Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18
Опубликована: Март 13, 2024
The blood brain barrier (BBB) plays a crucial role in maintaining homeostasis by selectively preventing the entry of substances from peripheral into central nervous system (CNS). Comprised endothelial cells, pericytes, and astrocytes, this highly regulated encompasses majority brain’s vasculature. In addition to its protective function, BBB also engages significant crosstalk with perivascular macrophages (MΦ) microglia, resident MΦ brain. These interactions play pivotal modulating activation state cells comprising BBB, as well MΦs themselves. Alterations systemic metabolic inflammatory states can promote cell dysfunction, reducing integrity potentially allowing factors leak CNS compartment. This may mediate MΦs, initiate further immune responses within parenchyma, suggesting neuroinflammation be triggered signaling periphery, without primary injury or disease originating CNS. intricate interplay between periphery through highlights importance understanding microglia mediating challenges. Despite recent advancements, our is still early stages, leaving gap knowledge. However, emerging research shedding light on involvement at various conditions, including infections, diabetes, ischemic stroke. review aims provide comprehensive overview current investigating relationship health disease. By exploring these connections, we hope advance challenges their impact pathology. Uncovering hold promise for development novel therapeutic strategies neurological conditions that involve vascular mechanisms.
Язык: Английский
Процитировано
35Silymarin and Inflammation: Food for Thoughts
Antioxidants, Год журнала: 2024, Номер 13(1), С. 98 - 98
Опубликована: Янв. 14, 2024
Inflammation is a vital defense mechanism, creating hostile conditions for pathogens, preventing the spread of tissue infection and repairing damaged tissues in humans animals. However, when inflammation resolution delayed or compromised as result its misregulation, process proceeds from acute phase to chronic inflammation, leading development various illnesses. It proven that redox balance disturbances oxidative stress are among major factors inducing NF-κB over-inflammation. Therefore, anti-inflammatory properties natural antioxidants have been widely tested vitro vivo systems. Accumulating evidence indicates silymarin (SM) main constituent silibinin/silybin (SB) great potential an anti-inflammation agent. The mechanism SM/SB action attributed inhibition TLR4/NF-κB-mediated signaling pathways downregulated expression pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, IL-12, IL-23, CCL4, CXCL10, etc. Of note, same model systems, was able upregulate cytokines (IL-4, IL-10, IL-13, TGF-β, etc.) lipid mediators involved inflammation. inflammatory were clearly demonstrated systems based on immune (macrophages monocytes) non-immune (epithelial, skin, bone, connective cancer) cells. At time, confirmed number models, toxicity nonalcoholic fatty liver disease, ischemia/reperfusion stress-induced injuries, ageing exercising wound healing many other relevant seems likely activities key elements health-promoting these phytochemicals.
Язык: Английский
Процитировано
16Thiamethoxam at environmentally relevant concentrations induces neurotoxicity in zebrafish larvae through binding with multiple receptors
Eco-Environment & Health, Год журнала: 2025, Номер 4(1), С. 100133 - 100133
Опубликована: Янв. 18, 2025
Thiamethoxam (THM) is one of the most widely used insecticides globally, which was designed to selectively target nicotinic acetylcholine receptors (nAChRs) in insect nervous system and generally considered safe for non-targeted organisms. However, increasing evidence has demonstrated its neurotoxicity aquatic organisms, though underlying mechanisms, especially at environmentally relevant concentrations, remain largely unclear. In this study, swimming distance zebrafish significantly shortened by 14.06%-21.64% after exposure THM 10-1000 ng/L. This behavioral impairment may result from damage visual systems, as confirmed notable apoptosis, histological analysis eyes, differential expression numerous genes. Molecular docking biomarkers assays found that can bind with nAChR multiple hormone receptors, binding energies varying -3.75 -6.74 kcal/mol. Consequently, concentrations a neurotransmitter (acetylcholine) related hormones (cortisol, triiodothyronine, thyroxine, thyroid-stimulating hormone) were affected. Further investigations using weighted gene correlation network metabolomics suggest enter cell via endocytosis potentially activating MAPK signaling pathway. activation disrupt purine pyrimidine metabolism nucleus, ultimately leading apoptosis neurotoxicity. study reveals THM, even poses neurological risks underscore need urgent attention ecological impacts environments.
Язык: Английский
Процитировано
1Sesquiterpene nootkatone counteracted the melamine-induced neurotoxicity via repressing of oxidative stress, inflammatory, and apoptotic trajectories
Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 165, С. 115133 - 115133
Опубликована: Июль 14, 2023
Melamine (ML), a chemical substance of high nitrogen content, is used as food adulterant. Former evidences implied that ML could induce variety toxic effects including neurotoxicity and cognitive impairment. Therefore, the aim this study was to delineate protective effect nootkatone (NK) against ML-induced neural adverse effects. Rats were orally pretreated with NK (5 10 mg/kg) prior oral administration (700 for period 28 days. Our findings unveiled remarkable alleviating on MK-induced neurobehavioral disturbance in open field test. Furthermore, lessened ML-caused increases acetylcholine esterase level brain tissue exposed rats. also decreased oxidative stress represented by elevated levels SOD, CAT, GSH along MDA NO levels. Upregulated mRNA expression NRF-2 HO-1 noticed after administration. Remarkable anti-inflammatory impact prominent IL-1β, TNF-α downregulated NF-κB TLR-4 gene NK-treated Noteworthily, pre-treatment immune reaction RAGE HMGB-1 induced exposure. Brain histological examination validated obtained biochemical molecular results. To sum up, these outcomes reveal successfully alleviated damage via blocking stress, inflammatory signaling pathways. Consequently, our may suggest new effective therapeutic supplement treatment ML-mediated rats inhibition HMGB-1-RAGE/TLR-4/NF-κB.
