Elsevier

Environmental Pollution

Volume 315, 15 December 2022, 120403
Environmental Pollution

Effects of perfluorobutane sulfonate and perfluorooctane sulfonate on lipid homeostasis in mouse liver

https://doi.org/10.1016/j.envpol.2022.120403Get rights and content

Highlights

  • Adverse effects of low-dose PFBS and PFOS on mouse livers were compared.

  • No liver damage was observed at the phenotypic level after 10 μg/L PFBS exposure.

  • Exposure of 500 μg/L PFBS and PFOS induced liver damage.

  • Lipidomic profiles induced by PFBS were different from those of PFOS.

  • PFBS exposure altered abundance of phosphatidylcholines, sphingomyelins, and phosphatidylinositols.

Abstract

Perfluorobutane sulfonate (PFBS), an alternative to perfluorooctane sulfonate (PFOS), has been increasingly used in recent years. However, emerging evidence has raised concerns about the potential health risks of PFBS. Here, the toxicityof low-dose PFBS on livers was explored and compared with that of PFOS. Adult C57BL/6 mice were exposed to 10 μg/L, 500 μg/L PFBS, or 500 μg/L PFOS for 28 days through drinking water. At the phenotypic level, no liver damage was observed in the 10 μg/L PFBS group. The cell apoptosis and decrease of CAT activities were observed in the 500 μg/L PFBS group, while accumulation of lipid droplets, increase of CAT activities and TAG levels were found in the 500 μg/L PFOS group. Lipidomics analysis revealed that 138, 238, and 310 lipids were significantly changed in the 10 μg/L, 500 μg/L PFBS and 500 μg/L PFOS groups, respectively. The two PFBS-treated groups induced similar global lipid changes in a dose-dependent manner, which were distinct from PFOS. Overall, PFBS exposure induced an increase in phosphatidylcholines and sphingomyelins, but a decrease in phosphatidylinositol. PFOS exposure caused an increase in triacylglycerols. This study provides more evidence on the health hazards caused by exposure to low-dose PFBS.

Introduction

Perfluorobutane sulfonate (PFBS) is a short-chain per- and polyfluoroalkyl substances (PFASs). Since perfluorooctane sulfonate (PFOS) was phased out under the facilitation of the Stockholm Convention on Persistent Organic Pollutants (POPs) in 2009, PFBS was widely produced and used as an alternative for PFOS (Tang et al., 2020). However, the large-scale manufacture and application have turned PFBS into an emerging environmental contaminant of international interest (Annunziato et al., 2022). Generally, PFBS is detected in surface water (Sun et al., 2018), groundwater (Bertanza et al., 2020), and piped drinking water (Schwanz et al., 2016) at levels ranging from tens to hundreds of ng/L. However, PFBS can reach μg/L in waters influenced by discharge of industrial and municipal wastewater. For example, PFBS levels as high as 8.0 μg/L were recently detected in Tangxun Lake of Hubei Province, China (Chen et al., 2020), and 21.2 μg/L PFBS were also determined in groundwater under a fluorochemical industrial park (Bao et al., 2019). Apparently, humans are threatened by PFBS exposure by the intake of contaminated water. In fact, PFBS has already been detected in human populations with an increasing trend (Glynn et al., 2012). Thus, the impact of PFBS on human health is becoming an urgent issue to be explored.

Unlike extensively researched PFOS, a small number of studies have reported the adverse effects of PFBS on mammals. It was reported that an increase in liver weight and hepatocellular hypertrophy were found in rats exposed to 300 and 1000 mg/kg/day PFBS for 10 weeks (Lieder et al., 2009). The exposure of 300 mg/kg body weight PFBS for 24 h induced the elevated expression of several genes targeted for PPARα, PPARy, and PXR in mouse livers (Lau et al., 2020). Other evidence showed that the exposure of adult female mice to PFBS (200 mg/kg/day) for 14 days decreased the total triiodothyronine and thyroxine levels in serum (Cao et al., 2020). In vitro studies showed that 10–200 μM PFBS treatment for 6 days increased the adipogenesis of 3T3-L1 adipocytes (Qi et al., 2018). Exposure to 200 μM PFBS increased the lipogenesis gene expression in HepG2 human hepatoma (Qi et al., 2020). Although these studies revealed that high-dose PFBS exposure could cause hepatoxicity, endocrine disruption, changes in gene expressions, and lipid homeostasis, adverse effects of PFBS at environmentally relevant concentrations on mammals are still unclear.

