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Environmental Health Perspectives Apr 2020Per- and polyfluoroalkyl substances (PFAS) are a diverse class of industrial chemicals with widespread environmental occurrence. Exposure to long-chain PFAS is...
BACKGROUND
Per- and polyfluoroalkyl substances (PFAS) are a diverse class of industrial chemicals with widespread environmental occurrence. Exposure to long-chain PFAS is associated with developmental toxicity, prompting their replacement with short-chain and fluoroether compounds. There is growing public concern over the safety of replacement PFAS.
OBJECTIVE
We aimed to group PFAS based on shared toxicity phenotypes.
METHODS
Zebrafish were developmentally exposed to 4,8-dioxa-3H-perfluorononanoate (ADONA), perfluoro-2-propoxypropanoic acid (GenX Free Acid), perfluoro-3,6-dioxa-4-methyl-7-octene-1-sulfonic acid (PFESA1), perfluorohexanesulfonic acid (PFHxS), perfluorohexanoic acid (PFHxA), perfluoro--octanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), or 0.4% dimethyl sulfoxide (DMSO) daily from 0-5 d post fertilization (dpf). At 6 dpf, developmental toxicity and developmental neurotoxicity assays were performed, and targeted analytical chemistry was used to measure media and tissue doses. To test whether aliphatic sulfonic acid PFAS cause the same toxicity phenotypes, perfluorobutanesulfonic acid (PFBS; 4-carbon), perfluoropentanesulfonic acid (PFPeS; 5-carbon), PFHxS (6-carbon), perfluoroheptanesulfonic acid (PFHpS; 7-carbon), and PFOS (8-carbon) were evaluated.
RESULTS
PFHxS or PFOS exposure caused failed swim bladder inflation, abnormal ventroflexion of the tail, and hyperactivity at nonteratogenic concentrations. Exposure to PFHxA resulted in a unique hyperactivity signature. ADONA, PFESA1, or PFOA exposure resulted in detectable levels of parent compound in larval tissue but yielded negative toxicity results. GenX was unstable in DMSO, but stable and negative for toxicity when diluted in deionized water. Exposure to PFPeS, PFHxS, PFHpS, or PFOS resulted in a shared toxicity phenotype characterized by body axis and swim bladder defects and hyperactivity.
CONCLUSIONS
All emerging fluoroether PFAS tested were negative for evaluated outcomes. Two unique toxicity signatures were identified arising from structurally dissimilar PFAS. Among sulfonic acid aliphatic PFAS, chemical potencies were correlated with increasing carbon chain length for developmental neurotoxicity, but not developmental toxicity. This study identified relationships between chemical structures and phenotypes that may arise from shared mechanisms of PFAS toxicity. These data suggest that developmental neurotoxicity is an important end point to consider for this class of widely occurring environmental chemicals. https://doi.org/10.1289/EHP5843.
Topics: Animals; Dose-Response Relationship, Drug; Fluorocarbons; Neurotoxins; Propionates; Tissue Distribution; Water Pollutants, Chemical; Zebrafish
PubMed: 32271623
DOI: 10.1289/EHP5843 -
Frontiers in Nutrition 2021Medium-chain triacylglycerides (MCTs) are dietary supplements that can induce ketosis without the need for a traditional ketogenic diet or prolonged fasting. They have... (Review)
Review
Medium-chain triacylglycerides (MCTs) are dietary supplements that can induce ketosis without the need for a traditional ketogenic diet or prolonged fasting. They have the potential to marginally delay the progression of neurodegenerative diseases, such as Alzheimer's disease. However, there have been inconsistencies in reports of the MCT dose-response relationship, which may be due to differences in MCT composition, participant characteristics, and other factors that can influence ketone generation. To resolve these discrepancies, we reviewed studies that investigated the ketogenic effect of MCTs in healthy adults. Aside from the treatment dose, other factors that can influence the ketogenic response, such as accompanying meals, fasting duration, and caffeine intake, were assessed. Based on the available literature, four practical recommendations are made to optimize the ketogenic effect of MCTs and reduce unwanted side effects (primarily gastrointestinal discomfort and diarrhea). First, the starting dose should be either 5 g of octanoic acid [caprylic acid (C8); a component of MCTs] or 5 g of a combination of C8 and decanoic or capric acid (C10; another component of MCTs), and the dose should be progressively increased to 15-20 g of C8. Second, MCTs should be consumed after an overnight fast, without an accompanying meal if tolerable, or with a low-carbohydrate meal. Third, the addition of caffeine may slightly increase the ketogenic response. Fourth, emulsifying the MCTs might increase their ketogenic effect and alleviate side effects.
