Carbon tetrachloride toxicity as a model for studying free-radical mediated liver injury.
A single dose of CCl4 when administered to a rat produces centrilobular necrosis and fatty degeneration of the liver. These hepatotoxic effects of CCl4 are dependent upon its metabolic activation in the liver endoplasmic reticulum to reactive intermediates, including the trichloromethyl free radical. Positive identification of the formation of this free radical in vivo, in isolated liver cells and in microsomal suspensions in vitro has been achieved by e.s.r. spin-trapping techniques. The trichloromethyl radical has been found to be relatively unreactive in comparison with the secondarily derived peroxy radical CCl3O2., although each free radical species contributes significantly to the biological disturbances that occur. Major early perturbations produced to liver endoplasmic reticulum by exposure in vivo or in vitro to CCl4 include covalent binding and lipid peroxidation; studies of these processes occurring during CCl4 intoxication have uncovered a number of concepts of general relevance to free-radical mediated tissue injury. Lipid peroxidation produces a variety of substances that have high biological activities, including effects on cell division; many liver tumours have a much reduced rate of lipid peroxidation compared with normal liver. A discussion of this rather general feature of liver tumours is given in relation to the liver cell division that follows partial hepatectomy.
Slater
T F
TF
Cheeseman
K H
KH
Ingold
K U
KU
D000818:Animals; D001711:Biotransformation; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000209:etiology*; D002462:Cell Membrane / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced; D008113:Liver Neoplasms / Q000139:chemically induced*; D008954:Models, Biological
D005609:Free Radicals; D008054:Lipid Peroxides; D002251:Carbon Tetrachloride