title: Sub-acute, moderate-dose, but not short-term, low-dose dietary pre-exposure of mice to perfluorooctanoate aggravates concanavalin A-induced hepatitis.
abstract: Exposure of mice to perfluorooctanoate (PFOA) evokes pronounced hepatomegaly along with significant alterations in both the histological structure and immune status of the liver. The present study was designed to evaluate the effects of this perfluorochemical on immune-mediated liver damage. In this connection, the influence of both sub-acute (10 days), moderate-dose (0.002% w/w=3±0.7mg/kg body weight/day) and short-term (28 days), low-dose (0.00005% w/w=70±2μg/kg body weight/day) dietary pretreatment with PFOA on the development of concanavalin A (Con A)-induced liver damage in mice was examined. With sub-acute, moderate, but not short-term, low-dose exposure, PFOA aggravated 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 aggravation was associated with significantly enhanced hepatic level of interleukin-6 (IL-6), but unaltered hepatic levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-4 (IL-4). Moreover, hepatic DNA fragmentation was not changed by sub-acute exposure to the moderate-dose. Our findings imply that exposure to PFOA may sensitize hepatic parenchymal cells to other toxicants that activate the hepatic immune system and thereby aggravate liver injury during acute inflammation.
authors: Department of Biochemistry and Biophysics, Arrhenius Laboratories for the Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden. mouqr@yahoo.com
authors: Mousumi Rahman
authors: MR
authors: Qazi
authors: Moustapha
authors: M
authors: Hassan
authors: B Dean
authors: BD
authors: Nelson
authors: Joseph W
authors: JW
authors: Depierre
authors: Manuchehr
authors: M
authors: Abedi-Valugerdi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002210:Caprylates / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D003208:Concanavalin A / Q000633:toxicity*; D016207:Cytokines / Q000097:blood; D053938:DNA Fragmentation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005466:Fluorocarbons / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D000637:Transaminases / Q000097:blood
chemical_list: D002210:Caprylates; D016207:Cytokines; D005466:Fluorocarbons; D003208:Concanavalin A; C023036:perfluorooctanoic acid; D000637:Transaminases