Levamisole represents one of several new compounds that exhibit immunomodulating activity. Pharmacological data have documented a relationship between liver drug metabolism of levamisole and its subsequent immunomodulating activity. To directly investigate this relationship in a controlled manner, primary cultures of adult rat hepatocytes were treated with levamisole, and ultrastructural and biochemical effects were analyzed. Ultrastructurally, levamisole did not disrupt the cellular architecture of the hepatocytes. Biochemically, levamisole stimulated alkaline phosphatase activity and elevated microsomal cytochrome P-450 content after a 48-hr incubation. High pressure liquid Chromatographie analysis of levamisole metabolites produced by cultured hepatocytes suggested the formation of a hepatocyte-specific metabolite(s) that may be associated with its immunological mode of action.
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