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1.
Environ Int ; 158: 107000, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34991260

RESUMO

Per- and polyfluoroalkyl substances (PFAS) are widely detected environmental contaminants, and there is a great need for development of sensor technologies for rapid and continuous monitoring of PFAS. In this study, we have developed fluorescence based aptasensor that can possibly monitor perfluorooctanoic acid (PFOA) in water with limit of detection (LOD) of 0.17 µM. This is first to report the successful isolation of PFAS binding ssDNA aptamers. The obtained aptamer selectively binds PFOA with dissociation constant (KD) of 5.5 µM. Specific aptamer binding sites to PFOA were identified and the length of the fluorinated carbons was a key binding factor rather than the functional group. The aptamer binding to structurally similar PFAS compounds (i.e., perfluorocarboxylic acids and perfluorosulfonic acids with 4-8 carbon chains) was also investigated; the aptamer KD values were 6.5 and 3.3 µM for perfluoroheptanoic acid and perfluorohexanesulfonic acid, respectively, while other analogs did not bind to the aptamer. The presence of major inorganic ions and dissolved organic matter had negligible influences on the aptamer performance (<14% at a 10 mM concentration), and the aptamer performance was also robust in real wastewater effluent conditions, with a KD of 7.4 µM for PFOA. Fluorescence-based aptasensor developed in this study is adequate in monitoring PFOA levels in water contaminated with the accident spills and heavy usage of fire-fighting foams near the industrial sites and military bases. More importantly, the study opens up new capability of aptasensors to efficiently monitor the trace amount of various PFAS compounds and other fluorinated alternatives in natural and engineered water environments.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Poluentes Químicos da Água , Caprilatos , Fluorescência , Fluorcarbonetos/análise , Água , Poluentes Químicos da Água/análise
2.
J Hazard Mater ; 421: 126810, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34365231

RESUMO

The pollution of perfluorooctanoic acid (PFOA) in water bodies has been a serious threat to environment and human health. Ordered mesoporous carbons (OMCs) with different oxygen contents were prepared and first used for adsorbing PFOA from aqueous solutions. The OMC-900 with a lower oxygen content has a higher PFOA adsorption capacity than the oxygen-rich OMC-700. OMCs require a much shorter time to reach the adsorption equilibrium comparing with other adsorbents reported in literature. The mesopores play an important role in this rapid adsorption kinetics. The pseudo-second-order model better fitted the kinetic data. The multilayers adsorption was proposed for the adsorption of PFOA onto OMCs since the Freundlich isotherm model fits the experimental data well. The micelle or hemi-micelle structures may be formed during the adsorption. Various background salts showed a positive effect on PFOA adsorption due to the salting-out and divalent bridge effects. The humic acid can lead to a discernible reduction in PFOA adsorption by competing for adsorption sites on OMCs. The hydrophobic interaction and electrostatic interaction adsorption mechanisms were proposed and verified by the adsorption data. The high adsorption capacity and fast adsorption kinetics of the OMC make it a potential adsorbent for PFOA removal in engineering applications.


Assuntos
Carbono , Fluorcarbonetos , Adsorção , Caprilatos , Humanos , Cinética , Oxigênio
3.
Chemosphere ; 286(Pt 3): 131851, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34391114

RESUMO

Food consumption has been recognized as the most significant contributor to human exposure to polyfluoroalkyl and perfluoroalkyl substances (PFASs) for the general population. In 2020, EFSA introduced for the first time safety limit of 4.4 ng/kg body weight (bw) for weekly intake for the sum of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) which are all perfluoralkyl acids (PFAAs) that belong to PFASs group. Fish and eggs have been found to contribute significantly, almost 50 % to PFOS and PFOA dietary intake of the Greek population. In the present study, estimation of human intake of these four PFASs from fish, eggs and drinking water consumption is attempted. Data from EFSA food consumption database for fish and eggs are used for assessment. Mean weekly intake estimated is above the tolerable weekly intake (TWI) recently proposed, mainly due to fish consumption. Exceedance of the proposed TWI emphasizes the need for continuous monitoring of levels of PFASs in food in parallel with efforts to lower these levels.


