کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2595964 1562364 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evaluation of hepatic and thyroid responses in male Sprague Dawley rats for up to eighty-four days following seven days of dietary exposure to potassium perfluorooctanesulfonate
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Evaluation of hepatic and thyroid responses in male Sprague Dawley rats for up to eighty-four days following seven days of dietary exposure to potassium perfluorooctanesulfonate
چکیده انگلیسی

In a prior 28-day dietary study in rats with 20 and 100 ppm K+PFOS, activation of PPARα and CAR/PXR were concluded to be etiological factors in K+PFOS-induced hepatomegaly and hepatic tumorigenesis. The objective of this study was to evaluate persistence/resolution of K+PFOS-induced, liver-related effects in male Sprague Dawley rats following a 7-day dietary exposure to K+PFOS at 20 or 100 ppm. Groups of 10 rats per treatment were observed on recovery Day(s) 1, 28, 56, and 84 following treatment. Changes consistent with hepatic PPARα and CAR/PXR activation noted on recovery Day 1 included: increased liver weight; decreased plasma cholesterol, alanine aminotransferase, and triglycerides; decreased liver DNA concentration and increased hepatocellular cytosolic CYP450 concentration; increased liver activity of acyl CoA oxidase, CYP4A, CYP2B, and CYP3A; increased liver proliferative index and decreased liver apoptotic index; decreased hepatocellular glycogen-induced vacuoles; increased centrilobular hepatocellular hypertrophy. Most effects resolved to control levels during recovery. Effects on plasma cholesterol, hepatocellular cytosolic CYP450 concentrations, liver apoptotic index, CYP3A, and centrilobular hepatocellular hypertrophy persisted through the end of the recovery period. Thyroid parameters (histology, apoptosis, and proliferation) were unaffected at all time points. Mean serum PFOS concentrations on recovery Day 1 were 39 and 140 μg/mL (20 ppm and 100 ppm K+PFOS, respectively), decreasing to 4 and 26 μg/mL by recovery Day 84. Thus, hepatic effects in male rats resulting from K+PFOS-induced activation of PPARα and CAR/PXR resolved slowly or were still present after 84-days following a 7-day dietary treatment, consistent with the slow elimination rate of PFOS.


► K+PFOS liver effects in rats were studied for 84-day after a 7-day dietary treatment.
► Thyroid histology, apoptosis, and proliferation were unaffected at all time points.
► Liver effects from activation of PPARα and CAR/PXR were evident on recovery Day 1
► Plasma ALT and AST values and histology indicated a lack of overt hepatotoxicity.
► Effects resolved slowly or were still present 84 days after dosing with K+PFOS.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 293, Issues 1–3, 11 March 2012, Pages 30–40
نویسندگان
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