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Journal of Chromatography. B,... Jun 2024Reactive aldehydes are a class of electrophilic low molecular weight compounds that play an essential role in physiological function and lipid peroxidation. These...
Reactive aldehydes are a class of electrophilic low molecular weight compounds that play an essential role in physiological function and lipid peroxidation. These molecules are implicated in many diseases, especially cardiovascular and neurodegenerative diseases, and are potential endogenous markers of lipid peroxidation. However, there are limited options to accurately quantify multiple reactive aldehydes in brain tissue. This study developed and validated a 3-nitrophenylhydrazine derivatization-based LC-MS/MS method to quantify four reactive aldehydes: malondialdehyde, acrolein, 4-hydroxy-2-hexenal and 4-hydroxy-2-nonenal. Method development involved comparing the sensitivity of detection between widely used derivatization reagents: 2,4-dinitrophenylhydrazine and 3-nitrophenylhydrazine. Our data showed that 3-nitrophenylhydrazine resulted in greater sensitivity. Additional method development included evaluation of hydrolysis sample pretreatment, selection of protein precipitation reagent, and optimization of derivatization conditions. The optimized conditions included no hydrolysis and use of 20 % trichloroacetic acid as the protein precipitation reagent. The optimized derivatization condition was 25 mM 3-nitrophenylhydrazine reacted at 20 °C for 30 min. The chromatographic conditions were optimized to reduce matrix effects, ion suppression, and efficient analysis time (<7-minute analytical run). The four aldehyde species were accurately quantified in brain tissue using stable-labeled internal standards. Application of this assay to a traumatic brain injury mouse model revealed significant accumulation of acrolein, 4-hydroxy-2-hexenal, and 4-hydroxy-2-nonenal at 28 days post injury. Overall, a validated method was developed to rapidly quantify the most prominent reactive aldehydes associated with lipid peroxidation during injury progression following acute brain trauma.
PubMed: 38880056
DOI: 10.1016/j.jchromb.2024.124208 -
Environmental Research Jun 2024Epidemiological evidence emphasizes air pollutants' role in chronic kidney disease (CKD). Volatile organic compounds (VOCs) contribute to air pollution, yet research on...
BACKGROUND
Epidemiological evidence emphasizes air pollutants' role in chronic kidney disease (CKD). Volatile organic compounds (VOCs) contribute to air pollution, yet research on VOCs and kidney damage, especially gender disparities, is limited.
METHODS
This study analyzed NHANES data to explore associations between urinary VOC metabolite mixtures (VOCMs) and key kidney-related parameters: estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), chronic kidney disease (CKD), and albuminuria. Mediation analyses assessed the potential mediating roles of biological aging (BA) and serum albumin in VOCM mixtures' effects on kidney damage. Sensitivity analyses were also conducted.
RESULTS
The mixture analysis unveiled a noteworthy positive association between VOCM mixtures and the risk of developing CKD, coupled with a significant negative correlation with eGFR within the overall participant cohort. These findings remained consistent when examining the female subgroup. However, among male participants, no significant link emerged between VOCM mixtures and CKD or eGFR. Furthermore, in both the overall and female participant groups, there was an absence of a significant correlation between VOCM mixtures and either ACR or albuminuria. On the other hand, in male participants, while no significant correlation was detected with albuminuria, a significant positive correlation was observed with ACR. Pollutant analysis identified potential links between kidney damage and 1,3-butadiene, toluene, ethylbenzene, styrene, xylene, acrolein, crotonaldehyde and propylene oxide. Mediation analyses suggested that BA might partially mediate the relationship between VOCM mixtures and kidney damage.
CONCLUSION
The current findings highlight the widespread exposure to VOCs among the general U.S. adult population and indicate a potential correlation between exposure to VOC mixtures and compromised renal function parameters, with notable gender disparities. Females appear to exhibit greater sensitivity to impaired renal function resulting from VOCs exposure. Anti-aging treatments may offer some mitigation against kidney damage due to VOCs exposure.