Assuntos
Ácidos Alcanossulfônicos , Água Potável , Fluorcarbonetos , Ácidos Alcanossulfônicos/análise , Animais , Caprilatos/análise , Ovos , Fluorcarbonetos/análise , Grécia , Humanos , Ácidos Sulfônicos
4.
J Hazard Mater ; 422: 126953, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34449337

RESUMO

The discharge of widely used per- and poly-fluorinated compounds (PFCs) leads to their environmental prevalence, bioaccumulation and biotoxicity; and attracts researches focusing on their treatment in wastewater. Electrochemical reductive treatment is a promising alternative due to its milder reaction conditions and easy operation. The feasibility of electrochemical reductive decomposition of PFOA using a Rh/Ni cathode was explored. The Rh/Ni cathode was fabricated by coating Rh3+ on Ni foil through electrodeposition. The Rh coating was primarily elemental and in a Rh(111) crystalline form. PFOA decomposition and defluorination were observed when using the Rh/Ni cathode where DMF was the solvent and the cathode potential was -1.25 V. A hydrodefluorination reaction was considered having occurred. Because possessing d electrons and empty d orbitals, the Rh coating enhanced PFOA adsorption onto the cathode surface and facilitated CF bond activation through Rh···F interactions. Moreover, the Rh(111) crystal helped chemisorb the generated H* and supply it participating in PFOA decomposition. With the continuous interaction of cathode-supplied electrons, CF bond would ultimately dissociate and transform to CH bond by H* substitution. Adding FeCp2* as a supporting electrolyte enhanced PFOA decomposition by working as the shuttle facilitating PFOA migration to the cathode surface.


Assuntos
Caprilatos , Fluorcarbonetos , Adsorção , Eletrodos , Estudos de Viabilidade
5.
Sci Total Environ ; 805: 150326, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34543795

RESUMO

This study investigated the degradation of perfluorooctanoic acid (PFOA) on zerovalent iron-laden biochar (BC-ZVI) prepared by carbothermal reduction. Results show that over 99% PFOA can be removed by BC-ZVI in hydrothermal conditions under 240 °C within 6 h. The maximum defluorination rate of 63.2% was achieved after 192 h, and this outcome was significantly better than biochar (BC) and zero-valent iron (ZVI) alone. The short-chain perfluorinated compounds (PFCs) and perfluoroheptanal were detected in the liquid phase after degradation, suggesting that the degradation of PFOAs by BC-ZVI followed the Kobel decarboxylation process. XRD and SEM-EDS analyses strongly suggested that carbothermal reduction could avoid the agglomeration of ZVI loaded onto biochar, which helped make the PFOA degradation more efficient. The frontier molecular orbital theory calculated by density functional theory revealed there were two possibilities for ZVI loading on BC (edged or internal loading), while the edge loaded ZVI had a greater tendency to provide electrons for the defluorination of PFOA than internally loaded ZVI.


Assuntos
Ferro , Poluentes Químicos da Água , Caprilatos , Carvão Vegetal , Fluorcarbonetos , Poluentes Químicos da Água/análise
6.
Chemosphere ; 287(Pt 3): 132297, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34555580

RESUMO

Per-and polyfluoroalkyl substances (PFAS), a large class of synthesized chemicals, are persistent in nature and generally recalcitrant to conventional chemical and biological treatment. Adsorption is considered an economical and practical method for PFAS treatment. Layered double hydroxides (LDHs) represent a promising class of mineral-based adsorbents for PFAS removal because of the highly positive charge of their structural layers. In this research, the performance of two representative LDHs with varied cation compositions, namely Zn-Al and Mg-Al LDHs, were investigated and compared for the removal of perfluorinated carboxylic acids (PFCAs) with an emphasis on perfluorooctanoic acid (PFOA). Zn-Al LDH showed high efficiency for the removal of medium- and long-chain PFCAs (i.e., C ≥ 7), and performed consistently better than Mg-Al LDH. Based on detailed adsorption kinetics and isotherm studies toward PFOA, Zn-Al LDH showed higher adsorption capacity, stronger adsorption affinity, and faster kinetics than Mg-Al LDH. Presence of natural organic matter had minimal impact on PFOA removal by Zn-Al LDH, but sulfate severely inhibited PFOA adsorption. Combined results of aqueous adsorption experiments and sorbent characterization suggested that electrostatic interactions may be the primary mechanism for PFOA adsorption onto LDHs. Our results suggested that cation composition of LDHs can have significant effect on the performance for PFCA removal.


