Pyroptosis in Diabetic Peripheral Neuropathy and its Therapeutic Regulation

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 3839 - 3864

Опубликована: Июнь 1, 2024

Pyroptosis is a pro-inflammatory form of cell death resulting from the activation gasdermins (GSDMs) pore-forming proteins and release several factors. However, inflammasomes are intracellular protein complexes that cleave gasdermin D (GSDMD), leading to formation robust membrane pores initiation pyroptosis. Inflammasome gasdermin-mediated pore important intrinsic processes in classical pyroptotic signaling pathway. Overactivation NOD-like receptor thermal domain associated 3 (NLRP3) inflammasome triggers pyroptosis amplifies inflammation. Current evidence suggests overactivation may further induce progression cancers, nerve injury, inflammatory disorders metabolic dysfunctions. also indicates pyroptosis-dependent accelerates diabetes its frequent consequences including diabetic peripheral neuropathy (DPN). Pyroptosis-mediated reaction exacerbates DPN-mediated CNS injury. Accumulating shows molecular mechanisms trigger insulin-producing cells, development DPN. Numerous studies have suggested certain natural compounds or drugs possess promising pharmacological properties by modulating pyroptosis, thereby offering potential preventive practical therapeutic approaches for treatment management This review elaborates on underlying explores possible strategies regulating pyroptosis-regulated

Язык: Английский

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Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity

Extracellular Vesicle, Год журнала: 2023, Номер 2, С. 100027 - 100027

Опубликована: Июль 14, 2023

Exposure to environmental heavy metals such as cadmium (Cd) is often linked neurotoxicity but the underlying mechanisms remain poorly understood. Here we show that Arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles (ARMMs)–an important class of extracellular vesicles (EVs) whose biogenesis occurs at plasma membrane–protect against Cd-induced neurotoxicity. Cd increased production EVs, including ARMMs, in a human neural progenitor cell line, ReNcell CX (ReN) cells. ReN cells lack ARMMs result CRISPR-mediated ARRDC1 knockout were more susceptible toxicity evidenced by LDH well elevated level oxidative stress markers. Importantly, adding back ARRDC1-knockout significantly reduced toxicity. Consistent with this finding, proteomics data showed anti-oxidative proteins are enriched secreted from Together our study reveals novel protective role and suggests may be used therapeutically reduce caused exposure potentially other metal toxicants.

Язык: Английский

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Differential Effects of Paraquat, Rotenone, and MPTP on Cellular Bioenergetics of Undifferentiated and Differentiated Human Neuroblastoma Cells

Brain Sciences, Год журнала: 2023, Номер 13(12), С. 1717 - 1717

Опубликована: Дек. 14, 2023

Paraquat (PQ), rotenone (RO), and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are neurotoxicants that can damage human health. Exposure to these has been linked neurodegeneration, particularly Parkinson's disease. However, their mechanisms of action have not fully elucidated, nor the relative vulnerability neuronal subtypes exposures. To address this, current study investigated cytotoxic effects PQ, RO, MPTP on cellular bioenergetics oxidative stress undifferentiated neuroblastoma (SH-SY5Y) cells those differentiated dopaminergic (DA) or cholinergic (CH) phenotypes. The tested were all three cell phenotypes correlated with both concentration exposure duration. At half-maximal effective concentrations (EC50s), there significant reductions in ATP levels reduced activity mitochondrial complexes I III, a parallel increase lactate production. PQ at 10 µM significantly decreased production complex III only DA cells. RO was most potent inhibitor 1 did inhibit even induced 50% loss viability. toxicant All increased reactive oxygen species, lipid peroxidation, nuclear expression Nrf2, corresponding inhibition antioxidant enzymes catalase superoxide dismutase. biomarkers Collectively, this underscores importance dysfunction MPTP-induced cytotoxicity display differential neurotoxicants.

Язык: Английский

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An In Silico and In Vitro Assessment of the Neurotoxicity of Mefloquine

Biomedicines, Год журнала: 2024, Номер 12(3), С. 505 - 505

Опубликована: Фев. 23, 2024

Mefloquine (MQ) is a quinoline-based anti-malarial drug used for chemoprophylaxis or as treatment in combination with artesunate. Although MQ has clear anti-Plasmodium falciparum properties, it can induce neurotoxicity and undesired neuropsychiatric side effects humans. Hence, this study aimed to characterize the of using human neuroblastoma SH-SY5Y cells. The on neuronal toxicity cell viability were investigated over concentration range 1–100 µM 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) lactate dehydrogenase (LDH) assays. influence cellular bioenergetics was examined by measuring ATP levels from induction reactive oxygen species (ROS). An silico approach assess potential mediated via binding active sites acetylcholinesterase (AChE) butyrylcholinesterase (BuChE) then experimentally validated vitro enzymatic cytotoxic cells exposure duration dependent manner induced significant reduction at concentrations ≥25 after 24 h exposure. adversely impacted significantly depleted production ≥1 h. MQ-induced ROS production, which correlated apoptosis, revealed flow cytometry. In studies suggested that dual cholinesterase inhibitor one remarkably potent BuChE. Modelling data supported showed inhibited both AChE BuChE enzymes. summary, an antimalarial may impacting perturbing activity cholinesterases relevant dosage.

