The contribution of electrophilic and radicalic intermediates to phospholipid adducts formed by halomethanes in vivo

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Abstract
The different production of phosgene and free-radicals from CHCl3 and CCl4 was determined in vitro and in vivo, by measuring the regioselective binding of the two intermediates to phospholipid (PL) molecules. Results clearly indicated that this assay can be successfully used to selectively detect electrophilic and radicalic metabolites produced in vivo and selectively quantitate their adducts. The in vivo biotransformation of CCl4, similarly to the in vitro situation, resulted in the formation of radicals only, the contribution of phosgene to the structural damage of PL being negligible. These findings allowed us to rule out the hypothesis of substantial formation of radicalic intermediates from CHCl3 in phenobarbital (PB)-pretreated Sprague—Dawley (SD) rats, derived from in vitro data. While the role of reduced glutathione (GSH) in preventing COCl2-derived damages seems to be less important in vivo than in vitro, it is not possible to rule out the action of radical scavenging systems in decreasing the level of adducts with fatty acyl chains (FC) of PL measured in vivo.