Assuntos
Fluorcarbonetos , Poluentes Químicos da Água , Adsorção , Caprilatos , Hidróxidos , Zinco
7.
Sci Total Environ ; 806(Pt 1): 150438, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34562763

RESUMO

To simulate the real cell status and morphology in the living systems is substantial for using cell models to address the detrimental effects of toxic contaminants. In this study, the comparative profiles of metabolites in three-dimensional (3D) human normal liver (L-02) cell spheroids with perfluorooctanoic acid (PFOA) treatment were analyzed using a metabolomic approach. The uniform 3D cell spheroids were well formed in 3 days (e.g., sphericity index >0.9) and stably maintained over the subsequent 11 days. The cytotoxicity of PFOA to the 3D L-02 cell spheroids was highly dependent on both exposure concentration and duration. Comparative analysis of metabolomes showed that the number of differential metabolites in the 3D cell spheroids treated with 300 µM PFOA for 10 days (n = 59) was greater than those with a 4-day exposure to 300 µM PFOA (n = 17). Six metabolic pathways related to amino acids metabolism were only found in the 3D cell spheroids with a 10-day treatment of 300 µM PFOA, which could not be found in the 2D monolayer cells and those 3D cell spheroids with a 4-day exposure. The suppression of PFOA on glutamine metabolism substantially decreased glutathione (GSH) production and accordingly increased the level of reactive oxygen species in the 3D cell spheroids. On the contrary, the supplementation of glutamine increased GSH production and the viability of cell spheroids, indicating that glutamine metabolism played a critical role in the chronic toxic effects of PFOA. Our study strongly suggested that comprehensive toxicological methodologies based on the 3D cell models could currently be robust and suitable for addressing the chronic adverse effects of toxic contaminants.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Fluorcarbonetos , Aminoácidos , Caprilatos/toxicidade , Técnicas de Cultura de Células , Fluorcarbonetos/toxicidade , Humanos , Metabolômica
8.
Chemosphere ; 287(Pt 3): 132205, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34563764

RESUMO

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have attracted attention due to their widespread distribution, recalcitrance, and substantial toxicity. In this work, high concentrations of PFOA and PFOS were degraded and mobilized through electrochemical treatments in a simulated source zone of saturated soil. Under a low constant voltage and direct current of 24 V and 467-690 mA, approximately 51.7% and 33% of PFOA and PFOS were degraded, respectively. Additionally, a total defluorination mass balance of 44.7% and 23% were detected for PFOA and PFOS, respectively, which indicates that the removal of PFOA and PFOS occurs through its destruction. Substantial electromigration causes the destruction and mobilization of solid PFOA and PFOS to shift into the water phase. Although electrochemical oxidation of PFAS (per- and polyfluoroalkyl substances) were previously reported and studied, this study is one of the few that focus on simultaneous desorption, mobilization, and destruction of PFAS in saturated soil containing a low-intensity electrical field.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Caprilatos , Fluorcarbonetos/análise , Solo
9.
Chemosphere ; 287(Pt 1): 132064, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34474389

RESUMO

The occurrence, spatial distribution, potential sources, and risk assessment of 14 perfluoroalkyl acids (PFAAs), including 11 perfluoroalkyl carboxylic acids and 3 perfluoroalkyl sulfonates acids, were investigated in 21 drinking water sources from the lower Yangtze River in November 2019. The total PFAAs (∑PFAAs) concentrations ranged from 39.3 to 220.3 ng/L, and perfluorooctanoic acid and perfluorooctanesulfonate were predominant with average concentrations of 19.4 and 15.4 ng/L, respectively. The higher ∑PFAAs concentrations in the southern shore and downstream could be attributed to industrial development and surface runoff/tide currents, respectively. Principal component analysis-multiple linear regression revealed that the primary sources of PFAAs were fluororesin coatings/metal plating, surface runoff/textile, effluent discharge/food packaging, and leather/fabrics. Human intake risks of PFAAs were assessed by target hazard quotient (THQ), which showed that human health risks of PFAAs decreased with increasing age, excluding 13-17 years age group. Moreover, the total exposure risks of PFOA/PFOS in all sampling sites to people aged over 18 years calculated based on contribution from drinking water were noted to be at safe level. The results obtained were helpful for improving our understanding of human health risks of PFAAs, and expanding our knowledge on PFAAs in drinking water.