PubMed: 38879106
DOI: 10.1016/j.envres.2024.119426 -
Toxicology Jun 2024Acrolein (ACR), an unsaturated, highly reactive aldehyde, is a widespread environmental toxin. ACR exerts permanent and irreversible side effects on ovarian functions....
Acrolein (ACR), an unsaturated, highly reactive aldehyde, is a widespread environmental toxin. ACR exerts permanent and irreversible side effects on ovarian functions. Granulosa cells play a crucial role in supporting ovarian function. Thus, in this study, we investigated the toxicity effects of granulosa cells induced by ACR. Following treatment with varying ACR concentrations (0, 12.5, 25, 50, and 100μM), we observed that ACR exposure induced reactive oxygen species accumulation, mitochondrial energy metabolism disorder, and apoptosis in KGN cells (a human ovarian granulosa cell line) in a dose-dependent manner. In addition, mitochondrial biogenesis in KGN cells displayed biphasic changes after ACR exposure, with activation at a low ACR dose (12.5μM), but inhibition at higher ACR doses (≥50μM). SIRT1/PGC-1α-mediated mitochondrial biogenesis is crucial for maintaining intracellular mitochondrial homeostasis and cellular function. The inhibition/activation of the SIRT1/PGC-1α pathway in KGN cells validated its role in ACR-induced damage. The results indicated that the inhibition of the SIRT1/PGC-1α pathway aggravated ACR-induced cell damage, whereas its activation partially counteracted ACR-induced cell damage. This study attempted to uncover a novel mechanism of ACR-induced ovarian toxicity so as to provide an effective treatment option for safeguarding female reproductive health from the adverse effects of ACR.
PubMed: 38866128
DOI: 10.1016/j.tox.2024.153861 -
The AAPS Journal Jun 2024Addressing the intertwined challenges of antimicrobial resistance and impaired wound healing in diabetic patients, an oil/water emulsion-based nano-ointment integrating...
Addressing the intertwined challenges of antimicrobial resistance and impaired wound healing in diabetic patients, an oil/water emulsion-based nano-ointment integrating phenylpropanoids-Eugenol and Cinnamaldehyde-with positively-charged silver nanoparticles was synthesized. The process began with the synthesis and characterization of nano-silver, aimed at ensuring the effectiveness and safety of the nanoparticles in biological applications. Subsequent experiments determined the minimum inhibitory concentration (MIC) against pathogens such as Streptococcus aureus, Pseudomonas aeruginosa and Candida albicans. These MIC values of all three active leads guided the strategic formulation of an ointment base, which effectively integrated the bioactive components. Evaluations of this nano-ointment revealed enhanced antimicrobial activity against both clinical and reference bacterial strains and it maintained stability after freeze-thaw cycles. Furthermore, the ointment demonstrated superior in-vitro diabetic wound healing capabilities and significantly promoted angiogenesis, as shown by enhanced blood vessel formation in the Chorioallantoic Membrane assay. These findings underscore the formulation's therapeutic potential, marking a significant advance in the use of nanotechnology for topical wound care.
Topics: Silver; Wound Healing; Microbial Sensitivity Tests; Metal Nanoparticles; Animals; Ointments; Acrolein; Candida albicans; Anti-Infective Agents; Pseudomonas aeruginosa; Administration, Topical; Humans; Anti-Bacterial Agents; Staphylococcus aureus
PubMed: 38862870
DOI: 10.1208/s12248-024-00936-4 -
Journal of Controlled Release :... Jul 2024The efficacy of DNA-damaging agents, such as the topoisomerase I inhibitor SN38, is often compromised by the robust DNA repair mechanisms in tumor cells, notably...
