Perfluorooctane Sulfonate-Induced Hepatic Steatosis in Male Sprague Dawley Rats Is Not Attenuated by Dietary Choline Supplementation.

Autor: Bagley BD; Medical Department, 3M Company, St. Paul, Minnesota 55144., Chang SC; Medical Department, 3M Company, St. Paul, Minnesota 55144., Ehresman DJ; Medical Department, 3M Company, St. Paul, Minnesota 55144., Eveland A; Medical Department, 3M Company, St. Paul, Minnesota 55144., Zitzow JD; Medical Department, 3M Company, St. Paul, Minnesota 55144., Parker GA; Charles River Laboratories, Durham, North Carolina 27703., Peters JM; Department of Veterinary and Biomedical Sciences and The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania 16802., Wallace KB; Department of Biomedical Sciences, University of Minnesota Duluth Medical School, Duluth, Minnesota 55812., Butenhoff JL; SaluTox LLC, Lake Elmo, Minnesota 55042.
Jazyk: angličtina
Zdroj: Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2017 Dec 01; Vol. 160 (2), pp. 284-298.
DOI: 10.1093/toxsci/kfx185
Abstrakt: Perfluorooctane sulfonate (PFOS) is an environmentally persistent chemical. Dietary 100 ppm PFOS fed to male mice and rats for 4 weeks caused hepatic steatosis through an unknown mechanism. Choline deficient diets can cause hepatic steatosis. A hepatic choline:PFOS ion complex was hypothesized to cause this effect in mice. This study tested whether dietary choline supplementation attenuates PFOS-induced hepatic steatosis in rats. Sprague Dawley rats (12/sex/group) were fed control, choline supplemented (CS), 100 ppm PFOS, or 100 ppm PFOS + CS diets for 3 weeks. Male rats fed both PFOS-containing diets had decreased serum cholesterol and triglycerides (TGs) on days 9, 16, and/or 23 and increased hepatic free fatty acids and TG (ie, steatosis). Female rats fed both PFOS diets had decreased serum cholesterol on days 9 and 16 and decreased hepatic free fatty acid and TG at termination (ie, no steatosis). Liver PFOS concentrations were similar for both sexes. Liver choline concentrations were increased in male rats fed PFOS (±CS), but the increase was lower in the PFOS + CS group. Female liver choline concentrations were not altered by any diet. These findings demonstrate a clear sex-related difference in PFOS-induced hepatic steatosis in the rat. Additional evaluated mechanisms (ie, nuclear receptor activation, mRNA upregulation, and choline kinase activity inhibition) did not appear to be involved in the hepatic steatosis. Dietary PFOS (100 ppm) induced hepatic steatosis in male, but not female, rats that was not attenuated by choline supplementation. The mechanism of lipid accumulation and the sex-related differences warrant further investigation.
(© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
Databáze: MEDLINE