Promethazine inhibited CCl4 stimulated microsomal lipid peroxidation in vitro at concentrations ranging from 10(-3) to 10(-8)M. CCl4 administered to rats at a dose of 1 ml/kg decreased the arachidonic acid content of microsomal lipids after 6 hours of intoxication. Prior promethazine treatment, at dosage regimes that preclude CCl4 induced liver necrosis at 24 hours, did not significantly prevent the CCl4 induced decrease in arachidonic acid content. Moreover, promethazine itself produced a similar decrease but in complete absence of liver damage. Results suggest that either lipid peroxidation is not relevant to liver injury or that the arachidonic acid decrease in microsomal lipids is not evidence for lipid peroxidation occurrence or that promethazine effects are not related to inhibition of lipid peroxidation.
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