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Molecules (Basel, Switzerland) Sep 2021Piglet coccidiosis due to is a major cause of diarrhea and poor growth worldwide. It can effectively be controlled by application of toltrazuril (TZ), and oral...
Piglet coccidiosis due to is a major cause of diarrhea and poor growth worldwide. It can effectively be controlled by application of toltrazuril (TZ), and oral formulations have been licensed for many years. Recently, the first parenteral formulation containing TZ in combination with iron (gleptoferron) was registered in the EU for the prevention of coccidiosis and iron deficiency anemia, conditions in suckling piglets requiring routine preventive measures. This study evaluated the absorption and distribution of TZ and its main metabolite, toltrazuril sulfone (TZ-SO), in blood and intestinal tissues after single oral (20 mg/kg) or single intramuscular (45 mg/piglet) application of TZ. Fifty-six piglets were randomly allocated to the two treatment groups. Animals were sacrificed 1-, 5-, 13-, and 24-days post-treatment and TZ and TZ-SO levels were determined in blood, jejunal tissue, ileal tissue, and mixed jejunal and ileal content (IC) by high performance liquid chromatography (HPLC). Intramuscular application resulted in significantly higher and more sustained concentrations of both compounds in plasma, intestinal tissue, and IC. Higher concentrations after oral dosing were only observed one day after application of TZ in jejunum and IC. Toltrazuril was quickly metabolized to TZ-SO with maximum concentrations on day 13 for both applications. Remarkably, TZ and TZ-SO accumulated in the jejunum, the primary predilection site of , independently of the administration route, which is key to their antiparasitic effect.
Topics: Administration, Oral; Animals; Body Weight; Coccidiosis; Coccidiostats; Ileum; Injections, Intramuscular; Intestinal Mucosa; Jejunum; Sulfones; Swine; Swine Diseases; Triazines
PubMed: 34577103
DOI: 10.3390/molecules26185633 -
Environmental Health Perspectives Nov 2023Perfluorohexane sulfonate (PFHxS) is a frequently detected per- and polyfluoroalkyl substance in most populations, including in individuals who are pregnant, a period...
BACKGROUND
Perfluorohexane sulfonate (PFHxS) is a frequently detected per- and polyfluoroalkyl substance in most populations, including in individuals who are pregnant, a period critical for early life development. Despite epidemiological evidence of exposure, developmental toxicity, particularly at realistic human exposures, remains understudied.
OBJECTIVES
We evaluated the effect of gestational exposure to human-relevant body burden of PFHxS on fetal and placental development and explored mechanisms of action combining alternative splicing (AS) and gene expression (GE) analyses.
METHODS
Pregnant ICR mice were exposed to 0, 0.03, and from gestational day 7 to day 17 via oral gavage. Upon euthanasia, PFHxS distribution was measured using liquid chromatography-tandem mass spectrometry. Maternal and fetal phenotypes were recorded, and histopathology was examined for placenta impairment. Multiomics was adopted by combining AS and GE analyses to unveil disruptions in mRNA quality and quantity. The key metabolite transporters were validated by quantitative real-time PCR (qRT-PCR) for quantification and three-dimensional (3D) structural simulation by AlphaFold2. Targeted metabolomics based on liquid chromatography-tandem mass spectrometry was used to detect amino acid and amides levels in the placenta.
RESULTS
Pups developmentally exposed to PFHxS exhibited signs of intrauterine growth restriction (IUGR), characterized by smaller fetal weight and body length () compared to control mice. PFHxS concentration in maternal plasma was . PFHxS trans-placenta distribution suggested dose-dependent transfer through placental barrier. Histopathology of placenta of exposed dams showed placental dysplasia, manifested with an attenuated labyrinthine layer area and deescalated blood sinus counts and placental vascular development index marker CD34. Combined GE and AS analyses pinpointed differences in genes associated with key biological processes of placental development, proliferation, metabolism, and transport in placenta of exposed dams compared to that of control dams. Further detection of placental key transporter gene expression, protein structure simulation, and amino acid and amide metabolites levels suggested that PFHxS exposure during pregnancy led to impairment of placental amino acid transportation.
