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Complement activation is involved in the hepatic injury caused by high-dose exposure of mice to perfluorooctanoic acid
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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Number of Authors: 6
2015 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 129, no SI, 225-231 p.Article in journal (Refereed) Published
Abstract [en]

High-dose exposure of mice to perfluorooctanoate (PFOA) induces both hepatotoxicity and immunotoxicity. Here, we characterized the effects of TO-day dietary treatment with PFOA (0.002-0.02%, w/w) on the liver and complement system of male C57BL/6 mice. At all four doses, this compound caused hepatomegaly and reduced the serum level of triglycerides (an indicator for activation of the peroxisome proliferator-activated receptor-alpha (PPAR alpha)). At the highest dose (0.02%, w/w), this hepatomegaly was associated with the hepatic injury, as reflected in increased activity of alanine aminotranferase (ALAT) in the serum, severe hepatocyte hypertrophy and hepatocellular necrosis. PFOA-induced hepatic injury was associated with in vivo activation of the complement system as indicated by (i) significant attenuation of the serum activities of both the classical and alternative pathways; (ii) a marked reduction in the serum level of the complement factor 0; and (iii) deposition of the complement factor C3 fragment (C3a) in the hepatic parenchyma. PFOA did not activate the alternative pathway of complement in vitro. At doses lower than 0.02%, PFOA induced hepatocyte hypertrophy without causing liver injury or activating complement. These results reveal substantial involvement of activation of complement in the pathogenesis of PFOA-induced hepatotoxicity.

Place, publisher, year, edition, pages
2015. Vol. 129, no SI, 225-231 p.
Keyword [en]
Complement system, Complement factor C3, Hepatotoxicity, Liver injury, Perfluorooctanoate, Peroxisome proliferator-activated receptor alpha
National Category
Earth and Related Environmental Sciences
Identifiers
URN: urn:nbn:se:su:diva-117762DOI: 10.1016/j.chemosphere.2014.06.093ISI: 000353732600029OAI: oai:DiVA.org:su-117762DiVA: diva2:818512
Available from: 2015-06-09 Created: 2015-06-01 Last updated: 2017-12-04Bibliographically approved

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Botelho, Salomé CaladoDePierre, Joseph W.Abedi-Valugerdi, Manuchehr
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