Both sub-acute, Moderate-Dose and Short-Term, Low-Dose Dietary Exposure of Mice to Perfluorooctane Sulfonate Exacerbates Concanavalin A-Induced Hepatitis
Abstract
Exposure of rodents to perfluorooctane sulfonate (PFOS) induces pronounced hepatomegaly associated with significant alterations in hepatic histophysiology and immune status. The present investigation was designed to evaluate the effects of this perfluorochemical on immune-mediated liver damage. Accordingly, the influence of both sub-acute (10 days), moderate-dose (0.004%, w/w=6±1.3 mg/kg body weight/day) or short-term (28 days), low-dose (0.0001%, w/w=144±4 μg/kg body weight/day) dietary pretreatment with PFOS on the development of concanavalin A (Con A)-induced liver damage in mice was examined. With either regimen of exposure, PFOS exacerbated the acute liver damage caused by Con A, i.e., elevated serum levels of transaminases and led to more pronounced damage of hepatic tissue. This exacerbation was associated with either reduced (moderate dose) or unaltered (low dose) hepatic levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). Moreover, hepatic DNA fragmentation was enhanced, particularly following short-term exposure to a low-dose. Our findings suggest that exposure to PFOS may sensitize hepatic parenchymal cells to other insults that activate the hepatic immune system and thereby exacerbate liver damage during acute inflammation.
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In vivo and in vitro experiments have demonstrated that PFAS exposure can lead to severe inflammation in organs, including the liver, kidneys, and nervous system.
“in vivo and in vitro experiments have demonstrated that PFAS exposure can lead to severe inflammation in organs, including the liver, kidneys, and nervous system”
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- Authors
- Qazi, M. R., Hassan, M., Nelson, B. D., DePierre, J. W., & Abedi-Valugerdi, M.
- Affiliations
- Stockholm University (SE)
- Karolinska University Hospital (SE)
- Venue
- Toxicology Letters
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 217
- Issue
- 1
- Pages
- 67-74
- ISSN
- 0378-4274 (ISSN-L)
- OpenAlex
- W2013251360
- Cited by
- 21
- References
- 37
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 6 · 2021: 2 · 2020: 1 · 2019: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 3
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- 3M Company (St. Paul, MN, USA)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- PFOS, concanavalin A, hepatotoxicity, dietary exposure, dose-response relationship, inflammatory cytokines, TNF-α, interferon-gamma, hepatomegaly
- MeSH terms
- Transaminases, Animals, Concanavalin A, Disease Models, Animal, Dose-Response Relationship, Drug, Environmental Pollutants, Fluorocarbons, Hepatomegaly, Immunologic Factors, Liver, Male, Mice, Inbred C57BL, Random Allocation, Time Factors, Cytokines, Apoptosis, Alkanesulfonic Acids, Disease Progression, Mice, DNA Fragmentation, Chemical and Drug Induced Liver Injury
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