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PBAT-modified starch blended film are thermoplastic biodegradable materials with good properties and a wide range of applications. In this study, L-02 cells were used as an in vitro toxicity evaluation system for risk assessment of PBAT-modified starch films with migration studies obtained in different food simulants. Determination of total migration and organic matter revealed that the results were in accordance with the standard except for the total organic matter under 95% (v/v) ethanol food simulant which exceeded the standard. The CCK-8 assay showed that these compounds affect the cell viability of L-02 cells. It was observed that the compounds made the cells express increased AST, ALT, TNF-α, IL-6, IL-1ß, and ROS, and decreased SOD, GSH, and ATP. In addition, we explored the effect of migration in PBAT-modified starch composites on protein and gene expression levels in L-02 cells using a transcriptomic approach and found that the AMPK signaling pathway was affected. The expression of AMPK signaling pathway-related proteins was detected by Western Blot, and the expression levels of p-AMPK/AMPK were found to be upregulated, and those of p-mTOR/mTOR, SIRT1, PGC-1α, NRF1 and TFAM were downregulated. The above data suggest that the compounds migrating into the PBAT-modified starch film when exposed to food may induce oxidative stress and inflammation in hepatocytes, and may cause damage to hepatocytes through the AMPK pathway.
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1,4-butanediol (1,4-BD) is a known γ-hydroxybutyric acid (GHB) precursor which affects the nervous system after ingestion, leading to uncontrolled behavioral consequences. In the present study, we investigated whether 1,4-BD induces oxidative stress and inflammation in PC12 cells and evaluated the toxic effects of 1,4-BD associates with learning and memory. CCK-8 results revealed a dose-effect relationship between the cell viability of PC12 cells and 1,4-BD when the duration of action was 2 h or 4 h. Assay kits results showed that 1,4-BD decreased the levels of Glutathione (GSH), Glutathione peroxidase (GSH-px), Superoxide dismutase (SOD), Acetylcholine (Ach) and increased the levels of Malondialdehyde (MDA), Nitric oxide (NO) and Acetylcholinesterase (AchE). Elisa kits results indicated that 1,4-BD decreased the levels of synaptophysin I (SYN-1), Postsynaptic density protein-95 (PSD-95), Growth associated protein-43 (GAP-43) and increased the levels of Tumor necrosis factor alpha (TNF-α) and Interleukin- 6 (IL-6). RT-PCR results showed that the mRNA levels of PSD-95, SYN-1 and GAP-43 were significantly decreased. The expression of phosphorylation extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phosphorylation cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) proteins were significantly decreased in PC12 cells by protein blotting. Overall, these results suggest that 1,4-BD may affect synaptic plasticity via the ERK1/2-CREB-BDNF pathway, leading to Ach release reduction and ultimately to learning and memory impairment. Furthermore, oxidative stress and inflammation induced by 1,4-BD may also result in learning and memory deficits. These findings will enrich the toxicity data of 1.4-BD associated with learning and memory impairment.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Sistema de Sinalização das MAP Quinases , Acetilcolinesterase/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Butileno Glicóis , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteína GAP-43/metabolismo , Proteína GAP-43/farmacologia , Glutationa/metabolismo , Hipocampo/metabolismo , Inflamação/metabolismo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Células PC12 , Ratos , Transdução de SinaisRESUMO
Nonylphenol (NP) exposure can trigger neurotoxicity and cause learning and memory impairment. Nicotinamide mononucleotide (NMN) has a therapeutic effect on neurodegenerative diseases, but the role of NMN on NP-induced learning and memory impairment is not known. Here, we examined the mitigative effect of NMN on the impaired learning and memory ability of rats exposed to NP. The NP impaired learning and memory in rats, while the low-dose intervention with NMN significantly prolonged the step-through latency of the PAT and improved the NAMPT and NMNAT1 content in brain tissue. At the same time, the NMN intervention also increased the content of 5-HTR1A, 5-HTR4, and 5-HTR6 related to learning and memory in the hippocampus. In line with this, we found that the NMN intervention activated the SIRT1/MAO-A pathway in brain tissue. NMN intervention, especially at 125 mg/kg doses, may improve rats' NP-induced learning and memory impairment via the central 5-HT system and the NAD+/SIRT1/MAO-A pathway in the brain.
Assuntos
NAD , Mononucleotídeo de Nicotinamida , Ratos , Animais , NAD/metabolismo , Serotonina , Sirtuína 1/genética , Sirtuína 1/metabolismo , MonoaminoxidaseRESUMO
In this study, decolorized pectic polysaccharides (D-ACLP) with molecular weight (Mw) distribution of 3483- 2,023,656 Da were prepared from Amaranth caudatus leaves. Purified polysaccharides (P-ACLP) with the Mw of 152,955 Da were further isolated from D-ACLP through gel filtration. The structure of P-ACLP was analyzed by 1D and 2D NMR spectra. P-ACLP were identified as rhamnogalacturonan-I (RG-I) containing dimeric arabinose side chains. The main chain of P-ACLP was composed of â4)-α-GalpA-(1â, â2)-ß-Rhap-(1â, â3)-ß-Galp-(1â and â6)-ß-Galp-(1â. There was a branched chain of α-Araf-(1â2)-α-Araf-(1â connected to the O-6 position of â3)-ß-Galp-(1â. The GalpA residues were partially methyl esterified at O-6 and acetylated at O-3. The 28-day consecutive gavage of D-ALCP (400 mg/kg) significantly elevated the hippocampal glucagon-like peptide-1 (GLP-1) levels in rats. The concentrations of butyric acid and total short chain fatty acids in the cecum contents also increased significantly. Moreover, D-ACLP could significantly increase the gut microbiota diversity and dramatically up-regulated the abundance of Actinobacteriota (phylum) and unclassified Oscillospiraceae (genus) in intestinal bacteria. Taking together, D-ACLP might promote the hippocampal GLP-1 level through the beneficial regulation of butyric acid-producing bacteria in gut microbiota. This study contributed to making full use of Amaranth caudatus leaves for cognitive dysfunction intervention in food industry.
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Núcleo Caudado , Polissacarídeos , Animais , Ratos , Polissacarídeos/química , Pectinas/química , Espectroscopia de Ressonância Magnética , Folhas de PlantaRESUMO
Phthalate esters (PAEs) are a widespread environmental pollutant, and their ecological and environmental health risks have gradually attracted attention. To reveal the toxicity characteristics of these compounds, ten PAEs were selected as research objects to establish a cell model. CCK-8 was used to determine cell viability, Western blots were used to determine the content of Nrf2 in HepG2, and the LD50 collected for the 13 PAEs administered to rats. On this basis, 3D-QSAR models of IC50, LD50 and Nrf2 were established. The experimental results showed that as the time of PAEs exposure increased (24, 48 and 72 h), cell viability gradually decreased. The test concentration (62.5 /125/250 µM) of PAEs exposed for 48 h could significantly increase the content of Nrf2, and the 1000 µM PAEs could inhibit the content of Nrf2. The model is relatively stable and predicts well that the introduction of large and hydrophobic groups may significantly affect the toxic effects of PAEs on cells. The present study provided a potential tool for predicting the LD50 and Nrf2 of new PAEs, and provide a reference for the design of new less toxic PAEs in the future.