Several currently reported toxicities of PFBS are related to hepatic lipid homeostasis, which has also been shown to play a vital role in the toxicity of PFOS (Wang et al., 2020a; Zeng et al., 2019b). Lipids are an important class of small molecules present in organisms, which are involved in various biological processes, including membrane architecture, energy homeostasis, inflammation, cellular signaling, and transduction of cellular events (Van Meulebroek et al., 2017). Dysregulation of lipid homeostasis has been reported to be associated with various diseases including cancer, diabetes, atherosclerosis, multiple sclerosis, neurodegenerative diseases and so on (Teo et al., 2015). Thus, the deep analysis of lipid alterations may yield valuable insights into human health risks induced by PFBS exposure. However, the global lipid changes induced by PFBS exposure in mammals were still less understood. The emerging lipidomics aims to obtain a more comprehensive characterization of lipid behavior in a biotic sample, which provides a powerful tool for solving the above question (Van Meulebroek et al., 2017).

Here, we hypothesize that adverse effects on mouse livers after low-dose PFBS exposure might not be apparent at the phenotypic level, and more sensitive endpoints such as the global lipid profiles could be an informative tool to investigate the toxicity. To better understand this toxicity induced by PFBS exposure, PFBS and PFOS were simultaneously exposed to mice for comparative study. The histological and biochemical analyses were used to characterize toxicity in liver at phenotypic levels. Then, the MS-based untargeted lipidomics was used to comprehensively analyze lipid homeostasis. This study provides reference data for health risk assessment caused by PFBS exposure at environmentally relevant concentrations.

Section snippets

Animals treatment

Specific pathogen-free adult C57BL/6 mice (body weight of 25–26 g) were provided by Shanghai SLAC Laboratory Animal Company (Shanghai, China). Only male mice were selected to avoid metabolic disorders caused by female physiological changes. Mice were housed in stainless-steel cages under standard conditions (temperature, 24 ± 0.5 °C; humidity, 50 ± 5%; light/dark cycle, 12 h/12 h). After acclimation for two weeks, the mice were randomly assigned into four groups. One group was the control group

Accumulation of PFBS and PFOS in liver

Actual average PFBS concentrations in drinking water were maintained at 8.24 ± 0.06 and 418.81 ± 24.83 μg/L in the 10 μg/L and 500 μg/L PFBS exposure groups, respectively. And the PFOS concentration in drinking water was 446.64 ± 14.73 μg/L in the 500 μg/L PFOS exposure group. Deviations between nominal and actual concentrations were <20%. Data on the daily water intake of each group are shown in Table S1. After exposure to 10 μg/L and 500 μg/L PFBS for 28 days, PFBS levels in the livers were

Conclusions

This study systematically compared the bioaccumulation, toxicity, and mechanisms of PFBS and PFOS at low-dose exposure. Our results suggested that PFOS is easier to accumulate in mouse livers than its substitute PFBS, which could be the most important contributor to the difference in toxicity of strength at the same exposure concentration. Combined using the phenotypic analysis and lipidomics, this study revealed that PFBS exposure caused toxicity on mouse liver by inhibiting antioxidant enzyme

Author contributions statement

Ling Chen: Conceptualization, Methodology, Software, Investigation, Data curation, Writing – original draft. Yafeng Liu: Methodology, Investigation, Data curation. Hongxin Mu: Methodology, Investigation, Data curation. Huan Li: Methodology, Writing – review & editing. Su Liu: Investigation, Writing – review & editing. Mengyuan Zhu: Writing – review & editing. Yuanqing Bu: Writing - review & editing. Bing Wu: Conceptualization, Writing – review & editing, Supervision, Funding acquisition.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This study was supported by the Natural Science Foundation of Jiangsu Province (BK20200011), and the Fundamental Research Funds for the Central Universities (021114380170), the Research Program of State Key Laboratory of Pollution Control and Resource Reuse (PCRR-ZZ-202104), and the Excellent Research Program of Nanjing University (ZYJH005).

