Complement activation is involved in the hepatic injury caused by high-dose exposure of mice to perfluorooctanoic acid
| Autor: | Manuchehr Abedi-Valugerdi, Svetlana Pavlova, Joseph W. DePierre, Moustapha Hassan, Maryam Saghafian, Salomé Calado Botelho |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Environmental Engineering Health Toxicology and Mutagenesis Complement factor I Muscle hypertrophy Mice In vivo Internal medicine medicine Animals Environmental Chemistry PPAR alpha Complement Activation Triglycerides Liver injury Fluorocarbons Chemistry Public Health Environmental and Occupational Health Complement C3 General Medicine General Chemistry medicine.disease Pollution Complement system Mice Inbred C57BL Endocrinology medicine.anatomical_structure Liver Hepatocyte Immunology Hepatocytes Alternative complement pathway Peroxisome proliferator-activated receptor alpha Caprylates |
| Zdroj: | Chemosphere. 129:225-231 |
| ISSN: | 0045-6535 |
| DOI: | 10.1016/j.chemosphere.2014.06.093 |
| Popis: | High-dose exposure of mice to perfluorooctanoate (PFOA) induces both hepatotoxicity and immunotoxicity. Here, we characterized the effects of 10-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 (PPARα)). 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 C3; 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. |
| Databáze: | OpenAIRE |
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