title: 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.
authors.affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratories for the Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden. mouqr@yahoo.com
authors.forename: Mousumi Rahman
authors.initials: MR
authors.lastname: Qazi
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hassan
authors.forename: B Dean
authors.initials: BD
authors.lastname: Nelson
authors.forename: Joseph W
authors.initials: JW
authors.lastname: DePierre
authors.forename: Manuchehr
authors.initials: M
authors.lastname: Abedi-Valugerdi
mesh_terms: D017738:Alkanesulfonic Acids / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003208:Concanavalin A; D016207:Cytokines / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage* / Q000633:toxicity; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000633:toxicity; D006529:Hepatomegaly / Q000209:etiology; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D013997:Time Factors; D000637:Transaminases / Q000097:blood
chemical_list: D017738:Alkanesulfonic Acids; D016207:Cytokines; D004785:Environmental Pollutants; D005466:Fluorocarbons; D007155:Immunologic Factors; D003208:Concanavalin A; C076994:perfluorooctane sulfonic acid; D000637:Transaminases