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PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Groups: NC (Control), AD (OA-induced), MEP (AD + 3 µg/L MEP). *
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
P < 0.05, **P < 0.001 (error bars = SD, n = 3)) qRT-PCR was used to detect the regulatory effects of MEP on the ten core genes (Bar graph of 10 core genes’ relative mRNA levels (2 method, β-actin as internal control).
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Groups: NC (Control), AD (OA-induced), MEP (AD + 3 µg/L MEP). *
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
P < 0.05, **P < 0.001 (error bars = SD, n = 3)) In this study, we integrated network toxicology, machine learning, molecular docking, and in vitro experiments to systematically explore the potential molecular mechanisms by which MEP might contribute to AD progression.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Through multi-database target screening and topological analysis, we identified 153 overlapping targets between MEP and AD, and further confirmed 10 core targets (HIF1A, IGF1R, PDGFRB, PTK2, VCAM1, CXCL12, ERBB2, ESR1, JAK2, and BCL2L1) that might mediate the pathological effects of MEP.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Functional enrichment analysis revealed that these core targets are primarily involved in key pathways such as neuroactive ligand-receptor interactions and GABAergic synapses, which are closely associated with neuronal function and cognitive processes.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Clinical dataset validation and machine learning modeling further highlighted the diagnostic potential of ten core targets, while qRT-PCR experiments also confirmed that MEP can upregulate the transcriptional expression of these ten genes in AD cell models with tau protein hyperphosphorylation, providing the evidence for the link between MEP exposure and AD-related tau pathological processes.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
HIF1A, a key transcription factor in hypoxic response, regulated neuronal survival, neuroplasticity, and energy metabolism—processes critical for maintaining normal cognitive function [37–40].Abnormal activation of HIF1A had been implicated in AD-related energy metabolism disorders and neuronal damage.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
IGF1R, as the primary receptor for IGF-1, modulated neuroplasticity, learning, and memory [41–43], and its dysregulation might disrupt neuronal homeostasis in AD.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Other core targets also played pivotal roles in AD pathogenesis: PDGFRB and PTK2 regulate neuroplasticity and synaptic function [44–48].
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
VCAM1 mediated neuroinflammation, a key driver of AD progression [49–53].
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
CXCL12 participated in neuroprotection and neuroregeneration [54–57].
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
ERBB2 and ESR1 regulated neuronal survival and amyloid-β (Aβ) deposition [58–61].JAK2 was involved in multiple pathological cascades including Aβ aggregation and tau hyperphosphorylation , and BCL2L1 inhibited neuronal apoptosis .
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Collectively, these targets reflected the multi-system dysfunction of the “neuro-glio-vascular unit” in AD, suggesting that MEP might accelerate AD pathology through synergistic interactions with these molecular pathways.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Despite the valuable insights gained, this study had several limitations that need to be addressed.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
First, the in vitro AD model used in this study has inherent limitations: OA-induced SK-N-SH cells primarily simulated tau hyperphosphorylation but did not fully recapitulate the dual pathological features of AD, namely the deposition of Aβ plaques and neurofibrillary tangles.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
As a result, the model might not capture the full complexity of AD pathogenesis, and the observed effects of MEP on ten core genes might be specific to the tau-related pathway rather than Aβ-mediated processes.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Second, SK-N-SH cells are immortalized tumor-derived cells, which differ from primary neurons in terms of physiological characteristics and responsiveness to external stimuli, potentially limiting the translational relevance of the findings to native neuronal environments.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
To address these limitations and enhance the robustness of the conclusions, future research should consider the following directions.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
