the brain. Metabolic disturbances such as hyperglycemia, peripheral hyperinsulinemia, dysregulated lipid metabolism, and chronic inflammation associated with T2DM are responsible for an inefficient transport of insulin to the brain, producing a neuronal insulin resistance that triggers an enhanced production and deposition of Aβ and concomitantly contributes to impairment in the micro-tubule-associated protein Tau, leading to neural degeneration and cognitive decline. Furthermore, the reduced antioxidant capacity observed in T2DM patients, together with the impairment of cerebral glucose metabolism and the decreased performance of mitochondrial activity, suggests the existence of a relationship between oxidative damage, mitochondrial impairment, and cognitive dysfunction that could further reinforce the common pathophysiology of T2DM and AD. In this review, we discuss the molecular mechanisms by which insulin-signaling dysregulation in T2DM can contribute to the pathogenesis and progression of AD, deepening the analysis of complex mechanisms involved in reactive oxygen species (ROS) production under oxidative stress and their possible influence in AD and T2DM. In addition, the role of current therapies as tools for prevention or treatment of damage induced by oxidative stress in T2DM and AD will be debated.

scholarly journals Elucidating the Multi-Targeted Role of Nutraceuticals: A Complementary Therapy to Starve Neurodegenerative Diseases

2021 ◽  
Vol 22 (8) ◽  
pp. 4045
Author(s):  
Tapan Behl ◽  
Gagandeep Kaur ◽  
Aayush Sehgal ◽  
Sukhbir Singh ◽  
Saurabh Bhatia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Financial Burden ◽  
Complementary Therapy ◽  
Therapeutic Interventions ◽  
Multifactorial Diseases ◽  
Mitochondrial Homeostasis ◽  
Attractive Option ◽  
The Brain

The mechanisms underlying multifactorial diseases are always complex and challenging. Neurodegenerative disorders (NDs) are common around the globe, posing a critical healthcare issue and financial burden to the country. However, integrative evidence implies some common shared mechanisms and pathways in NDs, which include mitochondrial dysfunction, neuroinflammation, oxidative stress, intracellular calcium overload, protein aggregates, oxidative stress (OS), and neuronal destruction in specific regions of the brain, owing to multifaceted pathologies. The co-existence of these multiple pathways often limits the advantages of available therapies. The nutraceutical-based approach has opened the doors to target these common multifaceted pathways in a slow and more physiological manner to starve the NDs. Peer-reviewed articles were searched via MEDLINE and PubMed published to date for in-depth research and database collection. Considered to be complementary therapy with current clinical management and common drug therapy, the intake of nutraceuticals is considered safe to target multiple mechanisms of action in NDs. The current review summarizes the popular nutraceuticals showing different effects (anti-inflammatory, antioxidant, neuro-protectant, mitochondrial homeostasis, neurogenesis promotion, and autophagy regulation) on vital molecular mechanisms involved in NDs, which can be considered as complementary therapy to first-line treatment. Moreover, owing to its natural source, lower toxicity, therapeutic interventions, biocompatibility, potential nutritional effects, and presence of various anti-oxidative and neuroprotective constituents, the nutraceuticals serve as an attractive option to tackle NDs.

scholarly journals Indices of the DNA repair system in the brain of fish as a biomarker of inorganic mercury burden

2021 ◽  
Vol 32 (1) ◽  
pp. 9-16
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
R. O. Novitskyi ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Environmental Pollution ◽  
Dose Range ◽  
Inorganic Mercury ◽  
Mercury Chloride ◽  
Repair System ◽  
Fish Brain ◽  
Low Concentrations ◽  
The Brain

Mercury is a widespread heavy metal that causes a stable and prolonged environmental pollution. Low concentrations of inorganic and organic mercury compounds are found in almost all water bodies. The high level of mercury bioaccumulation is a cause of tissue-specific toxicity, including neurotoxicity. Absorbed in nervous tissue mercury can cause brain disorders both in neural and glial cells. The brain of fish is considered one of the most susceptible targets for cytotoxicity of mercury in aquatic ecosystems. Taking into account that different forms of mercury have widespread distribution and exhibit a strong neurotoxic effect, the assessment of mercury cytotoxicity in the brain of fish is relevant and extremely important. Rainbow trout Oncorhynchus mykiss was exposed to mercury chloride in the dose range of 5-20 μg/L for 60 days to study the chronic exposure of low doses. In this paper, we studied the influence of inorganic mercury on oxidative stress, DNA repair proteins – ERCC1 and PARP1 in the trout’s brain. The results obtained have shown that the chronic effect of inorganic mercury causes dose-dependent oxidative stress in the fish brain. In addition, low concentrations of mercury (10 and 20 μg/L) caused a decrease in the content of ERCC1 in the brain of fish. On the contrary, the same doses have caused an increase in PARP1 expression. That is the chronic influence of low concentrations of inorganic mercury has a negative effect in the fish brain. Observed results showed that inorganic mercury has a potential for suppressing DNA repair and, therefore, increases the instability of genome. Thus, ERCC1 and PARP1 can be considered as the sensitive biomarkers of mercury cytotoxicity in the fish brain. A further study of mercury neurotoxicity is needed to find out the hazard of mercury environmental pollution as well as a validation of biomarkers of their impact.

