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.
CXR Biosciences Ltd, Dundee DD1 5JJ, Scotland, UK. cliffelcombe [at] cxrbiosciences.com
Toxicology. 2012 Mar;293(1-3):30-40
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