DISCUSSION
The findings from this study suggest that exposure to human-relevant very-low-dose PFHxS during pregnancy in mice caused IUGR, likely via downregulating of placental amino acid transporters, thereby impairing placental amino acid transportation, resulting in impairment of placental development. Our findings confirm epidemiological findings and call for future attention on the health risk of this persistent yet ubiquitous chemical in the early developmental stage and provide a new approach for understanding gene expression from both quantitative and qualitative omics approaches in toxicological studies. https://doi.org/10.1289/EHP13217.
Topics: Humans; Pregnancy; Mice; Animals; Female; Placentation; Placenta; Alternative Splicing; Mice, Inbred ICR; Fluorocarbons; Alkanesulfonates; Fetal Growth Retardation; Amino Acids; Gene Expression Profiling
PubMed: 37995155
DOI: 10.1289/EHP13217 -
Molecules (Basel, Switzerland) Aug 2023Numerous plants of medicinal value grow on Hainan Island (China). Given the lack of knowledge on the phytochemical and pharmacological properties of Chun and Y. F. Wu...
Numerous plants of medicinal value grow on Hainan Island (China). Given the lack of knowledge on the phytochemical and pharmacological properties of Chun and Y. F. Wu (), the application of natural antioxidants and antimicrobials in the food industry has attracted increasing interest. This study aimed to compare the chemical composition, free-radical-scavenging capacity, and antibiosis of aqueous extracts of the fresh and dried leaves of The aqueous extract of the leaves of was obtained using steam distillation, and its chemical components were separated and identified via gas chromatography-mass spectrometry (GC-MS). The free-radical-scavenging capacity and antibiosis were determined. Further, 28 and 20 compounds were isolated from the fresh leaf aqueous extract of (MSFLAE) and dried leaf aqueous extract of (MSDLAE), respectively. The free-radical-scavenging capacity of MSFLAE and MSDLAE was determined by the 2,2-diphenyl-1 picrylhydrazyl (DPPH) method, which was 43.43% and 38.74%, respectively. The scavenging capacity of MSFLAE and MSDLAE determined by the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate (ABTS)) method was 46.90% and 25.99%, respectively. The iron ion reduction capacity of MSFLAE and MSDLAE was determined by the ferric-reducing antioxidant power (FRAP) method as 94.7 and 62.9 μmol Fe⁺/L, respectively. This indicated that the two leaf aqueous extracts had a certain free-radical-scavenging capacity, and the capacity of MSFLAE was higher than that of MSDLAE. The antibiosis of the two leaf aqueous extracts on the three foodborne pathogenic bacteria was low, but the antimicrobial effects on Gram-positive bacteria were better than those on Gram-negative bacteria. The antibiosis of MSFLAE on and was greater than that of MSDLAE. Finally, MSFLAE and MSDLAE both had certain free-radical-scavenging capacities and antibiosis, confirming that the use of this plant in the research and development of natural antioxidants and antibacterial agents was reasonable. Plant aqueous extracts are an essential source of related phytochemistry and have immense pharmacological potential.
Topics: Antibiosis; Steam; Alkanesulfonates; Anti-Bacterial Agents; Antioxidants; Escherichia coli; Magnoliaceae
PubMed: 37630187
DOI: 10.3390/molecules28165935 -
Proceedings of the National Academy of... Mar 2022SignificanceBisphenol A (BPA), found in many plastic products, has weak estrogenic effects that can be harmful to human health. Thus, structurally related...
