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1.
Mol Cell Biochem ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38941031

ABSTRACT

Bisphenol A (BPA), a common endocrine-disrupting chemical, is found in a wide range of home plastics. Early-life BPA exposure has been linked to neurodevelopmental disorders; however, the link between neuroinflammation, pyroptosis, and the development of psychiatric disorders is rarely studied. The current study attempted to investigate the toxic effect of BPA on inflammatory and microglial activation markers, as well as behavioral responses, in the brains of male rats in a dose- and age-dependent manner. Early BPA exposure began on postnatal day (PND) 18 at dosages of 50 and 125 mg/kg/day. We started with a battery of behavioral activities, including open field, elevated plus- and Y-maze tests, performed on young PND 60 rats and adult PND 95 rats. BPA causes anxiogenic-related behaviors, as well as cognitive and memory deficits. The in vivo and in silico analyses revealed for the first time that BPA is a substantial activator of nuclear factor kappa B (NF-κB), interleukin (IL)-1ß, -2, -12, cyclooxygenase-2, and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, with higher beclin-1 and LC3B levels in BPA rats' PFC and hippocampus. Furthermore, BPA increased the co-localization of caspase-1 immunoreactive neurons, as well as unique neurodegenerative histopathological hallmarks. In conclusion, our results support the hypothesis that neuroinflammation and microglial activation are involved with changes in the brain after postnatal BPA exposure and that these alterations may be linked to the development of psychiatric conditions later in life. Collectively, our findings indicate that BPA triggers anxiety-like behaviors and pyroptotic death of nerve cells via the NF-κB/IL-1ß/NLRP3/Caspase-1 pathway.

2.
Aquat Toxicol ; 272: 106971, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38843741

ABSTRACT

Bisphenol A (BPA), a common industrial chemical with estrogenic activity, has recently gained attention due to its well-documented negative effects on humans and other organisms in the environment. The potential immunotoxicity and neurotoxicity of BPA remain poorly understood in marine invertebrate species. Therefore, the impacts of exposure to BPA on a series of behaviours, immune responses, oxidative stress, neural biomarkers, histology, and the ultrastructure of gills were investigated in the date mussel, Lithophaga lithophaga. After 28 days of exposure to 0.25, 1, 2, and 5 µg/L BPA, hemolymphs from controls and exposed date mussels were collected, and the effects of BPA on immunological parameters were evaluated. Moreover, oxidative stress and neurochemical levels were measured in the gills of L. lithophaga. BPA reduced filtration rates and burrowing behaviour, whereas a 2 µg/L BPA resulted in an insignificant increase after 24 h. The exposure of date mussels to BPA significantly increased total hemocyte counts, a significant reduction in the diameter and phagocytosis of hemocytes, as well as gill lysozyme level. BPA increased lipid peroxidation levels and SOD activity in gills exposed to 2 and 5 µg/L BPA, but decreased GSH levels and SOD activity in 0.25 and 1 µg/L BPA-treated date mussels. Dose-dependent dynamics were observed in the inhibition of acetylcholinesterase activity and dopamine levels. Histological and scanning electron microscope examination revealed cilia erosion, necrosis, inflammation, and hyperplasia formation in the gills. Overall, our findings suggest a relationship between BPA exposure and changes in the measured immune parameters, oxidative stress, and neurochemical disturbances, which may be factored into the mechanisms underlying BPA toxicity in marine molluscs, providing a scientific foundation for marine BPA risk assessment and indicating immunosuppression in BPA-exposed date mussels.


Subject(s)
Acetylcholinesterase , Benzhydryl Compounds , Dopamine , Gills , Hemocytes , Oxidative Stress , Phenols , Water Pollutants, Chemical , Animals , Gills/drug effects , Phenols/toxicity , Hemocytes/drug effects , Benzhydryl Compounds/toxicity , Water Pollutants, Chemical/toxicity , Acetylcholinesterase/metabolism , Dopamine/metabolism , Oxidative Stress/drug effects , Bivalvia/drug effects , Behavior, Animal/drug effects , Cholinesterase Inhibitors/toxicity , Lipid Peroxidation/drug effects
3.
Environ Sci Pollut Res Int ; 30(50): 109041-109062, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37768489

ABSTRACT

Bisphenol A (BPA), a common plastic additive, has been demonstrated mechanistically to be a potential endocrine disruptor and to affect a variety of body functions in organisms. Although previous research has shown that BPA is toxic to aquatic organisms, the mechanism of neurotoxic effects in marine bivalves remains unknown. The current study aimed to elucidate the neurotoxic effects of BPA when administered at different concentrations (0.25, 1, 2, and 5 µg/L) for twenty-eight days in the ganglia of a bivalve model, the Mediterranean mussel (Lithophaga lithophaga), which is an ecologically and economically important human food source of bivalve species in the Mediterranean Sea. Our findings revealed an increase in behavioural disturbances and malondialdehyde levels in treated mussel ganglia compared to the control group. Furthermore, superoxide dismutase activity increased in the ganglia of L. lithophaga treated with 0.25 and 2 µg/L. However, at BPA concentrations of 1 and 5 µg/L, SOD activity was significantly reduced, as was total glutathione concentration. BPA causes neurotoxicity, as evidenced by concentration-dependent inhibition of acetylcholinesterase, dopamine, and serotonin. After chronic exposure to BPA, neurons showed distortion of the neuronal cell body and varying degrees of pyknosis. The ultrastructure changes in BPA-treated groups revealed the lightening of the nucleoplasm and a shrunken nuclear envelope. Overall, our findings suggest that BPA exposure altered antioxidation, neurochemical biomarkers, histopathological, and ultrastructural properties, resulting in behavioural changes. As a result, our findings provide a basis for further study into the toxicity of BPA in marine bivalves.