PubMed: 34888335
DOI: 10.3389/fnut.2021.747284 -
New Solutions : a Journal of... Aug 2015Perfluorinated alkyl substances have been in use for over sixty years. These highly stable substances were at first thought to be virtually inert and of low toxicity.... (Review)
Review
Perfluorinated alkyl substances have been in use for over sixty years. These highly stable substances were at first thought to be virtually inert and of low toxicity. Toxicity information slowly emerged on perfluorooctanoic acid and perfluorooctane sulfonate. More than thirty years ago, early studies reported immunotoxicity and carcinogenicity effects. The substances were discovered in blood samples from exposed workers, then in the general population and in community water supplies near U.S. manufacturing plants. Only recently has research publication on perfluorooctanoic acid and perfluorooctane sulfonate intensified. While the toxicology database is still far from complete, carcinogenicity and immunotoxicity now appear to be relevant risks at prevalent exposure levels. Existing drinking water limits are based on less complete evidence that was available before 2008 and may be more than 100-fold too high. As risk evaluations assume that untested effects do not require regulatory attention, the greatly underestimated health risks from perfluorooctanoic acid and perfluorooctane sulfonate illustrate the public health implications of assuming the safety of incompletely tested industrial chemicals.
Topics: Alkanesulfonic Acids; Animals; Caprylates; Carcinogenicity Tests; Environmental Monitoring; Environmental Pollutants; Environmental Pollution; Female; Fluorocarbons; Healthy Worker Effect; Humans; Male; Maximum Allowable Concentration; Risk Assessment
PubMed: 26084549
DOI: 10.1177/1048291115590506 -
Biofilm Dec 2023Antibiotic therapy is the primary treatment for bovine mastitis, but the drawbacks of this strategy include poor cure rate and economic losses from the need to discard...
Antibiotic therapy is the primary treatment for bovine mastitis, but the drawbacks of this strategy include poor cure rate and economic losses from the need to discard milk with antibiotic residues. Unfortunately, few other treatment options are currently available for mastitis. Failure of antibiotic treatments is often attributed to formation of bacterial biofilms and abscesses in the mammary gland tissue, which lead to chronic infections that are difficult to eradicate and drive recurrent disease. A major mastitis-causing pathogen (MCP) associated with biofilms in bovine mastitis is . In this study, we demonstrate that octanoic acid has broad-spectrum microbicidal activity against MCPs and effectively inhibits biofilm formation in milk (>50% inhibition at 3.13 mM). Octanoic acid effectively clears biofilms (95% eradication at 1 minimum bactericidal concentration, MBC) and infrequently induces small colony variants (SCVs) that may cause recurrent mastitis. Additionally, octanoic acid rapidly kills persistent biofilm cells and cells with antibiotic tolerance (within 4 h). In contrast, antibiotics treated at >100 MBC cannot eradicate biofilms but do induce SCVs and antibiotic-tolerant cells. These effects may accelerate the transition from biofilm to chronic infection. Thus, octanoic acid exhibits bactericidal action against biofilms, and it is less likely than antibiotic therapy to induce persistent cells and pathogen tolerance. Moreover, octanoic acid acts additively with antibiotics against , and it attenuates tetracycline-induced virulence factor gene expression in cells. According to these data, octanoic acid may prevent the pathological progression of bovine mastitis and offer a new strategy for treating the condition.
PubMed: 37635811
DOI: 10.1016/j.bioflm.2023.100149 -
Nutrients Jun 2022Background: Medium Chain Fatty Acids (MCFAs) are a dietary supplement that exhibit interesting properties, due to their smaller molecular size. The acute consumption of...
Background: Medium Chain Fatty Acids (MCFAs) are a dietary supplement that exhibit interesting properties, due to their smaller molecular size. The acute consumption of MCFAs is expected to enhance exercise performance. However, the short-term effects of MCFAs on endurance performance remains poorly understood. The aim of our study is to evaluate the octanoic acid (C8)-rich diet effect on endurance capacity, and to explore their molecular and cellular effects. Methods: C57BL/6J mice were fed with a chow diet (Control group) or an octanoic acid-rich diet (C8 diet) for 6 weeks. Spontaneous activity, submaximal and maximal exercise tests were carried out to characterize the exercise capacities of the mice. Beta-oxidation and mitochondrial biogenesis pathways were explored in skeletal muscle by RT-qPCR, Western Blot (Quadriceps) and histochemical staining (Gastrocnemius). Results: Mice fed with a C8-rich diet presented a higher spontaneous activity (p < 0.05) and endurance capacities (p < 0.05) than the control, but no effect on maximal effort was observed. They also presented changes in the skeletal muscle metabolic phenotype, with a higher number of the oxidative fibers, rich in mitochondria. At the molecular level, the C8-diet induced an AMPK activation (p < 0.05), associated with a significant increase in PGC1a and CS gene expression and protein levels. Conclusion: Our study provided evidence that C8-enrichment as a food supplementation improves endurance capacities and activates mitochondrial biogenesis pathways leading to higher skeletal muscle oxidative capacities.
