Dietary exposure to perfluorooctanoate or perfluorooctane sulfonate induces hypertrophy in centrilobular hepatocytes and alters the hepatic immune status in mice.
It is well established that exposure of mice to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) induces hepatomegaly and, concurrently, immunotoxicity. However, the effects of these perfluorochemicals on the histology and immune status of the liver have not been yet investigated and we have examined these issues here. Dietary treatment of male C57BL/6 mice with 0.002% (w/w) PFOA or 0.005% (w/w) PFOS for 10 days resulted in significant reductions in serum levels of cholesterol and triglycerides, a moderate increase in the serum activity of alkaline phosphatase (ALP) and hepatomegaly, without affecting other immune organs. This hepatomegaly was associated with marked hypertrophy of the centrilobular hepatocytes, with elevated numbers of cytoplasmic acidophilic granules and occasional mitosis. Furthermore, dietary exposure to PFOA or PFOS altered the hepatic immune status: whereas exposure to PFOA enhanced the numbers of total, as well as of phenotypically distinct subpopulations of intrahepatic immune cells (IHIC), and in particular the presumptive erythrocyte progenitor cells, treatment with PFOS enhanced only the numbers of hepatic cells that appear immunophenotypically to be erythrocyte progenitors, without affecting other types of IHIC. In addition, exposure to these compounds attenuated hepatic levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-4 (IL-4). Furthermore, the exposed animals exhibited a significant increase in hepatic levels of erythropoietin, a hormone required for erythropoiesis. Thus, in mice, PFOA- and PFOS-induced hepatomegaly is associated with significant alterations in hepatic histophysiology and immune status, as well as induction of hepatic erythropoiesis.
Qazi
Mousumi Rahman
MR
Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Abedi
Mohammad R
MR
Nelson
B Dean
BD
DePierre
Joseph W
JW
Abedi-Valugerdi
Manuchehr
M
D000469:Alkaline Phosphatase / Q000097:blood; D017738:Alkanesulfonic Acids / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002210:Caprylates / Q000008:administration & dosage / Q000633:toxicity*; D002784:Cholesterol / Q000097:blood; D004032:Diet / Q000009:adverse effects; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D004921:Erythropoietin / Q000032:analysis; D005466:Fluorocarbons / Q000008:administration & dosage / Q000633:toxicity*; D006529:Hepatomegaly / Q000139:chemically induced* / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000187:drug effects / Q000276:immunology; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D017738:Alkanesulfonic Acids; D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D015847:Interleukin-4; D007371:Interferon-gamma; C023036:perfluorooctanoic acid; D002784:Cholesterol; C076994:perfluorooctane sulfonic acid; D000469:Alkaline Phosphatase