Excessive sulfur oxidation in endoplasmic reticulum drives an inflammatory reaction of chondrocytes in aging mice DOI Creative Commons
Kun Chen, Xianzuo Zhang, Zhi Li

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 24, 2022

Osteoarthritis, as a common joint disease among middle-aged and elderly people, has many problems, such diverse pathogenesis, poor prognosis high recurrence rate, which seriously affects patients’ physical mental health reduces their quality of life. At present, the pathogenesis osteoarthritis is not completely clear, treatment plan mainly to relieve symptoms ensure basic Therefore, it particularly urgent explore osteoarthritis. Protein, organic macromolecule plays major role in life activities, an important development disease. Through protein omics, this study found that with increase age, excessive sulfur oxidation occurred endoplasmic reticulum chondrocytes, then drove occurrence inflammatory reaction, provided direction for follow-up molecular targeted.

Language: Английский

Kynurenic Acid Plays a Protective Role in Hepatotoxicity Induced by HFPO-DA in Male Mice DOI

Jianglin Hu,

Jiayin Dai, Nan Sheng

et al.

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: 58(4), P. 1842 - 1853

Published: Jan. 16, 2024

Following its introduction as an alternative to perfluorooctanoic acid, hexafluoropropylene oxide dimer acid (HFPO-DA) has been extensively detected in various environmental matrices. Despite this prevalence, limited information is available regarding hepatotoxicity biomarkers. In study, toxicokinetic simulations indicated that under repeated treatment, HFPO-DA mice serum reached a steady state by the 4th day. To assess subacute hepatic effects and identify potential biomarkers, were administered orally at doses of 0, 0.1, 0.5, 2.5, 12.5, or 62.5 mg/kg/d for 7 d. Results revealed lowest observed adverse effect levels 0.5 hepatomegaly 2.5 injury. Serum metabolomics analysis identified 34, 58, 118 differential metabolites groups, respectively, compared control group. Based on weighted gene coexpression network analysis, eight hepatotoxicity-related identified; among them, kynurenic (KA) mouse exhibited highest correlation with liver Furthermore, liver-targeted demonstrated exposure induced metabolic migration kynurenine pathway from KA nicotinamide adenine dinucleotide, resulting activation endoplasmic reticulum stress nuclear factor kappa-B signaling pathway. Notably, pretreatment significantly attenuated injury mice, highlighting pivotal roles HFPO-DA.

Language: Английский

Citations

11
Nitrosamines crisis in pharmaceuticals − Insights on toxicological implications, root causes and risk assessment: A systematic review DOI Creative Commons

Hemanth P.R. Vikram,

Tegginamath Pramod Kumar,

Gunjan Kumar

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2023, Volume and Issue: 14(5), P. 100919 - 100919

Published: Dec. 12, 2023

The presence of N-nitroso compounds, particularly N-nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates toxicity active ingredients, drug products, excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, regulatory guidelines nitrosamines. emphasizes the molecular focusing on genotoxic, mutagenic, carcinogenic, other physiological Additionally, it addresses ongoing nitrosamine crisis, development nitrosamine-free importance sensitive detection methods precise risk evaluation. comprehensive overview will aid biologists, scientists, formulation scientists research sector, researchers involved management nitrosamine-induced promoting safer products.

Language: Английский

Citations

13
Mass Spectrometry Imaging Reveals the Morphology-Dependent Toxicological Effects of Nanosilvers on Multiple Organs of Adult Zebrafish (Danio rerio) DOI

Qingrong Xie,

Zhen Li, Yingying Chen

et al.

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: 58(23), P. 10015 - 10027

Published: May 27, 2024

Nanosilvers with multifarious morphologies have been extensively used in many fields, but their morphology-dependent toxicity toward nontarget aquatic organisms remains largely unclear. Herein, we matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to investigate the toxicological effects of silver nanomaterials various on spatially resolved lipid profiles within multiple organs adult zebrafish, especially for gill, liver, and intestine. Integrated histopathology, enzyme activity, accumulated Ag contents amounts, as well MSI results, found that nanosilvers exhibit nanotoxicity by disrupting levels producing oxidative stress. Silver nanospheres (AgNSs) had highest whereas nanoflakes (AgNFs) exhibited greater than nanowires (AgNWs). Levels differential phospholipids, such PC, PE, PI, PS, were associated nanosilver morphology. Notably, AgNSs induced organs, brain, while AgNWs AgNFs caused intestine AgNSs. Lipid functional disturbance stress further inflammation membrane damage after exposure nanosilvers, respect sphere Taken together, these findings will contribute clarifying mechanisms different zebrafish.

Language: Английский

Citations

5
Untargeted Lipidomics Revealed the Protective Effects of Cyanidin-3-O-glucoside on Bisphenol A-Induced Liver Lipid Metabolism Disorder in Rats DOI
Ruijing Liu, Yulong Jin, Bo Liu

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(2), P. 1077 - 1090

Published: Jan. 3, 2023

Bisphenol A (BPA) is an estrogenic endocrine disruptor that induces metabolic disorders. Cyanidin-3-O-glucoside (C3G) has multiple functional activities and the most abundant anthocyanin belonging to flavonoid subgroup. This study aimed investigate protective effect of C3G on BPA-induced liver lipid metabolism disorder explore its mechanism via lipidomics analysis. The results showed supplementation significantly ameliorated serum levels low-density lipoprotein cholesterol, high-density total triacylglycerols (TG), alanine aspartate aminotransferase (ALT AST). Furthermore, indicated effectively facilitated recovery differential metabolites, including TGs, phosphatidylethanolamines, phosphatidylcholines, lysophosphatidylcholines, phosphatidylinositol, cholesteryl esters, phosphatidylserine, reversed hepatic synthesis-related genes. Our suggest effective regulatory disorders metabolism.