First, the findings should have been validated using more mature AD cell models, such as APP/PS1 double-transgenic cell lines or Aβ oligomer-treated primary cortical neurons, which could simulate both Aβ deposition and tau hyperphosphorylation, thereby comprehensively evaluating MEP’s effects on multiple AD pathological cascades.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Second, in vivo studies should have been conducted using AD model mice (e.g., APP/PS1 transgenic mice) to investigate the effects of MEP exposure on cognitive function and pathological changes in the brain, providing preclinical evidence for the association between MEP and AD.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Third, the dose-effect relationship between MEP exposure and AD risk should have been explored, as well as potential intervention strategies to mitigate MEP-induced neurotoxicity.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Additionally, future studies (at that time) should have incorporated clinical cohort data to analyze the correlation between MEP exposure levels (e.g., in serum or cerebrospinal fluid) and AD incidence or cognitive decline, further confirming the clinical relevance of the findings.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
In conclusion, this study provided preliminary evidence that MEP might contribute to AD progression by regulating core targets, and identified key signaling pathways involved in this process.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
The limitations of the in vitro model highlight the need for more comprehensive experimental systems in future research, which would help clarify the exact molecular mechanisms of MEP-induced AD and inform the development of targeted prevention and intervention strategies for AD associated with environmental chemical exposure.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
This study indicated that MEP might impact the pathogenesis of AD-related tau pathology by targeting specific genes and associated signaling pathways.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Molecular docking demonstrated that MEP exhibited significant binding specificity to its target proteins.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Quantitative real-time polymerase chain reaction (qRT-PCR) analyses further confirmed that ten key genes could serve as critical molecular links bridging MEP exposure and the development of AD-related tau pathology.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Collectively, these findings laid a solid experimental foundation for subsequent investigations into the underlying mechanisms driving MEP-induced AD-related tau pathology.
PMC12829224
Integrating machine learning and experiments to elucidate the potential molecular mechanisms of methylparaben-induced Alzheimer’s disease: evidence from a Tau hyperphosphorylation cell model
Future research should aim to validate the correlation between MEP exposure levels and AD risk in clinical or population-based studies, while also exploring potential targeted interventions to mitigate the adverse effects of MEP on brain tissue homeostasis.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Aging is a dynamic and progressive loss of physiological integrity that leads to irreversible changes in cells and tissues, thereby increasing the risk of disability, disease, and death.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Previous studies have provided evidence that D-galactose (D-gal) mimics the natural aging process in humans.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
On the other hand, it has been shown that α-lipoic acid (α-LA) acts as an anti-inflammatory and antioxidant compound.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Therefore, this study aimed to investigate the protective effects of α-LA on D-gal-induced cellular senescence in SH-SY5Y neuroblastoma cells.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Senescence was induced in SH-SY5Y cells by D-gal, and the protective effects of α-LA against D-gal toxicity were evaluated by the assays of β-galactosidase, reactive oxygen species (ROS), and antioxidant parameters in SH-SY5Y cells.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
In addition, the mRNA expression of Bax, Bcl-2, and p53 genes was evaluated using qRT-PCR.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The results revealed that α-LA at the concentrations of 62.5 and 125 μM reduced the cytotoxicity and senescence caused by D-gal.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
α-LA also effectively reduced the ROS generation compared to the D-gal group.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Treatment with α-LA significantly modulated the levels of malondialdehyde, total thiol, and superoxide dismutase activity, which were altered by D-gal.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
In addition, treatment with α-LA decreased the expression of Bax and p53 genes, while increasing the expression of the Bcl-2 gene.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Overall, the results showed that α-LA could moderate the toxic effects of D-gal by increasing the antioxidant capacity and modulating the genes involved in apoptosis, and it deserves further studies.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The aging process causes irreversible changes in the molecules, cells, tissues, and organs of living organisms (12).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Numerous factors contribute to the aging process in the body, including DNA damage, mutations, telomere shortening, and malfunctioning of the DNA repair system.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Besides atherosclerotic plaques, amyloid, advanced glycation end products, and inflammatory cytokines, other factors contribute to aging (3).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Eventually, reactive oxygen species (ROS) in the body increase due to an imbalance between the antioxidant and oxidant systems.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
