Summary
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 ρ-nitroanisoleO-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 ρ-nitroanisoleO-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 ρ-nitroanisoleO-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.
Similar content being viewed by others
References
Letteri JM, et al: A diphenylhydantoin metabolism in uremia. New Engl J Med 285: 648, 1971
Ordar-Cederlof I, et al: Kinetics of diphenylhydantoin in uremic patients: Consequences of decreased plasma protein binding. Euro J Clin Pharmacol 7:31, 1974
Thompson FD, et al: Pharmacodynamics of propranolol in renal failure. Brit Med J 2: 434, 1972
Held H, et al: Elimination and serum protein binding of phenylbutazone in patients with renal insufficiency. Clin Nephrol 6: 388, 1976
Lichter M, et al: The metabolism of antipyrine in patients with chronic renal failure. J Pharmacol Exp Ther l87:612, 1973
Maddocks JL, et al: The plasma half-life of antipyrine in chronic uremic and normal subjects. Brit J Clin Pharmacol 2: 339, 1975
Kawata S, et al: Morphological changes of the liver in uremic patients treated with chronic hemodialysis. Laparoscopic observations and light and electronmicroscopic studies. Gastroenterol Jpn 15: 212, 1980
Black M, et al: Effect of chronic renal failure in rats on structure and function of the hepatic endoplasmic reticulum. Exp Mol Pathol 27: 377, 1977
Schaffner F, et al: Cholestasis is the result of hypoactive hypertrophic smooth endoplasmic reticulum in thehepatocyte. Lancet 2: 355, 1969
Weibel ER, et al: Correlated morphometric and biochemical studies on the liver cell. I. Morphometric model, stereologic methods and normal morphometric data for rat liver. J Cell Biol 42: 68, 1969
Weibel ER, et al: Practical stereological methods for morphometric cytology. J Cell Biol 30: 23, 1966
Omura T, et al: The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239: 2370, 1964
Sugiyama T, et al: NADH and NADPH-dependent reconstituted ρ-nitroanisole O-demethylase system containing cytochrome P-450 with high affinity for cytochrome b5. J Biochem 87: 1457, 1980
Lowry OH, et al: Protein measurement with Folin phenol reagent. J Biol Chem 193: 265, 1951
Oshino N, et al: Electron transfer mechanism associated with fatty acid desaturation catalyzed by liver microsomes. Biochem Biophys Acta 128: 13, 1966
Shimakata T, et al: Reconstitution of hepatic microsomal stearyl Co A desaturase system from solubilized components. J Biochem 72: 1163, 1972
Fleischmann R, et al: Micromethod for the preparation of a microsomal fraction from rat and human liver by differential sedimentation. Biochem Biophys Res Commun 62: 289, 1975
Miyake Y, et al: Abnormal microsomal and electron transport in Morris hepatoma. J Biol Chem 249: 1980, 1974
Blum M, et al: Liver enlargement in long-term hemodialysis patients. Arch Intern Med 140: 343, 1980
Raisfeld IH, et al: The effect of 3-amino-l,2,4-triazole on the phenobarbital induced formation of hepatic microsomal membranes. Mol Pharmacol 6: 231, 1969
Hutterer F, et al: Hepatocellular adaptation and injury. Structural and biochemical changes following dieldrin and methyl butter yellow. Lab Invest 20: 455, 1969
Baron J, et al: Effect of 3-amino-l,2,4-triazole on the stimulation of hepatic microsomal heme synthesis and induction of hepatic microsomal oxidases produced by phenobarbital. Mol Pharmacol 5: 10, 1969
Denk H: Die chemische Struktur des endoplasmischen Retikulumus und die Funktion des Mikrosomalen En zymsystems der Leberzelle der Ratte bei Experimenteller Cholestase. Pathol Eur 7: 43, 1972
Denk H: Hepatic microsomal enzymes and their alterations in pathologic conditions, in “Progress in Liver Disease” Vol 6, by Popper H, Schaffner F Grune & Stratton, New York, 1979, p 263
Denk H, et al: Turnover of hepatic cytochrome P-450 in experimental cholestasis. Exp Mol Pathol 19: 241, 1973
Mackinnon AM, et al: Reduced synthesis of hepatic microsomal cytochrome P-450 in the bile duct ligated rat. Biochem Biophys Res Commun 56: 437, 1974
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kawata, S., Seki, K., Shinji, Y. et al. Hypertrophic and hypoactive smooth endoplasmic reticulum in hepatocytes of uremic patients. A morphometric and biochemical study. Gastroenterol Jpn 17, 192–200 (1982). https://doi.org/10.1007/BF02775995
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02775995