Sub-acute,moderate-dose,but not short-term,low-dose dietary pre-exposure of mice to perfluorooctanoate aggravates concanavalin A-induced hepatitis |
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Authors: | Mousumi Rahman Qazi Moustapha Hassan B. Dean Nelson Joseph W. DePierre Manuchehr Abedi-Valugerdi |
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Affiliation: | 1. Department of Biochemistry and Biophysics, Arrhenius Laboratories for the Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden;2. Experimental Cancer Medicine, Clinical Research Center, Novum, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden;3. ImmunoBioTox (IBT) AB, 16954 Solna, Sweden |
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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 ± 0.7 mg/kg body weight/day) and short-term (28 days), low-dose (0.00005% w/w = 70 ± 2 μg/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. |
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Keywords: | ALT, alanine aminotransferase AST, aspartate aminotransferase Con A, concanavalin A IFN-γ, interferon-gamma IL-4, interleukin-4 IL-6, interlukin-6 PFOA, perfluorooctanoate PFAAs, perfluoroalkyl acids TNF-α, tumor necrosis factor-alpha |
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