Review

Authors: Matthew Butawan, Rodney L Benjamin, Richard J Bloomer...

Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis; Biological Availability; Cartilage; Dietary Supplements; Dimethyl Sulfoxide; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Hypersensitivity; Inflammation; Myalgia; Neoplasms; Oxidative Stress; Risk Factors; Sulfones

PubMed: 28300758
DOI: 10.3390/nu9030290

Environmental Exposure to Emerging Alternatives of Per- and Polyfluoroalkyl Substances and Polycystic Ovarian Syndrome in Women Diagnosed with Infertility: A Mixture Analysis.

Authors: Wenqiang Zhan, Wei Qiu, Yan Ao...

BACKGROUND

Per- and polyfluoroalkyl substances (PFAS) have been previously linked to polycystic ovarian syndrome (PCOS), but only a few legacy PFAS were examined.

OBJECTIVES

This study aimed to explore this association with a variety of PFAS, including legacy, branched-chain isomers, and emerging alternatives, as well as a PFAS mixture.

METHODS

From 2014 to 2016, we conducted a multicenter, hospital-based case-control study on environmental endocrine disruptors and infertility in China. Three hundred sixty-six women with PCOS-related infertility and 577 control participants without PCOS were included in the current analysis. Twenty-three PFAS, including 3 emerging PFAS alternatives, 6 linear and branched PFAS isomers, 6 short-chain PFAS, and 8 legacy PFAS, were quantified in the plasma. Logistic regression and two multipollutant models [quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods] were used to assess the association of individual PFAS and PFAS mixture with PCOS, as well as the potential interactions among the congeners.

RESULTS

After adjusting for potential confounders, Each 1-standard deviation higher difference in ln-transformed 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) and hexafluoropropylene oxide dimer acid (HFPO-DA) level was significantly associated with a 29% (95% CI: 1.11, 1.52) and 39% (95% CI:1.16, 1.68) higher odds of PCOS, respectively. Meanwhile, branched isomers of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) (i.e., br-PFHxS, n-PFOS, , ), short-chain PFAS (i.e., PFPeS and PFHxA) and other legacy PFAS [i.e., total concentrations of PFOS (T-PFOS), and perfluorododecanoic acid (PFDoA)] were significantly associated with increased odds of PCOS. The PFAS mixture was positively related to PCOS in the BKMR model. A similar trend was observed in QGC model, a ln-unit increase in the PFAS mixture was associated with a 20% increased risk of PCOS [ (95% CI: 1.06, 1.37)]. After controlling for other PFAS homologs, 6:2 Cl-PFESA, HFPO-DA, , and PFDoA were the major contributors based on the QGC and BKMR models. The associations were more pronounced in overweight/obese women.

CONCLUSIONS

In this group of women, environmental exposure to a PFAS mixture was associated with an elevated odds of PCOS, with 6:2 Cl-PFESA, HFPO-DA, , and PFDoA being the major contributors, especially in overweight/obese women. https://doi.org/10.1289/EHP11814.

Topics: Humans; Female; Polycystic Ovary Syndrome; Case-Control Studies; Bayes Theorem; Overweight; Fluorocarbons; Environmental Exposure; Alkanesulfonic Acids; Infertility; Alkanesulfonates; Obesity; Environmental Pollutants

PubMed: 37134253
DOI: 10.1289/EHP11814

Authors: Yan Wang, Jingwen Zhang, Jiaxian Zhang...

BACKGROUND

No study has examined the association between per- and polyfluoroalkyl substances (PFAS) exposure and chronic obstructive pulmonary disease (COPD) risk. This study aims to explore this relationship.

METHODS

This study enrolled 4541 individuals who had available data on PFAS, COPD, and covariates from NHANES 2007-2018. Serum PFAS including perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) were analyzed, because of high detective rates. Considering the skew distribution of PFAS levels, the natural logarithm-transformed PFAS (Ln-PFAS) was used. Logistic regression analysis, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were performed to explore the single, nonlinear, and mixed effects. A mediating analysis was used to evaluate the mediated effects of albumin.

RESULTS

Individuals with COPD had higher levels of PFHxS, PFNA, PFOA, and PFOS compared to those without COPD. Ln-PFNA (OR : 1.92, 95 % CI:1.31 to 2.80, P: <0.001; OR : 1.07, 95 % CI: 0.81 to 1.40, P: 0.636) and ln-PFOA (OR : 2.17, 95 % CI:1.38 to 3.41, P: <0.001; OR : 1.49, 95 % CI: 1.08 to 2.05, P: 0.016) were associated with COPD risk especially in males. The interaction between PFNA exposure and sex on COPD risk was significant (P : <0.001). The RCS curve demonstrated the nonlinear relationship between the ln-PFOA (P :0.001), ln-PFNA (P :0.045), and COPD risk in males. WQS analysis showed mixed PFAS exposure was correlated with COPD risk in males (OR: 1.44, 95 % CI:1.18 to 1.75, P: <0.001). Albumin mediated the relationship between PFOA and COPD (mediated proportion: -17.94 %).

