Abstract
Swelling with nonlipid cytoplasmic vacuolation of diffusely distributed hepatocytes is seen consistently after mild acute and subacute liver injury. Several lines of evidence point to the possibility that this change may reflect a cellular adaptation beneficial to the host, rather than a degenerative change. The nature and significance of this morphological manifestation were tested in batches of albino rats given small doses of a variety of hepatotoxins, some of which were subsequently challenged with a large highly necrogenic dose of carbon tetrachloride (CCl4). Morphological and biochemical investigations showed that cytoplasmic vacuolation of liver cells following low doses of toxins was due to excess accumulation of glycogen, predominantly of the monoparticulate form. These cells lacked features of degeneration or regeneration and were much less susceptible to injury by the large dose CCl4, as assessed by structural and serum enzyme analyses. This tolerance to toxic damage seemed to be associated with excess accumulation of intracellular glycogen. We conclude from these and other observations on animal and human livers that many of the vacuolated hepatocytes seen in liver injury are cells adaptively altered to resist further insult rather than cells undergoing hydropic degeneration, as is commonly believed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Al Adnani MS (1989) Differential immunohistochemical localization of cytokeratins and collagen types I and II in experimentally induced cirrhosis. J Pathol 159:151–158
Babcock MB, Cardell RR (1974) Hepatic glycogen patterns in fasted and fed rats. Am J Anat 140:229–239
Bannasch P (1968) The cytoplasm of hepatocytes during carcinogenesis. Recent Results Cancer Res 19:1–105
Bannasch P, Mayer D, Hacker H (1980) Hepatocellular glycogenesis and hepatocarcinogenesis. Biochim Biophys Acta 605:217–245
Bucher NLR (1963) Regeneration of mammalian liver. Int Rev Cytol 15:245–260
Cardell RR, Cardell EL (1990) Hetrogeneity of glycogen distribution in hepatocytes. J Electron Microsc Technol 14:126–139
Carr BI (1987) Pleiotropic drug resistance in hepatocytes induced by carcinogens administered to rats. Cancer Res 47:5577–5583
Carr BI, Laishes BA (1981) Carcinogen-induced drug resistance in rat hepatocytes. Cancer Res 41:1715–1719
Chopra P, Roy S, Ramalingaswami V, Nayak NC (1972) Mechanism of carbon tetrachloride hepatotoxicity. An in vivo study of its molecular basis in rats and monkeys. Lab Invest 26:716–727
Das PK, Chopra P, Nayak NC (1974) Hepatocellular tolerance to carbon tetrachloride induced injury in the rat: a study of its nature and possible mode of evolution. Exp Mol Pathol 21:218–236
Farber E (1963) The sequential analysis of cancer development. Adv Cancer Res 7:383–474
Farber E, Sarma DS (1987) Hepatocarcinogenesis: a dynamic cellular perspective. Lab Invest 56:4–22
Farber E, Parker S, Gruenstein M (1976) The resistance of putative premalignant liver cell populations, hyperplastic nodules to the acute cytotoxic effects of some hepatocarcinogens. Cancer Res 36:3879–3887
Farber JL, El-Mofty SK (1975) The biochemical pathology of liver cell necrosis. Am J Pathol 81:237–245
Gooding PE, Chayen J, Sawyer B, et al (1978) Cytochrome P450 distribution in rat liver and the effect of sodium phenobarbitone administration. Chem Biol Interact 20:299–310
Haddow A (1935) Influence of certain polycyclic hydrocarbons on the growth of the Jensen rat sarcoma. Nature (Lond) 136:868–869
Hansen J, Cherwitz DL, Allen JI (1994) The role of tumour necrosis factor-α in acute endotoxin-induced hepatotoxicity in ethanol-fed rats. Hepatology 20:461–474
Harris L, Morris LE, Farber E (1989) Protective value of a liver initiation-promotion regimen against the lethal effect of carbontetrachloride in rats. Lab Invest 61:467–470