References (56)

  • E. Gorrochategui et al.

    Perfluorinated chemicals: differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    Toxicol. Appl. Pharmacol.

    (2014)
  • C. Hu et al.

    Metabolomic profiles in zebrafish larvae following probiotic and perfluorobutanesulfonate coexposure

    Environ. Res.

    (2022)
  • C. Hu et al.

    Fecal transplantation from young zebrafish donors efficiently ameliorates the lipid metabolism disorder of aged recipients exposed to perfluorobutanesulfonate

    Sci. Total Environ.

    (2022)
  • R. Kannan et al.

    Ceramide-induced apoptosis: role of catalase and hepatocyte growth factor

    Free Radic. Biol. Med.

    (2004)
  • C. Lau et al.

    Pharmacokinetic profile of perfluorobutane sulfonate and activation of hepatic nuclear receptor target genes in mice

    Toxicology

    (2020)
  • P.H. Lieder et al.

    A two-generation oral gavage reproduction study with potassium perfluorobutanesulfonate (K+PFBS) in Sprague Dawley rats

    Toxicology

    (2009)
  • M. Liu et al.

    Antagonistic interaction between perfluorobutanesulfonate and probiotic on lipid and glucose metabolisms in the liver of zebrafish

    Aquat. Toxicol.

    (2021)
  • H. Mu et al.

    Distribution, source and ecological risk of per- and polyfluoroalkyl substances in Chinese municipal wastewater treatment plants

    Environ. Int.

    (2022)
  • W. Qi et al.

    Perfluorobutanesulfonic acid (PFBS) potentiates adipogenesis of 3T3-L1 adipocytes

    Food Chem. Toxicol.

    (2018)
  • M. Record et al.

    Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies

    Biochim. Biophys. Acta Mol. Cell Biol. Lipids

    (2014)
  • S. Rodriguez-Cuenca et al.

    Sphingolipids and glycerophospholipids - the "ying and yang" of lipotoxicity in metabolic diseases

    Prog. Lipid Res.

    (2017)
  • K. Roth et al.

    Exposure to a mixture of legacy, alternative, and replacement per- and polyfluoroalkyl substances (PFAS) results in sex-dependent modulation of cholesterol metabolism and liver injury

    Environ. Int.

    (2021)
  • T.G. Schwanz et al.

    Perfluoroalkyl substances assessment in drinking waters from Brazil, France and Spain

    Sci. Total Environ.

    (2016)
  • R. Sun et al.

    Perfluorinated compounds in surface waters of Shanghai, China: source analysis and risk assessment. Ecotox

    Environ. Safe.

    (2018)
  • C.C. Teo et al.

    Advances in sample preparation and analytical techniques for lipidomics study of clinical samples

    Trac-Trends Anal. Chem.

    (2015)
  • H.T. Wan et al.

    PFOS-induced hepatic steatosis, the mechanistic actions on beta-oxidation and lipid transport

    Biochim. Biophys. Acta-Gen. Subj.

    (2012)
  • R. Wang et al.

    Integration of lipidomics and metabolomics for in-depth understanding of cellular mechanism and disease progression

    J. Genet. Genomics

    (2020)
  • X. Wang et al.

    Perfluorooctane sulfonate triggers tight junction "opening" in brain endothelial cells via phosphatidylinositol 3-kinase

    Biochem. Biophys. Res. Commun.

    (2011)
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