Hypertrophic and hypoactive smooth endoplasmic reticulum in hepatocytes uremic patients. A morphometric and biochemical study

Abstract

Morphometric analysis of the hepatic endoplasmic reticulum and assays of drug-metabolizing enzymes in microsomes prepared from needle biopsy specimens were performed with samples from uremic patients on chronic hemodialysis and normal controls. The smooth endoplasmic reticulum (SER) morphometrically increased in the uremic patients, whereas the cytochrome P-450 content and the activity of p-nitroanisole O-demethylase per mg microsomal protein decreased in the uremic patients. This condition of SER corresponds to that of the so-called hypoactive hypertrophic smooth endoplasmic reticulum, which could suggest lower activity of hepatic microsomal drug oxidation in uremic patients. On the other hand, the P-450 content and the activity of p-nitroanisole O-demethylase per g liver were not significantly different between the uremic and the normal subjects. This seems to indicate that the capacity of drug oxidation is retained in whole livers of uremic patients. However, since some patients in this study showed markedly low activity of p-nitroanisole O-demethylase per mg microsomal protein and per g liver, lipophilic drugs metabolized in the liver as well as hydrophilic ones eliminated by the kidney should be carefully administered to uremic patients.