Perfluoro-n-decanoic acid: induction of peroxisomal beta-oxidation by a fatty acid with dioxin-like toxicity

Abstract

Perfluoro-n-decanoic acid (PFDA) produces toxic effects in rodents similar to those caused by 2,3,7,8-tetrachloro-dibenzo-p-dioxin. A single, intraperitoneal dose (50 mg/kg) of PFDA to Sprague-Dawley rats caused disruption of the endoplasmic reticulum, mitochondrial swelling and increases in intracellular lipid droplets in hepatocytes similar to effects reported previously in dioxin toxicity. PFDA treatment led to large decreases in the activity of plasma membrane alkaline phosphodiesterase and mitochondrial cytochrome c oxidase without affecting lysosomal N-acetyl-beta-glucosaminidase, endoplasmic reticulum NADPH-cytochrome c reductase or peroxisomal catalase activities. PFDA treatment led to moderate peroxisome proliferation and to very large (20-40-fold) increases in the activity of fatty acyl-CoA oxidase, the rate-limiting enzyme in the peroxisomal system of fatty acid beta-oxidation.