Язык: Английский

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Alcohol Triggers the Accumulation of Oxidatively Damaged Proteins in Neuronal Cells and Tissues

Antioxidants, Год журнала: 2024, Номер 13(5), С. 580 - 580

Опубликована: Май 8, 2024

Alcohol is toxic to neurons and can trigger alcohol-related brain damage, neuronal loss, cognitive decline. Neuronal cells may be vulnerable alcohol toxicity damage from oxidative stress after differentiation. To consider this further, the of undifferentiated SH-SY5Y was compared with that had been acutely differentiated. Cells were exposed over a concentration range 0–200 mM for up 24 h effects on cell viability evaluated via MTT LDH assays. Effects mitochondrial morphology examined transmission electron microscopy, functionality using measurements ATP production reactive oxygen species (ROS). reduced depleted levels in concentration- exposure duration-dependent manner, more toxicity. resulted neurite retraction, altered morphology, increased ROS proportion concentration; these peaked 3 6 exposures significantly higher differentiated cells. Protein carbonyl content (PCC) lagged behind 12 h, increasing concentration, Carbonylated proteins characterised by their denatured molecular weights overlapped those adult post-mortem tissue, PCC alcoholic subjects than matched controls. Hence, potentially tissue accumulation oxidatively damaged proteins.

Язык: Английский

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Prospecting Pharmacologically Active Biocompounds from the Amazon Rainforest: In Vitro Approaches, Mechanisms of Action Based on Chemical Structure, and Perspectives on Human Therapeutic Use

Pharmaceuticals, Год журнала: 2024, Номер 17(11), С. 1449 - 1449

Опубликована: Окт. 30, 2024

The Amazon rainforest is an important reservoir of biodiversity, offering vast potential for the discovery new bioactive compounds from plants. In vitro studies allow investigation biological processes and interventions in a controlled manner, making them fundamental pharmacological biotechnological research. These approaches are faster less costly than vivo studies, providing standardized conditions that enhance reproducibility precision data. However, methods have limitations, including inability to fully replicate complexity living organism absence complete physiological context. Translating results models not always straightforward, due differences pharmacokinetics interactions. this context, aim literature review assess advantages disadvantages search drugs Amazon, identifying challenges limitations associated with these comparing testing. Thus, bioprospecting involves evaluating plant extracts through bioassays investigate pharmacological, antimicrobial, anticancer activities. Phenolic terpenes frequently identified as main agents, exhibiting antioxidant, anti-inflammatory, antineoplastic Chemical characterization, molecular modifications, development delivery systems, such nanoparticles, highlighted improve therapeutic efficacy. Therefore, offers great drugs; however, significant challenges, standardization extraction need clinical trials, must be overcome become viable medications.

Язык: Английский

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Preliminary in vitro evaluation of the cytoprotective effects of clarified açaí (Euterpe oleracea MART.) pulp on African green monkey kidney cells (VERO) treated with the antifungal fluconazole

Indian Journal of Experimental Biology, Год журнала: 2024, Номер 62(02)

Опубликована: Янв. 31, 2024

Açaí (Euterpe oleracea MART.) has been the target of several studies due to its strong antioxidant potential and possible cytoprotective effect, thus providing health benefits population. Fluconazole is a widely known used drug in treatment fungal diseases. However, literature shows that this can show cytotoxic effects, as well cause DNA damage. In regard, present study aims assess putative effect clarified açaí (CA) pulp extract on VERO cells exposed fluconazole. It was observed MTT assay CA able increase viability antifungal agent three different times exposure (24, 48 72 h). Similarly, results comet demonstrated decrease genotoxic effects fluconazole significantly. Thus, we conclude that, under assessed conditions, against damage caused by

Язык: Английский

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Economic, nutritional, and innovative aspects of non-conventional Brazilian fruits in the international novel foods market

Food Research International, Год журнала: 2024, Номер 197, С. 115223 - 115223

Опубликована: Окт. 22, 2024

Язык: Английский

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