Kalengayi MMR, Ronchi G, Desmet VJ (1975) Histochemistry of gamma-glutamyl transpeptidase in rat liver during aflatoxin B1 induced carcinogenesis. J Natl Cancer Inst 55:579–584
Keppler D, Decker K (1974) Glycogen determination with amyloglucosidase. In: Bergmeyer HU (ed) Methods of enzymatic analysis, vol 4. Verlag Chemie, Weinheim New York, pp 1127–1131
Lane BP, Europa DL (1968) Differential staining of ultrathin sections of epon embedded tissues for light microscopy. J Histochem Cytochem 13:579–584
Leevy CH, Hollister RM, Schimd R, Richard AM, Charles SD (1959) Liver regeneration in experimental carbon tetrachloride intoxication. Proc Soc Exp Biol Med 102:672–675
MacNider WDB (1936) A study of the acquired resistance of fixed tissue cells morphologically altered through processes of repair. I. The liver injury induced by uranium nitrate. A consideration of the type of epithelial repair which imparts to the liver resistance against subsequent uranium intoxications. J Pharmacol Exp Ther 56:359–372
MacNider WDB (1937) A study of the acquired resistance of fixed tissue cells morphologically altered through processes of repair. IV. Concerning the persistence of an acquired type of atypical liver cell with observations on the resistance of such cells to the toxic action of chloroform. J Pharmacol Exp Ther 59:393–398
Manga A, Chopra P, Nayak NC (1983) Cellular evolution of hepatic cancer in rats. Indian J Med Res 78 [Suppl]:141–154
Mathur M, Singhal V, Nayak NC (1983) Variability in acute aflatoxin B induced liver injury. Indian J Med Res 77:668–678
Nayak NC (1981) Bridging necrosis of the liver. Trop Gastroenterol 2:1–3
Nayak NC (1983) Morphological changes in the liver in subacute hepatic failure. In: Tandon BN (ed) Subacute hepatic failure. Chakra, New Dehli, pp 21–23
Popper H (1988) Degeneration and death. In: Arias M, Jacobi WB, Popper H, et al. (eds) The liver biology and pathology. Raven Press, New York, pp 1087–1105
Recknagel RO, Glende EA (1973) Carbontetrachloride hepatotoxicity: an example of lethal cleavage. Crit Rev Toxicol 2:263–270
Revel JP, Napolitano L, Fawcett DW (1960) Identification of glycogen in electron micrographs of thin tissue sections. J Biophys Biochem Cytol 8:575–589
Rizvi TA, Mathur M, Nayak NC (1987) The effect of protein calorie malnutrition and cell replication on aflatoxin B1-induced hepatocarcinogenesis. J Natl Cancer Inst 79:817–830
Rizvi TA, Mathur M, Nayak NC (1989) Enhancement of aflatoxin B1-induced hepatocarcinogenesis in rats by partial hepatectomy. Virchows Arch [B] 56:345–350
Sasaki Y, Hayashi N, Morita Y, Ito T, Kasahara A, Fusamuto H, Kamada T (1989) Cellular analysis of c-Ha-ras gene expression in rat liver after CCl4 administration. Hepatology 10:494–500
Scherer E, Emmelot P (1976) Kinetics of induction and growth of enzyme-deficient islands involved in hepatocarcinogenesis. Cancer Res 36:2544–2554
Sherer E, Hoffman M, Emmelot P, Friedrich-Freksa H (1972) Quantitative study of foci of altered liver cells in the rat by a single dose of diethylnitrosamine and partial hepatectomy: J Natl Cancer Inst 49:98–106
Scheuer PJ (1987) Viral hepatitis. In: MacSween RNM, Anthony PJ, Scheur PJ (eds) Pathology of the liver, 2nd edn. Churchill Livingstone, London, pp 202–223
Wachstein M, Meisel E (1956) On the histochemical demonstration of glucose-6-phosphatase. J Histochem Cytochem 4:592–598
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nayak, N.C., Sathar, S.A., Mughal, S. et al. The nature and significance of liver cell vacuolation following hepatocellular injury — an analysis based on observations on rats rendered tolerant to hepatotoxic damage. Vichows Archiv A Pathol Anat 428, 353–365 (1996). https://doi.org/10.1007/BF00202202
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00202202