Carbon tetrachloride and bromotrichloromethane toxicity: Dual role of covalent binding of metabolic cleavage products and lipid peroxidation in depression of microsomal calcium sequestration

We have investigated the importance of covalent binding and lipid peroxidation on the depression of microsomal calcium sequestration associated with in vitro metabolism of 14CCl 4. Studies with CBrCl 3 are also reported. In aerobic systems, promethazine was used to block lipid peroxidation, measured as malondialdehyde (MDA) generation. Effects of low levels of lipid peroxidation were tested in Fe 2+ -supplemented systems free of halogenated hydrocarbons. The results indicate that microsomal calcium sequestration can be depressed significantly by metabolism of either CCl 4 or CBrCl 3 in the absence of MDA generation, or by lipid peroxidation occurring in the absence of halogenated hydrocarbons.