The efficacy of DNA-damaging agents, such as the topoisomerase I inhibitor SN38, is often compromised by the robust DNA repair mechanisms in tumor cells, notably homologous recombination (HR) repair. Addressing this challenge, we introduce a novel nano-strategy utilizing binary tumor-killing mechanisms to enhance the therapeutic impact of DNA damage and mitochondrial dysfunction in cancer treatment. Our approach employs a synergistic drug pair comprising SN38 and the BET inhibitor JQ-1. We synthesized two prodrugs by conjugating linoleic acid (LA) to SN38 and JQ-1 via a cinnamaldehyde thioacetal (CT) bond, facilitating co-delivery. These prodrugs co-assemble into a nanostructure, referred to as SJNP, in an optimal synergistic ratio. SJNP was validated for its efficacy at both the cellular and tissue levels, where it primarily disrupts the transcription factor protein BRD4. This disruption leads to downregulation of BRCA1 and RAD51, impairing the HR process and exacerbating DNA damage. Additionally, SJNP releases cinnamaldehyde (CA) upon CT linkage cleavage, elevating intracellular ROS levels in a self-amplifying manner and inducing ROS-mediated mitochondrial dysfunction. Our results indicate that SJNP effectively targets murine triple-negative breast cancer (TNBC) with minimal adverse toxicity, showcasing its potential as a formidable opponent in the fight against cancer.
Topics: Triple Negative Breast Neoplasms; Nanoparticles; Animals; Humans; Female; Cell Line, Tumor; Acrolein; Drug Delivery Systems; Camptothecin; Prodrugs; Linoleic Acid; Triazoles; DNA Damage; Antineoplastic Agents; Mice, Nude; Mice; Cell Cycle Proteins; Transcription Factors; Topoisomerase I Inhibitors; Bromodomain Containing Proteins; Azepines
PubMed: 38849089
DOI: 10.1016/j.jconrel.2024.06.012 -
Analytical Chemistry Jun 2024Ferroptosis is a pattern of cell death caused by iron-dependent accumulation of lipid peroxides and is closely associated with the occurrence and development of multiple...
Ferroptosis is a pattern of cell death caused by iron-dependent accumulation of lipid peroxides and is closely associated with the occurrence and development of multiple diseases. Acrolein (ACR), one of the final metabolites of lipid peroxidation, is a reactive carbonyl species with strong biotoxicity. Effective detection of ACR is important for understanding its role in the progression of ferroptosis and studying the specific mechanisms of ferroptosis-mediated diseases. However, visualization detection of ACR during ferroptosis has not yet been reported. In this work, the first ratiometric fluorescent probe () based on 2-(2'-hydroxyphenyl) benzothiazole (HBT) was designed for tracing endogenous ACR with an unprecedented regiospecific ACR-induced intramolecular cyclization strategy, which employs 2-aminoethanethiol as an ACR-selective recognition receptor. The experimental results showed that has excellent selectivity, high sensitivity (LOD = 0.26 μM) and good biocompatibility. More importantly, the upregulation of ACR levels was observed during ferroptosis in HeLa cells and zebrafish, indicating that ACR may be a specific active molecule that plays an essential biological role during ferroptosis or may serve as a potential marker of ferroptosis, which has great significance for studying the pathological process and treatment options of ferroptosis-related diseases.
Topics: Ferroptosis; Acrolein; Fluorescent Dyes; Humans; HeLa Cells; Zebrafish; Animals; Up-Regulation; Optical Imaging; Molecular Structure
PubMed: 38847602
DOI: 10.1021/acs.analchem.4c01690 -
Frontiers in Public Health 2024An increasing body of research has demonstrated a correlation between pollutants from the environment and the development of cardiovascular diseases (CVD). However, the...
INTRODUCTION
An increasing body of research has demonstrated a correlation between pollutants from the environment and the development of cardiovascular diseases (CVD). However, the impact of volatile organic chemicals (VOC) on CVD remains unknown and needs further investigation.
OBJECTIVES
This study assessed whether exposure to VOC was associated with CVD in the general population.
METHODS
A cross-sectional analysis was conducted utilizing data from five survey cycles (2005-2006, 2011-2012, 2013-2014, 2015-2016, and 2017-2018) of the National Health and Nutrition Examination Survey (NHANES) program. We analyzed the association between urinary VOC metabolites (VOCs) and participants by multiple logistic regression models, further Bayesian Kernel Machine Regression (BKMR) models and Weighted Quantile Sum (WQS) regression were performed for mixture exposure analysis.
