EFFECT OF THE PEROXISOME PROLIFERATOR PERFLUORO-N-DECANOIC ACID ON GLUCOSE-TRANSPORT IN THE ISOLATED-PERFUSED RAT-LIVER

The perfluorinated carboxylic acid, perfluoro-n-decanoic acid (PFDA), is a known peroxisome proliferator which displays toxicity in rodents. Using a paired-tracer first-pass extraction technique, the effect of PFDA on hepatic glucose transport was determined in the isolated perfu sed rat liver. In brief, livers isolated from PFDA-treated and control rats on day 5 posttreatment were administered the radiolabeled glucos e analog, 3-O-[C-14]methyl-D-glucose ([C-14]3-O-MG) in addition to [fr uctose-1-H-3(N)]sucrose ([H-3]sucrose), which served as a measure of e xtracellular volume. Hepatic glucose transport was calculated from the change in the ratio [C-14]3-O-MG/[H-3]sucrose during passage through the liver. Data from this study indicate that PFDA inhibits hepatic gl ucose transport. Percent hepatic glucose extraction is 1.8-fold greate r in controls than in PFDA-treated rats. No significant difference in lactate dehydrogenase levels was observed in the liver perfusate from PFDA-treated and control rats. This suggests that the difference in pe rcent glucose extraction between PFDA-treated and control groups is sp ecifically due to the PFDA treatment and is not attributed to differen ces in liver viability between groups. Although the exact mechanism fo r this inhibition in hepatic glucose transport is not known, it is hyp othesized that PFDA may have a major impact on membrane structure/func tion which, in turn, may alter glucose transport.