CONCLUSION

This study concludes PFOA and PFNA are linked to a higher COPD risk in males, and serum albumin plays a mediating role in the relationship between PFOA and COPD. Thess findings are beneficial for the prevention of COPD. Further studies are required to explore potential mechanisms.

Topics: Male; Female; Humans; Nutrition Surveys; Environmental Pollutants; Serum Albumin; Prevalence; Alkanesulfonic Acids; Fluorocarbons; Alkanesulfonates; Pulmonary Disease, Chronic Obstructive; Caprylates; Fatty Acids

PubMed: 38494022
DOI: 10.1016/j.scitotenv.2024.171742

Review

Authors: A M Cook, H Laue, F Junker...

Organosulfonates are widespread compounds, be they natural products of low or high molecular weight, or xenobiotics. Many commonly found compounds are subject to desulfonation, even if it is not certain whether all the corresponding enzymes are widely expressed in nature. Sulfonates require transport systems to cross the cell membrane, but few physiological data and no biochemical data on this topic are available, though the sequences of some of the appropriate genes are known. Desulfonative enzymes in aerobic bacteria are generally regulated by induction, if the sulfonate is serving as a carbon and energy source, or by a global network for sulfur scavenging (sulfate-starvation-induced (SSI) stimulon) if the sulfonate is serving as a source of sulfur. It is unclear whether an SSI regulation is found in anaerobes. The anaerobic bacteria examined can express the degradative enzymes constitutively, if the sulfonate is being utilized as a carbon source, but enzyme induction has also been observed. At least three general mechanisms of desulfonation are recognisable or postulated in the aerobic catabolism of sulfonates: (1) activate the carbon neighboring the C-SO3- bond and release of sulfite assisted by a thiamine pyrophosphate cofactor; (2) destabilize the C-SO3- bond by addition of an oxygen atom to the same carbon, usually directly by oxygenation, and loss of the good leaving group, sulfite; (3) an unidentified, formally reductive reaction. Under SSIS control, different variants of mechanism (2) can be seen. Catabolism of sulfonates by anaerobes was discovered recently, and the degradation of taurine involves mechanism (1). When anaerobes assimilate sulfonate sulfur, there is one common, unknown mechanism to desulfonate the inert aromatic compounds and another to desulfonate inert aliphatic compounds; taurine seems to be desulfonated by mechanism (1).

Topics: Alkanesulfonates; Bacteria, Anaerobic; Biodegradation, Environmental; Fermentation; Oxidation-Reduction

PubMed: 9990724
DOI: 10.1111/j.1574-6976.1998.tb00378.x

Relative inhibitory activities of newly developed diazabicyclooctanes, boronic acid derivatives, and penicillin-based sulfone β-lactamase inhibitors against broad-spectrum AmpC β-lactamases.

Authors: Christophe Le Terrier, Patrik Mlynarcik, Mustafa Sadek...

The relative inhibitory activities of diazabicyclooctanes (avibactam, relebactam, zidebactam, nacubactam, durlobactam), boronic acid derivatives (vaborbactam, taniborbactam, xeruborbactam), and penicillin-based sulfone derivative enmetazobactam were evaluated against several intrinsic and acquired class C β-lactamases. By contrast to vaborbactam and enmetazobactam, taniborbactam, xeruborbactam, and all diazabicyclooctanes demonstrated effective activities against most AmpC enzymes. Notably, durlobactam exhibited the most pronounced inhibitory effect. Interstingly, the chromosomal AmpC of was the least sensitive enzyme to the newly developed β-lactamase inhibitors.

Topics: Azabicyclo Compounds; beta-Lactamase Inhibitors; Boronic Acids; beta-Lactamases; Microbial Sensitivity Tests; Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Proteins; Penicillins; Sulfones; Bridged Bicyclo Compounds, Heterocyclic; Lactams; Piperidines; Cyclooctanes

PubMed: 39365068
DOI: 10.1128/aac.00775-24

Authors: Qinghua Tian, Yutong Yang, Qi An...

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

Authors: Xiuqi Ma, Jared A Fisher, Trang VoPham...

BACKGROUND AND AIM

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and in the serum of the U.S.

POPULATION

We sought to evaluate the association of PFAS independently and jointly with alcohol intake on liver function biomarkers in a sample of the U.S. general population.

METHODS

Using data from the National Health and Nutrition Examination Survey (2003-2016; N = 11,794), we examined the five most historically prevalent PFAS with >75% detection rates. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between PFAS (quartiles and log-transformed continuous, ng/mL) and high levels (>95th percentile) of liver injury biomarkers using logistic regression models adjusted for key confounders. We evaluated interactions between PFAS and alcohol consumption and sex via stratified analyses and conducted sub-analyses adjusting for daily alcohol intake among those with available drinking history (N = 10,316).

