Change of liver metabolism of 1,2-dibromoethane during simultaneous treatment with carbon tetrachloride.
The combination of carbon tetrachloride (CCl4) and 1,2-dibromoethane (DBE) in isolated rat hepatocytes led to a significant potentiation of both lipid peroxidation and of plasma membrane damage observed after a single treatment with CCl4. Such a synergistic effect appeared to be related to the CCl4-induced shift of DBE metabolism from the cytosolic conjugation with glutathione towards the microsomal transformation into toxic intermediates. In fact, CCl4 significantly inactivated hepatocyte total GSH-transferase, i.e. the DBE detoxification pathway. Furthermore, while the microsomal metabolism of CCl4 was not affected by the simultaneous presence of DBE, the amount of DBE reactive metabolites covalently bound to hepatocyte protein was significantly enhanced in the presence of CCl4.
Chiarpotto
E
E
Department of Experimental Medicine and Oncology, University of Torino, Italy.
Biasi
F
F
Aragno
M
M
Scavazza
A
A
Danni
O
O
Albano
E
E
Poli
G
G
D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D015946:Ethylene Dibromide / Q000493:pharmacokinetics*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008658:Inactivation, Metabolic; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000494:pharmacology
D008563:Membrane Lipids; D014810:Vitamin E; D015946:Ethylene Dibromide; D002251:Carbon Tetrachloride; D005982:Glutathione Transferase