By damaging macromolecules such as DNA, lipids, and proteins, ROS causes dysfunction of mitochondria, which is one of the main causes of aging (3).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
D-galactose (D-gal) is naturally present in the human body, including the brain.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Galactose oxidase converts D-gal to aldose and hydrogen peroxide, while aldose reductase converts it to galactitol, a toxic metabolite that leads to oxidative stress and inflammation.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Various foods, such as dried figs, honey, and celery, are rich in D-gal.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The brain is susceptible to oxidative stress because of its limited antioxidant defenses, high metabolic rate, and abundance of fatty tissue compared to other organs in the body.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Long-term exposure to D-gal is widely recognized to cause aging (456).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Metformin, a biguanide-class drug, is primarily used to manage hyperglycemia in patients with type 2 diabetes mellitus.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Its therapeutic actions are largely attributed to the activation of adenosine monophosphate-activated protein kinase (AMPK), enhancement of insulin sensitivity, stimulation of glycolysis, and inhibition of hepatic gluconeogenesis.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Beyond its glucose-lowering effects, metformin has demonstrated a range of beneficial properties, such as anti-inflammatory, antioxidant, and neuroprotective activities (7).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Moreover, numerous studies have revealed the anti-aging and anti-senescence properties of metformin (289).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Given the well-documented properties, metformin was selected as the positive control in this study.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The antioxidant α-lipoic acid (α-LA) was extracted from pig liver by Reed in 1951 and can be found in many foods (10).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The production of α-LA occurs in the mitochondria of animal and plant cells, as well as in microorganisms (11).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
α-LA is highly effective as a neuroprotective antioxidant because it penetrates the blood-brain barrier and is uniformly absorbed throughout the peripheral and central nervous system (12).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
α-LA is an organosulfur molecule that can neutralize ROS and reduce the activity of tissue antioxidant enzymes like superoxide dismutase (SOD) (1314).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Various studies have also shown the anti-cancer effects of α-LA in prostate, lung, breast, and colon cancers (1516171819).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
However, no study has evaluated the anti-aging effects of α-LA in SH-SY5Y neuroblastoma cells.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The SH-SY5Y cells originated from a subclone of the parent cell line SK-N-SH.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The SH-SY5Y cell line is frequently used as a model for neurotoxicity evaluation of chemicals and toxic drugs in numerous neurodegenerative disorders, primarily due to its human origin, neuronal properties, and the simplicity of its maintenance (220).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Therefore, this study aimed to evaluate the antioxidant and anti-apoptotic effects of α-LA in D-gal-induced toxicity in SH-SY5Y cells.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The SH-SY5Y neuroblastoma cells were obtained from the Pasteur Institute (Tehran, Iran).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The Dulbecco’s modified Eagle medium (DMEM), along with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin (Gibco, UK), was used for cell culture.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The cells were maintained at 37 °C with a 5% CO2 atmosphere in a humidified incubator.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
D-gal, α-LA, and metformin (Met) were purchased from Sigma-Aldrich (USA).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
2'-7'-dichlorodihydrofuorescein diacetate (DCFH-DA) cellular ROS assay kit was obtained from Abcam (Cambridge, United Kingdom).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) powder and dimethyl sulfoxide (DMSO) were supplied from Sigma-Aldrich (St. Louis, MO, USA).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Ortho-nitrophenyl beta-D-galactopyranoside (ONPG) was purchased from Solar Bio (Beijing, China).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The cytotoxicity of α-LA, D-gal, and Met in SH-SY5Y cells was carried out using the MTT assay.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