Assuntos
Ácidos Alcanossulfônicos , Água Potável , Fluorcarbonetos , Poluentes Químicos da Água , Adolescente , Adulto , Ácidos Alcanossulfônicos/análise , Caprilatos/análise , China , Monitoramento Ambiental , Fluorcarbonetos/análise , Humanos , Pessoa de Meia-Idade , Medição de Risco , Poluentes Químicos da Água/análise
10.
Bioresour Technol ; 344(Pt A): 126161, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34678453

RESUMO

Using waste biomass to prepare various products by environmentally benign processes is a good way to practice green and sustainable development. In this paper, high porosity and surface area biomass activated carbon was obtained by pyrolysis of pine sawdust without using any chemicals after steam bursting pretreatment. Under hydrothermal conditions at 160 ℃, the differences of steam bursting at 300, 500, or 700 psi pressures on the structure and surface chemical groups of the final activated carbons product were compared. The characterization showed that the specific surface areas and micropore volumes decreased with the increase of pressure, while the relative content of oxygen-containing functional groups changed slightly. The sample obtained following 300 psi pretreatment (HPB300) offered the highest BET surface area and pore volume, 962 m2/g and 0.526 cm3/g respectively, and which also achieved the highest adsorption amounts for both methylene blue (MB) and perfluorooctanoic acid (PFOA).


Assuntos
Carvão Vegetal , Azul de Metileno , Adsorção , Biomassa , Caprilatos , Fluorcarbonetos , Porosidade , Vapor
11.
Chemosphere ; 287(Pt 3): 132170, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34826932

RESUMO

Perfluorooctanoic acid (PFOA), a hazardous environmental pollutant, has been found to enhance hepatic synthesis of fibroblast growth factor 21 (FGF21). FGF21 can enter the brain and increase the expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN). In this study, adult male mice were orally administered PFOA to evaluate how it regulates emotion. Exposure of mice to PFOA (1 mg kg-1 bw) for 10 consecutive days (PFOA-mice) caused anxiety-like behaviors and a peroxisome proliferator-activated receptor α (PPARα)-dependent increase in hepatic FGF21 synthesis. The levels of CRF expression in not only PVN but also basolateral amygdala complex (BLA) neurons of PFOA-mice were increased via FGF receptor 1 (FGF-R1) activation. However, the microinjection of FGF-R1 or CRF 1 receptor (CRF-R1) antagonist in the BLA rather than the PVN of PFOA-mice could relieve their anxiety-like behaviors. In addition, external capsule-BLA synaptic transmission in PFOA-mice was enhanced by increasing CRF-R1-mediated presynaptic glutamate release, which was corrected by the blockade of PPARα, FGF-R1 and CRF-R1 or the inhibition of PKA. Furthermore, the threshold of frequency-dependent long-term potentiation (LTP) induction was decreased in the BLA of PFOA-mice, which depended on the activation of PPARα, FGF-R1, CRF-R1, PKA and NMDA receptor (NMDAR), whereas long-term depression (LTD) induction was unchanged. Thus, the results indicate that the exposure of male mice to PFOA (1 mg kg-1 bw) enhances CRF expression in BLA neurons by increasing hepatic FGF21 synthesis, which then enhances CRF-R1-mediated presynaptic glutamate release to facilitate NMDAR-dependent BLA-LTP induction, leading to the production of anxiety-like behaviors.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Hormônio Liberador da Corticotropina , Animais , Ansiedade/induzido quimicamente , Complexo Nuclear Basolateral da Amígdala/metabolismo , Caprilatos/toxicidade , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Fluorcarbonetos , Masculino , Camundongos
12.
Environ Res ; 204(Pt A): 111995, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34492278

