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 metabolities covalently bound to hepatocyte protein was significantly enhanced in the presence of CCl₄.