For this, the cells were seeded in 96-well plates (1 × 10 cells/well) and incubated for 24 h. Then, various concentrations of α-LA (0-3000 μM), D-gal (0-400 mM), and Met (0-20 mM) were applied to cells for 24 h. Subsequently, the cells were incubated with 100 μL medium containing MTT for 3 h. Afterwards, 150 μL of DMSO was added, and the optical density was measured at 570 nm by a plate reader.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
To determine the protective effects of α-LA and Met against D-gal-induced senescence, 1 × 10 SH-SY5Y cells were seeded in 96-well plates and subsequently divided into 6 groups as follows: A. the cells without any treatment (untreated group) as a negative control group; B. the cells treated with 155 mM of D-gal (D-gal group); C. the cells pre-treated with 31.25, 62.5, and 125 μM of α-LA for 24 h, followed by treatment with D-gal (155 mM) for a further 24 h as D-gal + α-LA 31.25, D-gal + α-LA 62.5, and D-gal + α-LA 125 groups, respectively; D. the cells pre-treated with 5 mM of Met for 24 h, followed by treatment with D-gal (155 mM) for a further 24 h (D-gal + Met group).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The D-gal + Met group was assigned as the positive control group.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Finally, cell viability was assessed using the MTT assay as mentioned above.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
All samples were tested in triplicate.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Senescence-associated β-galactosidase (SA-β-Gal) activity was examined as previously described (21).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Briefly, 50 μL of cell lysate supernatant, 50 μL of 0.1 M citrate buffer, 100 μL of 4 mg/mL ONPG solution, and 2 μL of MgCl2 at a concentration of 1 mM were mixed and incubated at 37 °C until a faint yellow color developed.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Then, 200 μL of sodium carbonate (Na2CO3) 1 M was added, and the optical absorbance of the solution was read at 420 nm by a spectrophotometer.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
For this purpose, the DCFH-DA ROS assay kit was used according to the protocol (22).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
DCFH- DA can be oxidized by intracellular ROS or peroxides to produce the fluorescent compound dichlorofluorescein (DCF) (23).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
For this assay, the SH-SY5Y cells (25 × 10 cells/well) were cultured in a 96-well dark-sided culture plate for 24 h. After that, the cells were washed with 100 μL of 1× buffer, followed by 30-45 min incubation with 100 μL of 25 μM DCFH-DA solution in a dark place at 37 °C.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Then, the cells were treated with 62.5 and 125 μM of α-LA and 5 mM of Met along with 155 mM D-gal for 24 h. Untreated cells and tert-butyl hydroperoxide (TBHP) were used as the negative and positive control groups, respectively.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Finally, the fluorescence intensity (excitation: 485/emission: 535) was recorded with the fluorescence plate reader.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Malondialdehyde (MDA), as a final product of lipid peroxidation, was measured by the colorimetric method (24).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Briefly, the cell lysate (0.5 mL) was mixed with 2 mL of hydrochloric acid (HCl), 1 mL of 10% trichloroacetic acid, and 1.5 mL of 0.67% thiobarbituric acid.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The mixture was incubated for 30 min at 95 °C.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
After cooling the samples, 0.025 mL of HCl and 1.5 mL of L-butanol were added.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Finally, the mixtures were centrifuged for 10 min at 1000 rpm, and the absorbance of the supernatants was read at 532 nm.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The evaluation of SOD activity was conducted using the procedure outlined previously (25).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Briefly, 60 μL of cell lysate was added to each well of a 96-well plate.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Then, 6 μL of MTT solution (0.5 mg/mL) and 15 μL of pyrogallol solution (0.1 mg/mL) were added and incubated for 10 min.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Following that, 150 μL of DMSO was added to each well, and then the absorbance was measured at 570 nm.
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
Total thiol levels were evaluated using 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), a reagent that reacts with the SH groups (26).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
For this, 50 μL of cell lysate was mixed with 1 mL of Tris-EDTA buffer (pH 8.6), and the absorbance at 412 nm was recorded (A1).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
After that, 20 μL of 10 mM DTNB reagent was added, and the absorbance was recorded after 10 min (A2).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
The DTNB reagent absorbance was recorded as blank (B).
PMC12614211
The protective effects of α-lipoic acid against D-galactose-induced cellular senescence in human SH-SY5Y neuroblastoma cell line
For this purpose, SH-SY5Y cells were subjected to receive 62.5 and 125 μM α-LA, 5 mM Met, and 155 mM D-gal.