Язык: Английский
Процитировано
12Nootkatone Mitigated Melamine-Evoked Hepatotoxicity by Featuring Oxidative Stress and Inflammation Interconnected Mechanisms: In Vivo and In Silico Approaches
Toxics, Год журнала: 2023, Номер 11(9), С. 784 - 784
Опубликована: Сен. 15, 2023
Melamine (ML) is a common environmental contaminant, commonly used in food fraud, representing serious health hazard and jeopardizing human animal health. Recently, nootkatone (NK), naturally occurring sesquiterpenoid, has garnered considerable attention due to its potential therapeutic advantages. We investigated the mechanisms underlying protective effects of NK against ML-induced liver injury rats. Five groups were utilized: control, ML, NK10, ML-NK5, ML-NK10. ML induced substantial hepatotoxicity, including alterations biochemical parameters histology. The oxidative distress triggered by increased generation malondialdehyde (MDA) nitric oxide (NO) decreased levels reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) activities. In addition, expression nuclear factor-erythroid 2-related factor 2 (Nrf2) kappa beta (NF-κB) observed hepatocytes, which indicated occurrence inflammatory changes following exposure. These alleviated supplementation dose-dependent manner. data revealed that favorable attributed, at least part, antioxidant anti-inflammatory properties. Moreover, our results supported molecular docking studies good fit interactions between enzymes. Thus, current study demonstrated new additive for prevention or treatment toxicity.
Язык: Английский
Процитировано
11Thiamethoxam Exposure Impairs Oocyte Maturation via Induction of Lipid Metabolism and Mitochondrial Dysfunctions in Porcine
Reproduction in Domestic Animals, Год журнала: 2025, Номер 60(3)
Опубликована: Март 1, 2025
ABSTRACT Neonicotinoid insecticides (NEOs) are the most widely used pesticides in modern agriculture, and there residues environment food. Thiamethoxam (TMX) has been proven to destroy ovarian homeostasis of mice vivo reduce development porcine oocytes vitro. However, whether TMX can interfere with oocyte maturation its potential mechanism remains unknown. This study indicated that affects expansion cumulus cells, destroys balance lipid metabolism, damages mitochondrial function. treatment decreased expression genes related cell expansion, synthesis synthesis. Collectively, results confirm exposure damage produce reproductive toxicity by inducing metabolism dysfunction porcine.
Язык: Английский
Процитировано
0Toxicological impact of Thiamethoxam on adult male rats: Histopathological, biochemical, and oxidative DNA damage assessment
Toxicology Reports, Год журнала: 2025, Номер 14, С. 101983 - 101983
Опубликована: Март 15, 2025
Thiamethoxam (TMX), a widely used second-generation neonicotinoid insecticide, has raised concerns due to its toxic effects on non-target species, including mammals. Its prolonged use is associated with hepatotoxicity, nephrotoxicity, and reproductive damage. This study evaluates the dose-dependent biochemical, histopathological, genetic of TMX in male albino rats, emphasizing impact liver, kidney, systems. Forty Wistar rats were assigned control three experimental groups treated at 26, 39, 78 mg/kg/day over eight weeks. Key biochemical markers such as Alanine transaminase (ALT), Aspartate (AST), urea, creatinine oxidative stress indicators (Catalase (CAT), Glutathione (GSH), Malondialdehyde (MDA), parameters (testosterone, sperm count, motility) analyzed. Histopathological examination testes was performed, alongside evaluation Deoxyribonucleic Acid (DNA) damage testicular tissue. exposure caused significant increases liver kidney function stress. Reproductive toxicity evident, reduced testosterone levels, impaired parameters, histopathological Notably, induced DNA tissue, indicated by increased levels 8-hydroxy-2'-deoxyguanosine. highlights TMX's systemic manner, key mechanisms. The findings underscore need for stricter regulatory measures further exploration protective strategies mitigate TMX-induced toxicity.
Язык: Английский
Процитировано
0Biochemical Studies on the Therapeutic Effect of Naja nubiae Venom Against Melamine Induced Hepatotoxicity in Albino Rats
Food Science & Nutrition, Год журнала: 2025, Номер 13(4)
Опубликована: Апрель 1, 2025
ABSTRACT Illegal melamine analogs are added to food make it appear as though contains more protein. These substances have negative impacts on both humans and animals in high quantities. The present paper examines how cobra venom shields rats from melamine‐induced hepatotoxicity. current study was conducted six groups of adult male rats, follows: group I (negative control): I.P. injected with distilled water, II (SV10 μg/kg):I.P 10 μg/kg venom, III (SV20 μg/kg): 20 IV (melamine): orally 700 mg/kg melamine, V (melamine + SV10 treated VI SV20 venom. Treatment snake ameliorated liver functions increased apoptotic level marker Caspase‐3, decreased anti‐apoptotic BAX. Also, inflammatory IL‐2 expression IL‐10, INF‐γ. treatment hepatotoxicity induced by albino rats.
Язык: Английский
Процитировано
0Exploring the toxicity of thiamethoxam on aquatic ecosystems: an overarching assessment of biochemical parameters, genotoxicity, fish flesh residues and histological alterations in Nile tilapia
Environmental Pollutants and Bioavailability, Год журнала: 2025, Номер 37(1)
Опубликована: Апрель 14, 2025
Язык: Английский
Процитировано
0Unveiling the link: Neonicotinoids and elevated cardiometabolic risks in Chinese rural residents–from a prospective cohort study combing mendelian randomization study
Journal of Hazardous Materials, Год журнала: 2024, Номер 476, С. 135170 - 135170
Опубликована: Июль 9, 2024
Язык: Английский
Процитировано
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