Subject(s)
Acetylcholinesterase , Mytilidae , Animals , Humans , Phenols/toxicity , Benzhydryl Compounds/toxicity
4.
Article in English | MEDLINE | ID: mdl-37330179

ABSTRACT

Environmental contaminants with estrogenic activity have recently received attention due to the potential harm they could cause to humans and wildlife. To assess the toxic effects of bisphenol A (BPA) on marine mussels, Lithophaga lithophaga were exposed for 4 weeks to 0, 0.25, 1, 2, and 5 µg/L BPA. Aside from DNA damage, a behavioural study including valve closure duration (VCD), valve opening duration (VOD), levels of malondialdehyde (MDA), and total glutathione, as well as superoxide dismutase (SOD) and ATPase activities in adductor muscle extracts, and histopathological examination of the adductor muscle and foot were performed. The behavioural response was marked by an increase in the percentage of VCD and a decrease in the percentage of VOD during 8 h. Furthermore, BPA treatments resulted in a significant concentration-dependent increase in muscle MDA and total glutathione levels. However, when compared to controls, SOD and ATPase activity was significantly reduced in the adductor muscles of BPA treatments. Histological examination of the adductor and foot muscles revealed qualitatively distinct abnormalities. DNA damage was strongly induced in a concentration-dependent manner. Our findings suggested that BPA exposure altered detoxification, antioxidation, ATPase activity, histopathological characteristics, and DNA damage, which resulted in behavioural changes. The multi-biomarker approach used suggests that clear relationships exist between genotoxic and higher-level effects in some cases, which could be used as an integrated tool to evaluate various long-term toxic effects of BPA.


Subject(s)
Benzhydryl Compounds , Glutathione , Adenosine Triphosphatases , Benzhydryl Compounds/toxicity , DNA Damage , Glutathione/metabolism , Muscles/metabolism , Oxidative Stress , Superoxide Dismutase/metabolism , Animals
5.
Phytother Res ; 37(6): 2693-2737, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37195042

ABSTRACT

Neurodegenerative disorders are heterogeneous, debilitating, and incurable groups of brain disorders that have common features including progressive degeneration of the structure and function of the nervous system. Phytoestogenic-isoflavones have been identified as active compounds that can modulate different molecular signaling pathways related to the nervous system. The main aim is to shed the light on the molecular mechanisms followed by phytoestrogen-isoflavones profound in the Trifolium pratense and discuss the latest pharmacological findings in the treatment of neurodegenerative disorders. Data were collected using different databases. The search terms used included "Phytoestrogens," "Isoflavones," "neurodegenerative disorders," "Neuronal plasticity," etc., and combinations of these keywords. As a result, this review article mainly demonstrates the potential neuroprotective properties of phystoestrogen-isoflavones present in the Trifolium pratense (Red clover), particularly in neurodegenerative disorders. Phytochemical studies have shown that Trifolium pratense mainly includes more than 30 isoflavone compounds. Among them, phytoestrogen-isoflavones, such as biochanin A, daidzein, formononetin, genistein (Gen), etc.,are characterized by potent neuroprotective properties against different neurodegenerative disorders. There are preclinical and clinical scientific evidence on their mechanisms of action involve molecular interaction with estrogenic receptors, anti-inflammatory, anti-oxidative, antiapoptotic, autophagic inducing, and so on. phytoestrogen-isoflavones are the major bioactive components in the Trifolium pratense that exhibit therapeutic efficacy in the case of neurodegenerative disorders. This review provides detailed molecular mechanisms targeted by phytoestrogen-isoflavones and experimental key findings for the clinical use of prescriptions containing Trifolium pratense-derived isoflavones for the treatment of neurodegenerative disorders.