RESULT

Serum perfluorooctanoic acid (PFOA) was positively associated with high levels of alanine transferase (ALT) without monotonic trend (OR = 1.45, CI: 0.99-2.12; p-trend = 0.18), and with increased aspartate transaminase when modeled continuously (OR = 1.15, CI: 1.02-1.30; p-trend = 0.03). Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were both inversely associated with alkaline phosphatase while a trend was evident only for PFHxS (p = 0.02). A non-monotonic inverse association was observed with PFOA (p-trend = 0.10). The highest quartile of PFOS was associated with high total bilirubin (TB; OR = 1.57, CI: 1.01-2.43, p-trend = 0.02). No significant associations were found between any PFAS and γ-glutamyl transpeptidase. We found no associations for perfluorodecanoic acid and perfluorononanoic acid. We observed some suggestive interactions with alcohol intake, particularly among heavy drinkers.

CONCLUSION

Consistent with other studies, serum levels of PFOA, PFHxS and PFNA were positively associated with high levels of ALT, and we also observed weak positive associations between some PFAS and TB. Associations observed among heavy drinkers warrant additional evaluation.

Topics: Humans; Adult; Environmental Pollutants; Nutrition Surveys; Alkanesulfonic Acids; Fluorocarbons; Alkanesulfonates; Liver; Biomarkers; Alcohol Drinking

PubMed: 37451576
DOI: 10.1016/j.envres.2023.116651

Authors: Benjamin K Raliski, Dong Min Mun, Evan W Miller...

Fluorescent indicators that respond to changes in biological membrane potentials provide a powerful complement to existing methods for monitoring neuronal activity. Indicators that absorb and emit in the near infrared window are especially attractive, since lower energy wavelengths excite fewer biological molecules and can penetrate more deeply into biological tissues. In this work, we incorporate sulfone rhodamine chromophores into a voltage-sensitive scaffold in order to generate voltage sensitive fluorophores which absorb and emit above 700 nm. These Sulfone Rhodamine Voltage Reporters (SuRhoVRs) partition into cell membranes and display good sensitivity to membrane potential changes. The most sensitive SuRhoVR derivative also displays excellent photostability and can track membrane potential changes in dissociated rat hippocampal neurons.

Topics: Rats; Animals; Rhodamines; Fluorescent Dyes; Diagnostic Imaging; Sulfones

PubMed: 36356288
DOI: 10.1002/asia.202200906

Meta-Analysis

Authors: Fang Xiao, Ziwen An, Junli Lv...

BACKGROUND

Existing evidence indicates that exposure to per- and polyfluoroalkyl substances (PFASs) may increase the risk of hypertension, but the findings are inconsistent. Therefore, we aimed to explore the relationship between PFASs and hypertension through this systematic review and meta-analysis.

METHODS

We searched PubMed, Embase, and the Web of Science databases for articles published in English that examined the relationship between PFASs and hypertension before 13 August 2022. The random effects model was used to aggregate the evaluation using Stata 15.0 for Windows. We also conducted subgroup analyses by region and hypertension definition. In addition, a sensitivity analysis was carried out to determine the robustness of the findings.

RESULTS

The meta-analysis comprised 15 studies in total with 69,949 individuals. The risk of hypertension was substantially and positively correlated with exposure to perfluorooctane sulfonate (PFOS) (OR = 1.31, 95% CI: 1.14, 1.51), perfluorooctanoic acid (PFOA) (OR = 1.16, 95% CI: 1.07, 1.26), and perfluorohexane sulfonate (PFHxS) (OR = 1.04, 95% CI: 1.00, 1.09). However, perfluorononanoic acid (PFNA) exposure and hypertension were not significantly associated (OR = 1.08, 95% CI: 0.99, 1.17).

CONCLUSION

We evaluated the link between PFASs exposure and hypertension and discovered that higher levels of PFOS, PFOA, and PFHxS were correlated with an increased risk of hypertension. However, further high-quality population-based and pathophysiological investigations are required to shed light on the possible mechanism and demonstrate causation because of the considerable variability.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/prospero/ PROSPERO, registration number: CRD 42022358142.

Topics: Humans; Alkanesulfonates; Fluorocarbons; Hypertension

PubMed: 37655293
DOI: 10.3389/fpubh.2023.1173101

Authors: Penghui Nie, Yuzhi Lan, Tao You...

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as pollutants, can cause palpable environmental and health impacts around the world, as endocrine disruptors, can disrupt endocrine homeostasis and increase the risk of diseases. Chlorinated polyfluoroalkyl ether sulfonate (F-53B), as a substitute for PFAS, was determined to have potential toxicity. Puberty is the stage when sexual organs develop and hormones change dramatically, and abnormal uterine development can increase the risk of uterine lesions and lead to infertility. This study was designed to explore the impact of F-53B on uterine development during puberty. Four-week-old female SD rats were exposed to 0.125 and 6.25 mg/L F-53B during puberty. The results showed that F-53B interfered with growth and sex hormone levels and bound to oestrogen-related receptors, which affected their function, contributed to the accumulation of reactive oxygen species, promoted cell apoptosis and inhibited cell proliferation, ultimately causing uterine dysplasia.

Topics: Animals; Female; Rats; Apoptosis; Cell Proliferation; Endocrine Disruptors; Environmental Pollutants; Fluorocarbons; Rats, Sprague-Dawley; Reactive Oxygen Species; Receptors, Estrogen; Sexual Maturation; Uterus; Alkanesulfonates

PubMed: 38677070
DOI: 10.1016/j.ecoenv.2024.116399