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Complement activati...
Complement activation is involved in the hepatic injury caused by high-dose exposure of mice to perfluorooctanoic acid
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- Calado Botelho, Salomé (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Saghafian, Maryam (author)
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- Pavlova, Svetlana (author)
- Karolinska Institutet
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- Hassan, Moustapha (author)
- Karolinska Institutet
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- DePierre, Joseph W. (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Abedi-Valugerdi, Manuchehr (author)
- Karolinska Institutet,Stockholms universitet,Institutionen för biokemi och biofysik,Karolinska University Hospital, Sweden; ImmunoBioTox (IBT) AB, Sweden
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- English.
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In: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 129:SI, s. 225-231
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- Complement system
- Complement factor C3
- Hepatotoxicity
- Liver injury
- Perfluorooctanoate
- Peroxisome proliferator-activated receptor alpha
Publication and Content Type
- ref (subject category)
- art (subject category)
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