RESUMO

Due to the potential hazard of perfluorooctanoic acid (PFOA), hexafluoropropylene oxide dimer acid (HFPO-DA, GenX) has become a typical alternative since 2009. However, GenX has recently been reported to have equal or even greater toxicity and bioaccumulation than PFOA. Considering the suitability of alternatives, it is quite essential to study and compare the degradation degree between PFOA and GenX in water. Therefore, in the present study, a comprehensive degradation comparison between them via electrooxidation with a titanium suboxide membrane anode was conducted. The degradation rate decreased throughout for PFOA, while it first increased and then decreased for GenX when the permeate flux increased from 17.3 L to 100.3 L m-2·h-1. The different responses of PFOA and GenX to flux might be attributed to their different solubilities. In addition, the higher kobs of PFOA demonstrated that it had a better degradability than GenX by 2.4-fold in a mixed solution. The fluorinated byproduct perfluoropropanoic acid (PFPrA) was detected as a GenX intermediate, suggesting that ether bridge splitting was needed for GenX electrooxidation. This study provides a reference for assessing the degradability of GenX and PFOA and indicates that it is worth reconsidering whether GenX is a suitable alternative for PFOA from the point of view of environmental protection.


Assuntos
Fluorcarbonetos , Poluentes Químicos da Água , Bioacumulação , Caprilatos , Fluorcarbonetos/análise , Poluentes Químicos da Água/análise
13.
Int J Mol Sci ; 22(24)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34948360

RESUMO

S100B is an astrocytic protein behaving at high concentration as a damage-associated molecular pattern molecule. A direct correlation between the increased amount of S100B and inflammatory processes has been demonstrated, and in particular, the inhibitor of S100B activity pentamidine has been shown to ameliorate clinical scores and neuropathologic-biomolecular parameters in the relapsing-remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. This study investigates the effect of arundic acid (AA), a known inhibitor of astrocytic S100B synthesis, in the chronic experimental autoimmune encephalomyelitis, which is another mouse model of multiple sclerosis usually studied. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the spinal cord, we observed that the AA-treated group showed lower severity compared to the vehicle-treated mice, particularly in the early phase of disease onset. We also observed a significant reduction of astrocytosis, demyelination, immune infiltrates, proinflammatory cytokines expression and enzymatic oxidative reactivity in the AA-treated group. Overall, our results reinforce the involvement of S100B in the development of animal models of multiple sclerosis and propose AA targeting the S100B protein as a focused potential drug to be considered for multiple sclerosis treatment.


Assuntos
Caprilatos/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Subunidade beta da Proteína Ligante de Cálcio S100/antagonistas & inibidores , Animais , Caprilatos/farmacologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Terapia de Alvo Molecular , Esclerose Múltipla/metabolismo , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo
14.
Ying Yong Sheng Tai Xue Bao ; 32(11): 4147-4155, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34898131

RESUMO

Perfluorooctanoic acid (PFOA) is an important perfluorinated surfactant, which has received great attention as an emerging pollutant, due to its persistence, high toxicity, and bioaccumulation. Sediment is an important environmental reservoir for PFOA, while polluted sediment can serve as a long-term contamination source causing pollution to overlying surface water and surrounding groundwater. Here, the source, pollution level, adsorption and transport of PFOA at the sediment-water interface were systematically reviewed. Industrial discharge was the major release for PFOA entering surface water and sediment. PFOA was generally at ng·L-1 and ng·g-1 levels in global surface water and sediment. More serious pollution was found in some parts of China. Sediment composition, hadrochemical condition, natural organic matter, and surfactants could strongly affect PFOA adsorption in sediment, though the controlling mechanisms were controversial. Research on PFOA transport in sediment had just been started with limited progress. There is a great gap in understanding the mechanisms underlying PFOA transport in sediment, which should be strengthened in the future.