Topics: Animals; Caprylates; Diet, High-Fat; Fatty Acids; Mice; Mice, Inbred C57BL; Mitochondria, Muscle; Muscle, Skeletal; Organelle Biogenesis; Physical Conditioning, Animal; Physical Endurance
PubMed: 35807901
DOI: 10.3390/nu14132721 -
Pathogens (Basel, Switzerland) Jan 2022This study aims to investigate six food additives (octanoic acid, decanoic acid, acesulfame K, aspartame, saccharin, and sucralose) used in foods for the elderly or...
This study aims to investigate six food additives (octanoic acid, decanoic acid, acesulfame K, aspartame, saccharin, and sucralose) used in foods for the elderly or people with dysphagia because of the effect of these food additives on (), which is a keystone pathogen of periodontal diseases. The growth of was inhibited by 5 mM octanoic acid, 1.25 mM decanoic acid, 1.25% acesulfame K, 0.0625% aspartame, 0.03125% saccharin, and 0.625% sucralose. In addition, these food additives showed bactericidal activity for planktonic (5 mM octanoic acid, 5 mM decanoic acid, 0.25% aspartame, 0.25% saccharin, and 5% sucralose). Moreover, biofilm formation was inhibited by 10 mM octanoic acid, 10 mM decanoic acid, 10% acesulfame K, 0.35% aspartame, 0.5% saccharin, and 7.5% sucralose. Moreover, the same concentration of these food additives without aspartame killed in the biofilm. Aspartame and sucralose did not show cytotoxicity to human cell lines at concentrations that affected These findings may be useful in clarifying the effects of food additives on periodontopathogenic bacteria.
PubMed: 35056013
DOI: 10.3390/pathogens11010065 -
Nutrition & Metabolism 2020Marathon, as a long-distance aerobic exercise, has become a fashionable or popular sport. However, little is known about the holistic metabolic changes occurring within...
INTRODUCTION
Marathon, as a long-distance aerobic exercise, has become a fashionable or popular sport. However, little is known about the holistic metabolic changes occurring within the serum metabolome of athletes after the completion of a marathon.
OBJECTIVES
The goal of current study was to have an in-depth understanding of the impact of marathon on human metabolomics as well as the relationships among a variety of metabolites.
METHODS
The 20 studied subjects were all adult males who participated in a marathon. The serum samples of these participants were collected before and after the marathon and the biochemical metabolites in the serum were identified by an untargeted two-dimensional gas chromatography time-of-flight mass spectrometry.
RESULTS
All participants completed the marathon within 3 h. Compared to those before exercise, serum urea and creatine kinase, as well as cortisol, elevated significantly ( < 0.05), whereas testosterone decreased significantly ( < 0.01). Metabolomic analysis showed that, compared to those before the competition, metabolites pyruvic acid, glyceric acid, malic acid, cis-aconitic acid, galacturonic acid, methyl fumaric acid, maltotriose, and others increased significantly after the competition ( < 0.05), but glucosamine and O-succinyl-L-homoserine decreased significantly ( < 0.05). Amino acid indexes, such as alanine, L-tyrosine and phenylalanine, increased significantly after exercise compared with those before exercise ( < 0.05), whereas serine, valine and asparagine decreased significantly ( < 0.05). Lipid metabolism indexes, glycerol, glyceric acid, octanoic acid, and quinic acid increased significantly ( < 0.05). Theophylline, xanthine and other indicators of caffeine metabolism increased significantly ( < 0.05). Furthermore, marathon performance, fat percentage, VOmax, and hemoglobin were correlated with the serum metabonomic indicators, so were serum testosterone and cortisol.
CONCLUSION
These results illustrate that the metabolism of glucose and lipid of the athletes was enhanced following the marathon match. In addition, the metabolism of glucosamine was decreased and the metabolism of caffeine was increased. Our data provide new insights for marathon performance and nutritional status.
