Hepatic Peroxisome Proliferation: Induction by Two Novel Compounds Structurally Unrelated to Clofibrate

Abstract

Two hypolipidemic compounds [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid, and 2-chloro-5-(3,5-dimethylpiperidinosulfonyl)benzoic acid (tibric acid) greatly increased the number of peroxisomes (microbodies) in liver cells of rats and mice. This augmented peroxisome population was accompanied by significant elevation of liver catalase activity. These two hypolipidemic peroxisome proliferators are structurally different from ethyl α- p -chlorophenozyisobutyrate (clofibrate) and other hypolipidemic, aryloxyisobutyrate derivatives which cause hepatic peroxisome proliferation. Induction of peroxisome proliferation by these structurally unrelated hypolipidemic compounds suggests a possible relation between hepatic peroxisome proliferation and hypolipidemia.