Morphological adaptations of human liver peroxisomes in cholestasis.

Abstract

Part of the bile acid synthesis takes place in peroxisomes. An altered enterohepatic circulation of bile acids might influence peroxisomal beta-oxidation enzymes and peroxisomal morphology. We performed a morphological and morphometric investigation of peroxisomes in liver biopsy samples of eight patients with cholestasis of different origin: graft versus host reaction (n = 1), obstruction of the bile flow (n = 3), and drug-induced cholestatic hepatitis (n = 4). Peroxisomes were identified using catalase cytochemistry. They were regularly shaped and showed individual differences in electron density. A perinuclear distribution was observed in a variable number of hepatocytes in each sample. Morphometric analysis of peroxisomes revealed an increase in numerical density and surface density in all, and a decreased mean diameter in four liver samples. Based on previously obtained data in experimental animals, we hypothesize that the observed alterations in peroxisomal morphology indicate an enhanced metabolic activity of the enzymes in the peroxisomal matrix. Among them are enzymes involved in bile acid synthesis.