RESULTS
Total VOCs were found to be positively linked with CVD in multivariable-adjusted models (p for trend = 0.025), independent of established CVD risk variables, such as hypertension, diabetes, drinking and smoking, and total cholesterol levels. Compared with the reference quartile of total VOCs levels, the multivariable-adjusted odds ratios in increasing quartiles were 1.01 [95% confidence interval (CI): 0.78-1.31], 1.26 (95% CI: 1.05-1.21) and 1.75 (95% CI: 1.36-1.64) for total CVD. Similar positive associations were found when considering individual VOCs, including AAMA, CEMA, CYMA, 2HPMA, 3HPMA, IPM3 and MHBMA3 (acrolein, acrylamide, acrylonitrile, propylene oxide, isoprene, and 1,3-butadiene). In BKMR analysis, the overall effect of a mixture is significantly related to VOCs when all chemicals reach or exceed the 75th percentile. Moreover, in the WQS models, the most influential VOCs were found to be CEMA (40.30%), DHBMA (21.00%), and AMCC (19.70%).
CONCLUSION
The results of our study indicated that VOC was all found to have a significant association with CVD when comparing results from different models. These findings hold significant potential for public health implications and offer valuable insights for future research directions.
Topics: Humans; Volatile Organic Compounds; Nutrition Surveys; Cardiovascular Diseases; Cross-Sectional Studies; Male; Female; Middle Aged; Adult; Environmental Exposure; Risk Factors; Air Pollutants; United States; Aged
PubMed: 38846604
DOI: 10.3389/fpubh.2024.1378444 -
Journal of Hazardous Materials Aug 2024We present a new method for investigating the oxidation and emission behavior of air-permeable materials. Employing this method, a differentiated statement can be made...
We present a new method for investigating the oxidation and emission behavior of air-permeable materials. Employing this method, a differentiated statement can be made about the extent to which critical volatile organic compounds (VOCs) such as formaldehyde, acetaldehyde, and acrolein are contained in the material as impurities or formed by thermo-oxidative degradation of the polymer matrix in the use phase. The parameters affecting methods of VOC analysis are reviewed and considered for the developed method. The molecular mechanisms of VOC formation are discussed. Toxicological implications of the reaction kinetics are put into context with international guidelines and threshold levels. This new method enables manufacturers of cellular materials not only to determine the oxidative stability of their products but also to optimize them specifically for higher durability. ENVIRONMENTAL IMPLICATION: Cellular materials are ubiquitous in the technosphere. They play a crucial role in various microenvironments such as automotive interiors, building insulation, and cushioning. These materials are susceptible to oxidative breakdown, leading to the release of formaldehyde, acetaldehyde, and acrolein. The ecotoxicological profiles of these compounds necessitate monitoring and regulation. The absence of reproducible and reliable analytical methods restricts research and development aimed at risk assessment and mitigation. This work significantly enhances the toolbox for optimizing the oxidative stability of any open-cell cellular material and evaluating these materials in terms of their temperature-dependent oxidation and emission behavior.
PubMed: 38843638
DOI: 10.1016/j.jhazmat.2024.134747 -
Journal of Agricultural and Food... Jun 2024Acrolein (ACR), methylglyoxal (MGO), and glyoxal (GO) are a class of reactive carbonyl species (RCS), which play a crucial role in the pathogenesis of chronic and...
Acrolein (ACR), methylglyoxal (MGO), and glyoxal (GO) are a class of reactive carbonyl species (RCS), which play a crucial role in the pathogenesis of chronic and age-related diseases. Here, we explored a new RCS inhibitor (theanine, THE) and investigated its capture capacity on RCS in by human experiments. After proving that theanine could efficiently capture ACR instead of MGO/GO by forming adducts under simulated physiological conditions, we further detected the ACR/MGO/GO adducts of theanine in the human urine samples after consumption of theanine capsules (200 and 400 mg) or green tea (4 cups, containing 200 mg of theanine) by using ultraperformance liquid chromatography-time-of-flight-high-resolution mass spectrometry. Quantitative assays revealed that THE-ACR, THE-2ACR-1, THE-MGO, and THE-GO were formed in a dose-dependent manner in the theanine capsule groups; the maximum value of the adducts of theanine was also tested. Furthermore, besides the RCS adducts of theanine, the RCS adducts of catechins could also be detected in the drinking tea group. Whereas, metabolite profile analysis showed that theanine could better capture RCS produced in the renal metabolic pathway than catechins. Our findings indicated that theanine could reduce RCS in the body in two ways: as a pure component or contained in tea leaves.