SignificanceBisphenol A (BPA), found in many plastic products, has weak estrogenic effects that can be harmful to human health. Thus, structurally related replacements-bisphenol S (BPS) and bisphenol F (BPF)-are coming into wider use with very few data about their biological activities. Here, we compared the effects of BPA, BPS, and BPF on human mammary organoids established from normal breast tissue. BPS disrupted organoid architecture and induced supernumerary branching. At a proteomic level, the bisphenols altered the abundance of common targets and those that were unique to each compound. The latter included proteins linked to tumor-promoting processes. These data highlighted the importance of testing the human health effects of replacements that are structurally related to chemicals of concern.
Topics: Benzhydryl Compounds; Carcinogenesis; Estrogens; Humans; Mammary Glands, Human; Organoids; Phenols; Proteome; Proteomics; Sulfones
PubMed: 35263230
DOI: 10.1073/pnas.2115308119 -
Environment International Jul 2023Perfluorohexyl sulfonate (PFHxS) is the third most abundant per- and polyfluoroalkyl substances and its developmental toxicity remains very poorly understood. Here,...
Perfluorohexyl sulfonate (PFHxS) is the third most abundant per- and polyfluoroalkyl substances and its developmental toxicity remains very poorly understood. Here, pregnant mice exposed to PFHxS at human relevant dose showed increased fetal death incidence in the high-dose PFHxS-H group (P < 0.01). Body distribution analyses suggested that PFHxS crossed the placental barrier reaching the fetus in a dose-dependent manner. Histopathological data demonstrated impairment in the placenta with reduced blood sinus volume, placental labyrinth area as well as thickness of labyrinthine layer. Further lipidomic and transcriptomic data together showed that PFHxS exposure caused significant disruption in placental lipid homeostasis, including total lipid accumulation in the placenta, and dysregulation in phospholipid and glycerol lipid metabolism. Gene expression analyses uncovered elevation in key placental fatty acid transporters including fabp2, whereas protein expression showed transporter specific disruptions following exposure. Together, gestational exposure to human relevant level of PFHxS may increase the incidence of fetal deaths and caused placental dysplasia via disruption in lipid metabolism homeostasis. These findings raise the concern regarding the highly prevalent and persistent chemical towards early sensitive developing stages and provide basis for further understanding of its effects on lipid metabolism and underlying mechanisms.
Topics: Humans; Pregnancy; Female; Mice; Animals; Placenta; Alkanesulfonates; Fluorocarbons; Fatty Acids; Homeostasis
PubMed: 37315490
DOI: 10.1016/j.envint.2023.108014 -
American Journal of Industrial Medicine May 2023Firefighters have occupational and environmental exposures to per- and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations...
BACKGROUND
Firefighters have occupational and environmental exposures to per- and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants.
METHODS
Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A-D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES.
RESULTS
In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A-C, sum of branched perfluoromethylheptane sulfonate isomers (Sm-PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n-PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n-PFOA) was elevated in Departments B-D, and perfluorononanoate (PFNA) was elevated in Departments B-D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B-D. In female firefighters compared with NHANES, PFHxS and Sm-PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department.
CONCLUSIONS
Serum PFHxS, Sm-PFOS, n-PFOS, n-PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.
Topics: Humans; Male; Female; United States; Nutrition Surveys; Fluorocarbons; Environmental Exposure; Alkanesulfonates; Environmental Pollutants
PubMed: 35864570
DOI: 10.1002/ajim.23413 -
Environmental Pollution (Barking, Essex... Sep 2022Research on per- and polyfluoroalkyl substances (PFAS) in freshwater ecosystems has focused primarily on legacy compounds and little is still known on the presence of...
