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Short term exposure to perluoroalkyl acids causes increase of hepatic lipid and triglyceride in conjunction with liver hypertrophy
Citation:
Das, K., C. Wood, Mitch Rosen, C. Lau, AND B. Abbott. Short term exposure to perluoroalkyl acids causes increase of hepatic lipid and triglyceride in conjunction with liver hypertrophy. Presented at Society of Toxicology meeting, March 10 - 14, 2013.
Impact/Purpose:
This abstract will be presented at the Society of Toxicology Meeting, March 10-14, 2013, San Antonio, TX
Description:
ABSTRACT BODY: Persistent presence of perfluoroalkyl acids (PFAAs) in the environment is due to extensive use of industrial and consumer products. These chemicals activate peroxisome proliferatoractivated receptor-alpha (PPARa) in liver and after lipid metabolism. The current study was designed to evaluate liver toxicity of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHXS), and periluorophosphonoic acid (PFPA), with emphasis on hepatocellular hypertrophy and steatosis. SVI 29 wild-type (VVT) and PPARa-null (Null) adult male mice were dosed for 7 days with vehicle, PFOA, PFNA, PFHxS (10 mg/kg), and PFPA (20 mg/kg); and WY14643 (50 mg/kg) was a positive control. Mice were killed 24 h after the last treatment. Liver samples were collected for biochemical analysis of triglyceride (TG) and DNA content. Frozen 6 pm sections of liver were stained with Oil Red 0 for lipid and used for morphometnc analysis. Liver weights were elevated in both WT and Null mice in all of the treatment groups, except in Null mice of the PFPA and WY groups. Morphometric analysis revealed an increase in cell size in WT and Null livers exposed to PFOA, PFNA, PFHXS or PFPA, except for the PFPA and WY groups in Null mice. This pattern of change is consistent with the reduced DNA content per mg liver. In the Oil Red 0 stained sections, WT liver showed increased lipid accumulation in all treatment groups; whereas in Null livers, this was seen only after PFNA and PFHxS treatment. Similarly, elevated TG level was found in PFAA-exposed WT but not in WY-exposed mice, and increased TG was seen in Null mice only after PFNA treatment. Null livers had more lipid and TG than WT livers, both in control and treated mice. These results indicate that PFAAs induce liver hypertrophy and steatosis in WT; and the involvement of PPARa is suggested by observations in Null mice. (This abstract does not necessarily reflect US EPA policy.)