Promethazine inhibits theformation ofaldehydic products oflipid peroxidation butnotcovalent binding resulting fromtheexposure ofratliver fractions toCC14

Promethazine isknowntohaveprotective activity inrelation toCCl4-induced liver necrosis-. This hepatoprotective property hasbeeninvestigated withregard tothefree radical scavenging andantioxidant properties ofpromethazine using isolated hepatocytes andm-icrosomal suspensions. CC14isactivated inboth systems tofree radical metabolites that bindcovalently tolipid andprotein, andinitiate lipid peroxidation. A large numberofcarbonyl products isproduced during CCl4-induced lipid peroxidation; promethazine strongly inhibits theproduction ofallclasses ofcarbonyl compounds inbothmicrosomal suspensions and isolated hepatocytes. Incontrast, promethazine isa veryweakinhibitor ofthecovalent binding of metabolites ofCC14. Weconclude that promethazine acts byscavenging thetrichloromethylperoxyl radical andlipid peroxyl radicals, andisaweakscavenger ofthetrichloromethyl radical. Thesedata, when considered together withthehepatoprotective effects ofpromethazine, suggest that lipid peroxidation isof relatively moreimportance thancovalent binding inthepathogenesis ofCCl4-induced liver necrosis.