Assuntos
Fluorcarbonetos , Água , Adsorção , Caprilatos
15.
Artigo em Inglês | MEDLINE | ID: mdl-34948492

RESUMO

BACKGROUND: Residents of a large area of north-eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Despite the large amount of evidence in adults of a positive association between serum PFAS and metabolic outcomes, studies focusing on children and adolescents are limited. We evaluated the associations between serum PFAS concentrations that were quantifiable in at least 40% of samples and lipid profile, blood pressure (BP) and body mass index (BMI) in highly exposed adolescents and children. METHODS: A cross-sectional analysis was conducted in 6669 adolescents (14-19 years) and 2693 children (8-11 years) enrolled in the health surveillance program of the Veneto Region. Non-fasting blood samples were obtained and analyzed for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated. Systolic and diastolic BP were measured, and BMI z-score accounting for age and sex was estimated. The associations between ln-transformed PFAS (and categorized into quartiles) and continuous outcomes were assessed using generalized additive models. The weighted quantile sum regression approach was used to assess PFAS-mixture effects for each outcome. Analyses were stratified by gender and adjusted for potential confounders. RESULTS: Among adolescents, significant associations were detected between all investigated PFAS and TC, LDL-C, and to a lesser extent HDL-C. Among children, PFOS and PFNA had significant associations with TC, LDL-C and HDL-C, while PFOA and PFHxS had significant associations with HDL-C only. Higher serum concentrations of PFAS, particularly PFOS, were associated with lower BMI z-score. No statistically significant associations were observed between PFAS concentrations and BP. These results were confirmed by the multi-pollutant analysis. CONCLUSIONS: Our study supports a consistent association between PFAS concentration and serum lipids, stronger for PFOS and PFNA and with a greater magnitude among children compared to adolescents, and a negative association of PFAS with BMI.


Assuntos
Ácidos Alcanossulfônicos , Doenças Cardiovasculares , Água Potável , Poluentes Ambientais , Fluorcarbonetos , Adolescente , Adulto , Caprilatos , Criança , Estudos Transversais , Humanos
17.
Int J Mol Sci ; 22(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34639049

RESUMO

The ability of sodium caprylate and l-menthol to fluidize phospholipid bilayers composed of lipids simulating the buccal epithelium was investigated using electron spin resonance (ESR) to evaluate the action of these agents as permeation enhancers. 5-Doxyl stearic acid (5-DSA) and 16-doxyl stearic acid (16-DSA) were used as spin labels to identify alterations in membrane fluidity near the polar head groups or inner acyl regions of the lipid bilayer, respectively. The molecular motion of both 5-DSA and 16-DSA showed increased disorder near the polar and inner hydrophobic regions of the bilayer in the presence of sodium caprylate suggesting fluidization in both the regions, which contributes to its permeation enhancing effects. L-menthol decreased the order parameter for 16-DSA, showing membrane fluidization only in the inner acyl regions of the bilayer, which also corresponded to its weaker permeation enhancing effects. The rapid evaluation of changes in fluidity of the bilayer in the presence of potential permeation enhancers using ESR enables improved selection of effective permeation enhancers and enhancer combinations based on their effect on membrane fluidization.


Assuntos
Caprilatos/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica , Fluidez de Membrana/efeitos dos fármacos , Mentol/farmacologia , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Óxidos N-Cíclicos/química , Óxidos N-Cíclicos/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Bicamadas Lipídicas , Lipossomos , Lipídeos de Membrana/química , Lipídeos de Membrana/metabolismo , Fosfolipídeos/química , Fosfolipídeos/metabolismo
18.
Int J Mol Sci ; 22(19)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34639130

RESUMO

Metabolic transformation of cancer cells leads to the accumulation of lactate and significant acidification in the tumor microenvironment. Both lactate and acidosis have a well-documented impact on cancer progression and negative patient prognosis. Here, we report that cancer cells adapted to acidosis are significantly more sensitive to oxidative damage induced by hydrogen peroxide, high-dose ascorbate, and photodynamic therapy. Higher lactate concentrations abrogate the sensitization. Mechanistically, acidosis leads to a drop in antioxidant capacity caused by a compromised supply of nicotinamide adenine dinucleotide phosphate (NADPH) derived from glucose metabolism. However, lactate metabolism in the Krebs cycle restores NADPH supply and antioxidant capacity. CPI-613 (devimistat), an anticancer drug candidate, selectively eradicates the cells adapted to acidosis through inhibition of the Krebs cycle and induction of oxidative stress while completely abrogating the protective effect of lactate. Simultaneous cell treatment with tetracycline, an inhibitor of the mitochondrial proteosynthesis, further enhances the cytotoxic effect of CPI-613 under acidosis and in tumor spheroids. While there have been numerous attempts to treat cancer by neutralizing the pH of the tumor microenvironment, we alternatively suggest considering tumor acidosis as the Achilles' heel of cancer as it enables selective therapeutic induction of lethal oxidative stress.


