Mechanisms of carbon tetrachloride hepatotoxicity

Pathol Immunopathol Res. 1989;8(2):104-12. doi: 10.1159/000157141.

Abstract

CCI4 has long served as a model compound for study of hepatotoxicity. While its simple chemical structure held the allure of a simple mechanism of action, decades of study have disclosed a complex series of responses. Significant early damage following CCI4 administration includes: (1) A number of alterations affecting Ca2+ homeostasis, which conspire to redistribute cellular Ca2+ from endoplasmic reticulum and mitochondria to cytosol, and (2) hypomethylation of ribosomal RNA, which disrupts protein synthesis. The genesis of the injury in vivo appears to encompass early 'metabolism-dependent' effects (which appear to be largely independent of CCI4 concentration at the levels studied) and later 'metabolism-independent' effects, which parallel CCI4 concentration. The inability of injured hepatocytes to respond anabolically to early damage may be a critical feature in CCI4 hepatotoxicity.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / metabolism
  • Carbon Tetrachloride / toxicity*
  • Chemical and Drug Induced Liver Injury*
  • Cytochrome P-450 Enzyme System / metabolism
  • Homeostasis
  • Humans
  • Liver / drug effects*
  • Proteins / metabolism
  • RNA, Ribosomal / metabolism
  • Time Factors

Substances

  • Proteins
  • RNA, Ribosomal
  • Cytochrome P-450 Enzyme System
  • Carbon Tetrachloride
  • Calcium