Topics: Humans; Tea; Glutamates; Male; Pyruvaldehyde; Glyoxal; Adult; Acrolein; Capsules; Camellia sinensis; Female; Young Adult; Plant Extracts; Chromatography, High Pressure Liquid
PubMed: 38825967
DOI: 10.1021/acs.jafc.4c02481 -
Phytomedicine : International Journal... Jul 2024Malassezia globosa is a commensal basidiomycetous yeast occurring on the skin that causes pityriasis versicolor (PV) and seborrheic dermatitis, but that has also been...
BACKGROUND
Malassezia globosa is a commensal basidiomycetous yeast occurring on the skin that causes pityriasis versicolor (PV) and seborrheic dermatitis, but that has also been implicated in other dermatoses. Cinnamaldehyde (CM) has antibacterial, antioxidant, and anti-inflammatory activities, but the effect of CM on M. globosa-infected PV has not been clarified.
PURPOSE
The study aimed to investigate the possible antifungal and antibiofilm activities of CM against M. globosa-infected PV in vivo and in vitro.
METHODS
The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of CM against M. globosa. The crystal violet staining assay and XTT assay were used to investigate the inhibition of CM on biofilm formation and the eradication of mature biofilms. The visualizations of the biofilm and cell distribution in the biofilm matrix were performed with a scanning electron microscope and confocal laser scanning microscope. The kits of antioxidant kinase were used to determine the activities of oxidative stress markers in M. globosa-stimulated HaCaT cells. Western blot assays were used to evaluate the role of TLR2/NF-κB in vitro. Furthermore, the protective effect of CM was assessed in M. globosa-associated PV mice. The expressions of inflammatory cytokines and apoptosis were screened using ELISA assays. The expressions of interleukin-6 and tumor necrosis factor-α were measured by an immunohistochemistry method in vivo.
RESULTS
Our results showed that the MIC of CM against planktonic cells of M. globosa was 4 µg/ml and treatment with 20 × MIC CM eradicated mature biofilms of M. globosa. In vitro, after CM treatment the levels of oxidative stress indicators (i.e., superoxide dismutase, catalase, glutathione) significantly increased, while the levels of malondialdehyde decreased. In addition, the expression of TLR2/NF-κB in HaCaT cells was significantly reduced after CM treatment. On the other hand, an in vivo therapeutic effect of CM was assessed against M. globosa-infected mice. The fungal load on the skin decreased after treatment with CM compared to the M. globosa-infected group. In addition, the uninfected animals showed a normal skin structure, whereas, the M. globosa-infected mice showed extensive infiltration of neutrophils in skin tissues that improved after treatment with CM. Meanwhile, the levels of inflammatory and apoptotic factors improved after CM treatment.
CONCLUSION
Our results showed that CM inhibits the biofilm formation of M. globosa and eradicates mature biofilms of M. globosa. Treatment with CM significantly decreased oxidative stress, apoptosis, and inflammatory markers in the skin tissue and HaCaT cells. Hence, this study suggests that CM is a good candidate therapeutic agent against M. globosa-induced PV infections because of its antifungal, antibiofilm, and anti-inflammatory properties.
Topics: Biofilms; Acrolein; Animals; Malassezia; Humans; Toll-Like Receptor 2; Tinea Versicolor; Antifungal Agents; Microbial Sensitivity Tests; Mice; Oxidative Stress; HaCaT Cells; NF-kappa B; Interleukin-6; Antioxidants; Tumor Necrosis Factor-alpha; Skin
PubMed: 38823343
DOI: 10.1016/j.phymed.2024.155542