Assuntos
Acidose/fisiopatologia , Caprilatos/farmacologia , Ciclo do Ácido Cítrico/efeitos dos fármacos , Glucose/metabolismo , Mitocôndrias/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Sulfetos/farmacologia , Microambiente Tumoral , Adaptação Fisiológica , Antineoplásicos/farmacologia , Metabolismo Energético , Glicólise , Humanos , Concentração de Íons de Hidrogênio , Ácido Láctico/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo , Células Tumorais Cultivadas
19.
Water Res ; 205: 117683, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34607087

RESUMO

Hexafluoropropylene oxide dimer acid (GenX) has been marketed as a substitute for perfluorooctanoic acid (PFOA) to reduce environmental and health risks. GenX and PFOA have been detected in various natural water sources, and adsorption is recognized as a typical treatment process for PFOA removal. In this paper, comparisons of GenX and PFOA adsorption are evaluated, including adsorption potential, adsorption mechanisms, and associated costs. A detailed literature review suggests that anion-exchange resins are more effective in removing GenX than activated carbon. GenX removal efficiency through activated carbon (30%) is lower than that of PFOA (80-95%), while GenX and PFOA removal efficiencies by anion exchange resins are similar (99%). Unconventional adsorbents, such as ionic fluorogels and covalent organic frameworks can effectively remove GenX from water. The review reveals that GenX adsorption is more challenging, requiring almost 4 times the treatment cost of its predecessor, PFOA. Annual operation and maintenance costs for GenX adsorption (initial concentration of GenX and PFOA = 0.2 µg.L-1) by GAC for treating 10,000 m3 per day is almost US$1,000,000 per year, but only around US$240,000 per year for PFOA. Desorption of GenX in the presence of PFOA highlights GenX's inferior treatability by adsorption. It is believed that GenX is a more environmentally friendly compound than PFOA, but this environmental friendliness comes with the price.


Assuntos
Fluorcarbonetos , Poluentes Químicos da Água , Adsorção , Caprilatos , Fluorcarbonetos/análise , Água , Poluentes Químicos da Água/análise
20.
J Immunol Methods ; 499: 113164, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34624302

RESUMO

BACKGROUND: Human rabies immunoglobulin (RIG) is an integral part of post-exposure prophylactic treatment of rabies (along with rabies vaccination). Infiltration of most, if not all, of the RIG dose at the wound site is recommended. RIG produced by a caprylate/chromatography manufacturing process (RIG-C; HyperRAB) increased the potency and purity of this product over the existing licensed RIG from a solvent/detergent process (RIG-S/D; HyperRAB-S/D). METHODS: A series of studies were conducted to characterize the content and purity of RIG-C. A single-dose pharmacokinetic study in rabbits was performed to compare intramuscular (IM) immunoglobulin products manufactured by two different purification processes, solvent/detergent (IGIM-S/D) and caprylate/chromatography (IGIM-C). RESULTS: RIG-C was found to be a highly purified IgG formulation with high monomer content and formulated with twice the anti-rabies potency of RIG-S/D while maintaining the same overall protein concentration. RIG-C facilitates IM administration at the wound site by halving the injection volume. The new caprylate/chromatography process eliminated detectible levels of pro-coagulant impurities and IgA that were carried through in the prior S/D process. These impurities have been associated with thrombotic complications and allergic reactions in susceptible patients. After single dose administration, IGIM-C was pharmacokinetically equivalent to IGIM-S/D in rabbits. CONCLUSION: RIG-C is a more potent RIG formulation with less impurities yielding a safer and more convenient product with similar pharmacokinetic profile.


Assuntos
Caprilatos/química , Globulinas/análise , Cromatografia , Globulinas/imunologia , Humanos , Vírus da Raiva/imunologia
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