Research on per- and polyfluoroalkyl substances (PFAS) in freshwater ecosystems has focused primarily on legacy compounds and little is still known on the presence of emerging PFAS. Here, we investigated the occurrence of 60 anionic, zwitterionic, and cationic PFAS in a food web of the St. Lawrence River (Quebec, Canada) near a major metropolitan area. Water, sediments, aquatic vegetation, invertebrates, and 14 fish species were targeted for analysis. Levels of perfluorobutanoic acid (PFBA) in river water exceeded those of perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS), and a zwitterionic betaine was observed for the first time in the St. Lawrence River. The highest mean PFAS concentrations were observed for the benthopelagic top predator Smallmouth bass (Micropterus dolomieu, ΣPFAS ∼ 92 ± 34 ng/g wet weight whole-body) and the lowest for aquatic plants (0.52-2.3 ng/g). Up to 33 PFAS were detected in biotic samples, with frequent occurrences of emerging PFAS such as perfluorobutane sulfonamide (FBSA) and perfluoroethyl cyclohexane sulfonate (PFECHS), while targeted ether-PFAS all remained undetected. PFOS and long-chain perfluorocarboxylates (C10-C13 PFCAs) dominated the contamination profiles in biota except for insects where PFBA was predominant. Gammarids, molluscs, and insects also had frequent detections of PFOA and fluorotelomer sulfonates, an important distinction with fish and presumably due to different metabolism. Based on bioaccumulation factors >5000 and trophic magnification factors >1, long-chain (C10-C13) PFCAs, PFOS, perfluorodecane sulfonate, and perfluorooctane sulfonamide qualified as very bioaccumulative and biomagnifying. Newly monitored PFAS such as FBSA and PFECHS were biomagnified but moderately bioaccumulative, while PFOA was biodiluted.
Topics: Alkanesulfonates; Alkanesulfonic Acids; Animals; Bioaccumulation; Ecosystem; Environmental Monitoring; Fishes; Fluorocarbons; Food Chain; Rivers; Sulfonamides; Water; Water Pollutants, Chemical
PubMed: 35817301
DOI: 10.1016/j.envpol.2022.119739 -
Cell Biology and Toxicology Apr 2021Methylsulfonylmethane (MSM) is a commonly used diet supplement believed to decrease the inflammation in joints and fastens recovery in osteoarthritis, gastric mucosal...
BACKGROUND
Methylsulfonylmethane (MSM) is a commonly used diet supplement believed to decrease the inflammation in joints and fastens recovery in osteoarthritis, gastric mucosal injury, or obesity-related disorders. It was also suggested that MSM might play a beneficial role in cancer treatment.
PURPOSE
So far, the MSM might have a potentially beneficial effect in endometrial cancer (EC) treatment.
STUDY DESIGN
This study evaluated the effect and usefulness of MSM in combinatory therapy with known drug doxorubicin (DOX).
METHODS
The effect of combinational treatment of MSM and DOX on the induction of apoptosis was evaluated in EC cell lines (ISHIKAWA, MFE-296, MFE-280).
RESULTS
We observed that MSM itself induces apoptosis in EC cell lines, and pre-treatment with MSM for 24 h increases the sensitivity of EC cells to DOX-induced apoptosis and DNA damage and that effect might be regulated by p42/44 (Erk1/2) MAPK and Akt (protein kinase B).
CONCLUSION
These results for the first time show that MSM might act as a sensitizer of EC cells to known drugs, for which EC cells quickly acquire resistance. Graphical abstract.
Topics: Apoptosis; Cell Line, Tumor; Cell Survival; Dimethyl Sulfoxide; Doxorubicin; Endometrial Neoplasms; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Mitogen-Activated Protein Kinase 3; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-akt; Sulfones; Superoxide Dismutase
PubMed: 32562081
DOI: 10.1007/s10565-020-09542-4 -
Frontiers in Public Health 2024To investigate the relationships between perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure and glucose metabolism indices.
OBJECTIVE
To investigate the relationships between perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure and glucose metabolism indices.
METHODS
Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 waves were used. A total of 611 participants with information on serum PFASs (perfluorononanoic acid (PFNA); perfluorooctanoic acid (PFOA); perfluoroundecanoic acid (PFUA); perfluorohexane sulfonic acid (PFHxS); perfluorooctane sulfonates acid (PFOS); perfluorodecanoic acid (PFDeA)), glucose metabolism indices (fasting plasma glucose (FPG), homeostasis model assessment for insulin resistance (HOMA-IR) and insulin) as well as selected covariates were included. We used cluster analysis to categorize the participants into three exposure subgroups and compared glucose metabolism index levels between the subgroups. Least absolute shrinkage and selection operator (LASSO), multiple linear regression analysis and Bayesian kernel machine regression (BKMR) were used to assess the effects of single and mixed PFASs exposures and glucose metabolism.