Language: Английский

Citations

11
Characterization of hepatotoxic effects induced by pyraclostrobin in human HepG2 cells and zebrafish larvae DOI Creative Commons
Mengqi Wu,

Jinhao Bian,

Shuang Han

et al.

Chemosphere, Journal Year: 2023, Volume and Issue: 340, P. 139732 - 139732

Published: Aug. 5, 2023

Language: Английский

Citations

11
A preliminary study of combined toxicity and underlying mechanisms of imidacloprid and cadmium coexposure using a multiomics integration approach DOI
Yuankai Wang,

Ziyue Zhuang,

Guangyun He

et al.

Toxicology, Journal Year: 2025, Volume and Issue: 511, P. 154063 - 154063

Published: Jan. 21, 2025

Language: Английский

Citations

0
Insight into the Molecular Initiating Event of Mutagenic N-Nitrosamines: A Computational Study on DNA Alkylation by Their Diazonium Ions DOI Creative Commons
Shiyang Cheng, Haihua Qiu,

Wen Ding

et al.

Environmental Toxicology and Chemistry, Journal Year: 2025, Volume and Issue: 44(3), P. 777 - 785

Published: Jan. 6, 2025

Abstract N-Nitrosamines are a class of compounds that includes the potent mutagenicity and carcinogenicity many its members is distributed widely throughout human environment. DNA alkylation by their diazonium ions formed metabolically acts as molecular initiating event (MIE) links chemistry to mutagenicity. However, regiochemistry for reacting with bases still under debate. Hence, density functional theory calculations involving SN2 guanine (Gua) 14 diverse presented, results which showed mutagenicity-related shift from GuaN7- GuaO6-alkylation proceeds increasing complexity alkylating agents, along greater proportion SN1 characteristic in transition states. “high oxyphilic” “low agents may instead be “SN1” “SN2” species, respectively. As degree MIE selectivity hard−hard interactions can quantified hard soft acids theory, quantitative relationships were modeled between nucleophilic index (ω-) hydrophobicity (log P) carcinogenic potency. Therefore, mechanistic link target toxicity bridged computational chemistry.

Language: Английский

Citations

0
Synergism of Fusobacterium periodonticum and N-nitrosamines promote the formation of EMT subtypes in ESCC by modulating Wnt3a palmitoylation DOI Creative Commons

Mingjun Sun,

Zhenyan Peng,

Weitao Shen

et al.

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Aug. 28, 2024

N-Nitrosamine disinfection by-products (NAs-DBPs) have been well proven for its role in esophageal carcinogenesis. However, the of intratumoral microorganisms squamous cell carcinoma (ESCC) has not yet explored context exposure to NAs-DBPs. Here, multi-omics integration reveals

Language: Английский

Citations

2
Multi-omics analysis revealed NMBA induced esophageal carcinoma tumorigenesis via regulating PPARα signaling pathway DOI
Hu Zhang, Chao Zhao, Ying Zhang

et al.

Environmental Pollution, Journal Year: 2023, Volume and Issue: 324, P. 121369 - 121369

Published: Feb. 27, 2023

Language: Английский

Citations

4
A critical review of advances in tumor metabolism abnormalities induced by nitrosamine disinfection by-products in drinking water DOI Open Access

Mingjun Sun,

Weitao Shen, Xinxin Guo

et al.

Toxicological Sciences, Journal Year: 2024, Volume and Issue: 199(1), P. 12 - 28

Published: Jan. 30, 2024

Abstract Intensified sanitation practices amid the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak might result in increased release of chloramine disinfectants into surface water, significantly promoting formation nitrosamine disinfection by-products (DBPs) drinking water. Unfortunately, these DBPs exhibit significant genotoxic, carcinogenic, and mutagenic properties, whereas chlorinating remain global practice. The current review provides valuable insights occurrence, identification, contamination status, exposure limits, toxicity new unregulated (nitrosamine DBPs) As a result, concentrations far exceed allowable limits prolonged has potential to cause metabolic disorders, critical step tumor initiation progression. Importantly, based on research, we have concluded role nitrosamines different pathways. Remarkably, can induce chronic inflammation initiate tumors by activating sphingolipid polyunsaturated fatty acid metabolism. Regarding amino nucleotide metabolism, inhibit tryptophan metabolism de novo synthesis. Moreover, inhibition synthesis fails repair DNA damage induced nitrosamines. Additionally, accumulation lactate may act as pivotal signaling molecule communication within microenvironment. However, with advancement metabolomics, understanding causing cancer inducing abnormalities lags behind, specific mechanisms toxic effects are not clearly defined. Urgently, further studies exploring this promising area needed.

Language: Английский

Citations

1