PubMed: 32190096
DOI: 10.1186/s12986-020-00436-0 -
The Journal of Physical Chemistry. C,... May 2022The adsorption of carboxylic acid molecules at the calcite (104) and the muscovite (001) surface was investigated using surface X-ray diffraction. All four investigated...
The adsorption of carboxylic acid molecules at the calcite (104) and the muscovite (001) surface was investigated using surface X-ray diffraction. All four investigated carboxylic acid molecules, hexanoic acid, octanoic acid, lauric acid, and stearic acid, were found to adsorb at the calcite surface. Whereas the shortest two carboxylic acid molecules, hexanoic acid and octanoic acid, showed limited ordering and a flexible, disordered chain, the two longest carboxylic acid molecules form fully ordered monolayers, i.e., these form highly structured self-assembled monolayers. The latter molecules are oriented almost fully upright, with a tilt of up to 10°. The oxygen atoms of the organic molecules are found at similar positions to those of water molecules at the calcite-water interface. This suggests that in both cases, the oxygen atoms compensate for the broken bonds at the calcite surface. Under the same experimental conditions, stearic acid does not adsorb to K and Ca-functionalized muscovite mica because the neutral molecules do not engage in the ionic bonds typical for the mica interface. These differences in adsorption behavior are characteristic for the differences of the oil-solid interactions in carbonate and sandstone reservoirs.
PubMed: 35655936
DOI: 10.1021/acs.jpcc.2c01157 -
Journal of Computational Chemistry Feb 2023The determination of gas phase thermochemical properties of per- and polyfluoroalkyl substances (PFAS) is central to understanding the long-range transport behavior of...
The determination of gas phase thermochemical properties of per- and polyfluoroalkyl substances (PFAS) is central to understanding the long-range transport behavior of PFAS in the atmosphere. Prior gas-phase studies have reported the properties of perfluorinated sulfonic acid (PFOS) and perfluorinated octanoic acid (PFOA). Here, this study reports the gas phase enthalpies of formation of short- and long-chain PFAS and their precursor molecules determined using density functional theory (DFT) and ab initio approaches. Two density functionals, two ab initio methods and an empirical method were used to compute enthalpies of formation with the total atomization approach and an isogyric reaction. The performance of the computational methods employed in this work were validated against the experimental enthalpies of linear alkanoic acids and perfluoroalkanes. The gas-phase determinations will be useful for future studies of PFAS in the atmosphere, and the methodological choices will be helpful in the study of other PFAS.
Topics: Alkanesulfonic Acids; Sulfonic Acids; Fluorocarbons; Thermodynamics; Environmental Pollutants
PubMed: 36334029
DOI: 10.1002/jcc.27023 -
G3 (Bethesda, Md.) Jan 2022Drosophila sechellia is a dietary specialist endemic to the Seychelles islands that has evolved to consume the fruit of Morinda citrifolia. When ripe, the fruit of M....
Drosophila sechellia is a dietary specialist endemic to the Seychelles islands that has evolved to consume the fruit of Morinda citrifolia. When ripe, the fruit of M. citrifolia contains octanoic acid and hexanoic acid, two medium-chain fatty acid volatiles that deter and are toxic to generalist insects. Drosophila sechellia has evolved resistance to these volatiles allowing it to feed almost exclusively on this host plant. The genetic basis of octanoic acid resistance has been the focus of multiple recent studies, but the mechanisms that govern hexanoic acid resistance in D. sechellia remain unknown. To understand how D. sechellia has evolved to specialize on M. citrifolia fruit and avoid the toxic effects of hexanoic acid, we exposed adult D. sechellia, D. melanogaster and D. simulans to hexanoic acid and performed RNA sequencing comparing their transcriptional responses to identify D. sechellia specific responses. Our analysis identified many more genes responding transcriptionally to hexanoic acid in the susceptible generalist species than in the specialist D. sechellia. Interrogation of the sets of differentially expressed genes showed that generalists regulated the expression of many genes involved in metabolism and detoxification whereas the specialist primarily downregulated genes involved in the innate immunity. Using these data, we have identified interesting candidate genes that may be critically important in aspects of adaptation to their food source that contains high concentrations of HA. Understanding how gene expression evolves during dietary specialization is crucial for our understanding of how ecological communities are built and how evolution shapes trophic interactions.
Topics: Animals; Caproates; Drosophila; Drosophila melanogaster; Genomics; Species Specificity
PubMed: 34718544
DOI: 10.1093/g3journal/jkab354