Sulforaphane Reverses the Amyloid-β Oligomers Induced Depressive-Like Behavior

2020 ◽  
Vol 78 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Wei Wang ◽  
Cuibai Wei ◽  
Meina Quan ◽  
Tingting Li ◽  
Jianping Jia
Keyword(s):  
Oxidative Stress ◽  
Memory Impairment ◽  
Molecular Mechanisms ◽  
Psychological Symptoms ◽  
Amyloid Β ◽  
Serotonergic System ◽  
Inflammatory Factors ◽  
The Relationship ◽  
The Brain ◽  
And Oxidative Stress

Background: Depression is one of the most common behavioral and psychological symptoms in people with Alzheimer’s disease (AD). To date, however, the molecular mechanisms underlying the clinical association between depression and AD remained elusive. Objective: Here, we study the relationship between memory impairment and depressive-like behavior in AD animal model, and investigate the potential mechanisms. Methods: Male SD rats were administered amyloid-β oligomers (AβOs) by intracerebroventricular injection, and then the depressive-like behavior, neuroinflammation, oxidative stress, and the serotonergic system were measured in the brain. Sulforaphane (SF), a compound with dual capacities of anti-inflammation and anti-oxidative stress, was injected intraperitoneally to evaluate the therapeutic effect. Results: The results showed that AβOs induced both memory impairment and depressive-like behavior in rats, through the mechanisms of inducing neuroinflammation and oxidative stress, and impairing the serotonergic axis. SF could reduce both inflammatory factors and oxidative stress parameters to protect the serotonergic system and alleviate memory impairment and depressive-like behavior in rats. Conclusion: These results provided insights into the biological mechanisms underlying the clinical link between depressive disorder and AD, and offered new drug options for the treatment of depressive symptoms in dementia.

scholarly journals Original article. Protective effect of resveratrol against neuronal damage through oxidative stress in cerebral hemisphere of aluminum and fluoride treated rats

2016 ◽  
Vol 9 (2) ◽  
pp. 78-82 ◽  
Author(s):  
Chandra Shakar Reddy Nalagoni ◽  
Pratap Reddy Karnati
Keyword(s):  
Oxidative Stress ◽  
Sodium Fluoride ◽  
Aluminum Chloride ◽  
Neuronal Damage ◽  
Protective Effects ◽  
Significant Reversal ◽  
Markers Of Oxidative Stress ◽  
Anti Oxidant ◽  
Hematoxylin And Eosin ◽  
The Brain

Abstract Aluminum has no defined biological function and it is potentially involved in the pathogenesis of neurodegenerative disorders. Furthermore, the presence of fluoride causes more aluminum to accumulate in the brain, resulting in increased neuronal damage. In recent years, resveratrol through its ameliorative effects was found to be a neuroprotectant. This study reports the protective effects of resveratrol on combined aluminum and fluoride induced neuronal damage through oxidative stress in rats. Protective effects of resveratrol (30 mg/kg b.w) on markers of oxidative stress were determined in rats exposed to aluminum chloride (100 mg/kg b.w) along with sodium fluoride (10 mg/kg b.w) for 8 weeks. The results showed a statistically significant (p<0.05) increase in lipid peroxidation (LPx) as well as a significant (p<0.05) decrease in superoxide dismutase and catalase activity. Enlarged cells, neurofibrillary tangles, and vacuolar spaces showing oxidative stress in the cerebral cortex were also observed in hematoxylin and eosin stained sections in aluminum and fluoride treated rats. Administration of resveratrol along with aluminum + fluoride showed significant reversal of oxidative stress and neuronal damage in rats. Thus resveratrol potentially acts as a neuroprotectant against aluminum chloride + sodium fluoride induced neuronal damage through its anti-oxidant efficacy.

scholarly journals Influence of cadmium contamination on brain glial cells: consequences and bioindication possibilities

2020 ◽  
Vol 49 ◽  
pp. 67-83
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
A. M. Hahut ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Glial Cells ◽  
Functional Activity ◽  
Molecular Mechanisms ◽  
Glucose Utilization ◽  
Animal Health ◽  
Toxic Effects ◽  
Low Doses ◽  
Cellular Models ◽  
The Brain

Cadmium (Cd) is a heavy metal that currently presents in almost all components of the environment. Cd is a ubiquitous pollutant that is constantly entering the environment from industry and agriculture, mining, forest fires and many more sources. Some occupational diseases have aftereffects associated with Cd cytotoxicity. Despite long-term studies of the toxic effects of Cd, its cytotoxicity of low doses and the chronic effects on the nerve tissue cells remain undiscovered. The results of determining the Cd neurotoxicity indicate a disturbance of the permeability of the blood-brain barrier, the accumulation of Cd in the brain and the deterioration of the functional activity of the central nervous system. One of the main cellular targets for Cd in the brain are astrocytes. Astrocytes provide nutrition and functional activity of neurons, as well as recovery of physical and metabolic damage. The cytoskeleton of astrocytes is built of glial fibrillary acidic protein (GFAP). GFAP participates in important functions of astrocytes and its condition reflects the astrocytes reactivity. The molecular mechanisms of the neurotoxic effects of Cd on the glial cytoskeleton remain unknown. Glioblastomas are widely used to study the cytotoxic mechanisms of various compounds, including heavy metals, as cellular models of astrocytes. Taking into account the role of oxidative stress in a cell damage, as well as the reactive response of glial cells, we study the influence of low doses of Cd on oxidative stress and expression of GFAP and glucose-6-phosphate dehydrogenase (G6PD) in U373GM cells. Doses of 2-10 μM Cd induced a dose-dependent increase in reactive oxygen species and lipid peroxidation products. The same doses inhibited the expression of the cytoskeletal marker of astrocytes (GFAP) and metabolic marker of glucose utilization (G6PD). The obtained results indicate a pronounced cytotoxic effect of low doses of Cd in the astrocytic cell model U373GM. In addition, the astroglial cytotoxicity of Cd may be mediated by oxidative damage, inhibition of glial intermediate filament expression, and glucose utilization disorders. These parameters can be promising biomarkers of toxic effects both for the assessment of human and animal health and for determining the state of the environment as a whole.

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