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Zeitschrift für Naturforschung C

A Journal of Biosciences

Editor-in-Chief: Seibel, Jürgen

Editorial Board: Aigner , Achim / Boland, Wilhelm / Bornscheuer, Uwe / Hoffmann, Klaus

IMPACT FACTOR 2017: 0.882
5-year IMPACT FACTOR: 0.912

CiteScore 2018: 0.99

SCImago Journal Rank (SJR) 2018: 0.246
Source Normalized Impact per Paper (SNIP) 2018: 0.437

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Volume 56, Issue 7-8


Mechanism of Carbon Tetrachloride-Induced Hepatotoxicity. Hepatocellular Damage by Reactive Carbon Tetrachloride Metabolites

Meinrad Boll
  • Corresponding author
  • Institute of Toxicology, GSF - National Research Center for Environment and Health, München, Ingolstädter Landstrasse, 85764 Neuherberg, Germany.
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/ W. D. Lutz
  • Institute of Toxicology, GSF - National Research Center for Environment and Health, München, Ingolstädter Landstrasse, 85764 Neuherberg, Germany.
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/ Eberhard Becker
  • Institute of Toxicology, GSF - National Research Center for Environment and Health, München, Ingolstädter Landstrasse, 85764 Neuherberg, Germany.
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/ Andreas Stampfl
  • Institute of Toxicology, GSF - National Research Center for Environment and Health, München, Ingolstädter Landstrasse, 85764 Neuherberg, Germany.
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Published Online: 2014-06-02 | DOI: https://doi.org/10.1515/znc-2001-7-826

CCl4-induced liver damage was modeled in monolayer cultures of rat primary hepatocytes with a focus on involvement of covalent binding of CCl4 metabolites to cell components and/or peroxidative damage as the cause of injury.

(1) Covalent binding of 14C-labeled metabolites was detected in hepatocytes immediately after exposure to CCl4. (2) Low oxygen partial pressure increased the reductive metabolism of CCl4 and thus covalent binding. (3) [14C]-CCl4 was bound to lipids and to proteins throughout subcellular fractions. Binding occurred preferentially to triacylglycerols and phospholipids, with phosphatidylcholine containing the highest amount of label. (4) The lipid peroxidation potency of CCl4 revealed subtle differences compared to other peroxidative substances, viz., ADP-Fe3+ and cumol hydroperoxide, respectively. (5) CCl4, but not the other peroxidative substances, decreased the rate of triacylglycerol secretion as very low density lipoproteins. (6) The anti-oxidant vitamin E (α-tocopherol) blocked lipid peroxidation, but not covalent binding, and secretion of lipoproteins remained inhibited. (7) The radical scavenger piperonyl butoxide prevented CCl4-induced lipid peroxidation as well as covalent bind­ing of CCI4 metabolites to cell components, and also restored lipoprotein metabolism.

The results confirm that covalent binding of the CCl3* radical to cell components initiates the inhibition of lipoprotein secretion and thus steatosis, whereas reaction with oxygen, to form CCI3*-OO*, initiates lipid peroxidation. The two processes are independent of each other, and the extent to which either process occurs depends on partial oxygen pressure. The former process may result in adduct formation and, ultimately, cancer initiation, whereas the latter results in loss of calcium homeostasis and, ultimately, apoptosis and cell death

: Liver Damage; Carbon Tetrachloride; Peroxidation

About the article

Received: 2001-03-28

Published Online: 2014-06-02

Published in Print: 2001-08-01

Citation Information: Zeitschrift für Naturforschung C, Volume 56, Issue 7-8, Pages 649–659, ISSN (Online) 1865-7125, ISSN (Print) 0939-5075, DOI: https://doi.org/10.1515/znc-2001-7-826.

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© 1946 – 2014: Verlag der Zeitschrift für Naturforschung. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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