RESULTS
The cluster analysis results revealed overlapping exposure types among people with higher PFASs exposure. As the level of PFAS exposure increased, FPG level showed an upward linear trend ( < 0.001), whereas insulin levels demonstrated a downward linear trend ( = 0.012). LASSO and multiple linear regression analysis showed that PFNA and FPG had a positive relationship (>50 years-old group: = 0.059, < 0.001). PFOA, PFUA, and PFHxS (≤50 years-old group: insulin = -0.194, < 0.001, HOMA-IR = -0.132, = 0.020) showed negative correlation with HOMA-IR/insulin. PFNA (>50 years-old group: insulin = 0.191, = 0.018, HOMA-IR = 0.220, = 0.013) showed positive correlation with HOMA-IR/insulin, which was essentially the same as results that obtained for the univariate exposure-response map in the BKMR model. Association of exposure to PFASs on glucose metabolism indices showed positive interactions between PFOS and PFHxS and negative interactions between PFOA and PFNA/PFOS/PFHxS.
CONCLUSION
Our study provides evidence that positive and negative correlations between PFASs and FPG and HOMA-IR/insulin levels are observed, respectively. Combined effects and interactions between PFASs. Given the higher risk of glucose metabolism associated with elevated levels of PFAS, future studies are needed to explore the potential underlying mechanisms.
Topics: Humans; Middle Aged; Environmental Pollutants; Nutrition Surveys; Bayes Theorem; Fluorocarbons; Alkanesulfonates; Glucose; Insulins; Caprylates; Fatty Acids; Sulfonic Acids
PubMed: 38633237
DOI: 10.3389/fpubh.2024.1370971 -
Toxicology and Applied Pharmacology Nov 2020Bisphenol S (BPS) is a component of polyether sulfone used in a variety of industrial applications and consumer products. We investigated the plasma toxicokinetic (TK)...
Bisphenol S (BPS) is a component of polyether sulfone used in a variety of industrial applications and consumer products. We investigated the plasma toxicokinetic (TK) behavior of free (unconjugated parent) and total (parent and conjugated) BPS in rats and mice following a single gavage administration (34, 110, or 340 mg/kg). In male rats, BPS was rapidly absorbed with free BPS maximum concentration (C) reached at ≤2.27 h. Elimination of free BPS in male rats was dose-dependent with estimated half-lives of 5.77-11.9 h. C and area under the concentration versus time curve (AUC) increased with dose although the increase in AUC was more than dose proportional. In male rats, total BPS C was reached ≤2.77 h with both C (≥ 10-fold) and AUC (≥ 15-fold) higher than free BPS demonstrating rapid and extensive conjugation of BPS. In male mice, the increase in C and AUC of free BPS was dose-proportional; C was higher and AUC was lower than in male rats. BPS was cleared more rapidly in male mice (half-life 2.86-4.21 h) compared to male rats (half-life 5.77-11.9 h). Similar to rats, total BPS C (≥ 6-fold) and AUC (≥ 12-fold) were higher than corresponding free BPS. Oral bioavailability of free BPS was low to moderate (rats, ≤ 21%; mice, ≤ 19%). There were some species differences in TK parameters of free and total BPS and limited sex difference in rats and mice. In addition, there were dose-related effects of plasma TK parameters in rats.
Topics: Administration, Intravenous; Administration, Oral; Animals; Biological Availability; Female; Male; Mice; Phenols; Rats; Sex Characteristics; Sulfones
PubMed: 32853628
DOI: 10.1016/j.taap.2020.115207