Subject(s)
Isoflavones , Neuroprotective Agents , Trifolium , Phytoestrogens/pharmacology , Phytoestrogens/therapeutic use , Trifolium/chemistry , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Isoflavones/pharmacology , Isoflavones/therapeutic use , Plant Extracts/pharmacology , Plant Extracts/therapeutic use
6.
Phytochemistry ; 202: 113293, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35780924

ABSTRACT

Neurodegenerative and neuropsychiatric illnesses are prevalent and life-threatening disorders characterized by a wide range of clinical syndromes and comorbidities, all of which have complex origins and share common molecular pathomechanisms. Although the pathophysiology of neurological illnesses is not completely understood, researchers have discovered that several ion channels and signalling pathways may have played a role in disease pathogenesis. Active substances from Astragalus sp. are being employed for nutrition, and their usefulness in the treatment of neurological illnesses is receiving more attention. Because their extracts and active components exert different pharmacological effects on a variety of ailments, they have a long history of usage as a cure for various diseases. This review summarizes the research work on Astragalus and their biologically active constituents as potential candidates for the protection against and treatment of neurodegenerative and neuropsychiatric disorders to show the potential efficacy of Astragalus sp. and its active ingredients in treating some neurological diseases. Simultaneously, the chemical structures of these active compounds, their sources, biological properties, and mechanisms are also listed. In ethnopharmacological applications, Astragalus membranaceus and spinosus have been studied as traditional medicines worldwide. The chemical constituents of Astragalus species mainly comprise terpenoids, flavonoids, and polysaccharides. The extracts and phytochemical compounds of Astragalus species exhibit various pharmacological activities, including antioxidant, anti-inflammatory, anticancer, antitumor, anticonvulsive, immunomodulatory, and other activities. Based on the current literature, we conclude that Astragalus is a promising dietary herb with multiple potential signal modulating applications that mainly include the modulation of neurotransmitters and receptors, anti-inflammatory activities, inhibition of amyloid aggregation, induction of myelin sheath repair and neurogenesis, as well as activation of the signalling pathways relevant to neurological diseases.


Subject(s)
Astragalus Plant , Nervous System Diseases , Neuroprotective Agents , Saponins , Anti-Inflammatory Agents , Astragalus Plant/chemistry , Astragalus propinquus/chemistry , Nervous System Diseases/drug therapy , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Saponins/chemistry
7.
J Genet Eng Biotechnol ; 19(1): 123, 2021 Aug 21.
Article in English | MEDLINE | ID: mdl-34417930

ABSTRACT

BACKGROUND: γ-Aminobutyric acid sub-type A receptors (GABAARs) are the most prominent inhibitory neurotransmitter receptors in the CNS. They are a family of ligand-gated ion channel with significant physiological and therapeutic implications. MAIN BODY: GABAARs are heteropentamers formed from a selection of 19 subunits: six α (alpha1-6), three ß (beta1-3), three γ (gamma1-3), three ρ (rho1-3), and one each of the δ (delta), ε (epsilon), π (pi), and θ (theta) which result in the production of a considerable number of receptor isoforms. Each isoform exhibits distinct pharmacological and physiological properties. However, the majority of GABAARs are composed of two α subunits, two ß subunits, and one γ subunit arranged as γ2ß2α1ß2α1 counterclockwise around the center. The mature receptor has a central chloride ion channel gated by GABA neurotransmitter and modulated by a variety of different drugs. Changes in GABA synthesis or release may have a significant effect on normal brain function. Furthermore, The molecular interactions and pharmacological effects caused by drugs are extremely complex. This is due to the structural heterogeneity of the receptors, and the existence of multiple allosteric binding sites as well as a wide range of ligands that can bind to them. Notably, dysfunction of the GABAergic system contributes to the development of several diseases. Therefore, understanding the relationship between GABAA receptor deficits and CNS disorders thus has a significant impact on the discovery of disease pathogenesis and drug development. CONCLUSION: To date, few reviews have discussed GABAA receptors in detail. Accordingly, this review aims to summarize the current understanding of the structural, physiological, and pharmacological properties of GABAARs, as well as shedding light on the most common associated disorders.

8.
Food Chem Toxicol ; 94: 112-27, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27234133

ABSTRACT

The present study was carried out to evaluate the potential protective role of co-administration of Ginkgo biloba, Trifolium pretenseagainst sodium arsenite-induced neurotoxicity in different parts of brain (Cerebral cortex, Hippocampus, striatum and Hind brain) and in the spinal cord of rats. Sodium arsenite caused impairment in the acquisition and learning in all the behavioral tasks and caused significant increase in tumor necrosis factor-α,thiobarbituric acid-reactive substances andlipid profile, while caused significant decrease in glutathione, total thiol content, total antioxidant capacity, acetylcholinesterase, monoamine oxidase and ATPases activities. These results were confirmed by histopathological, fluorescence and scanning electron microscopy examination of different regions of brain. From these results sodium arsenite-induced neurodegenerative disorder in different regions of brain and spinal cord and this could be mediated through modifying the intracellular brain ions homeostasis, cholinergic dysfunction and oxidative damage. The presence of Ginkgo biloba and/orTrifolium pretense with sodium arsenite minimized its neurological damages. It was pronounced that using Ginkgo biloba and Trifolium pretense in combination was more effective as protective agents compared to use eachone of them alone.


Subject(s)
Arsenites/toxicity , Brain/drug effects , Ginkgo biloba , Neuroprotective Agents/administration & dosage , Sodium Compounds/toxicity , Spinal Cord/drug effects , Trifolium , Animals , Brain/pathology , Male , Rats , Rats, Wistar , Spinal Cord/pathology
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