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Ultrastructural changes during cholestasis induced by chlorpromazine in the isolated perfused rat liver

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Virchows Archiv B

Summary

Addition of cholestatic doses of chlorpromazine-HCl to the perfusate of isolated rat livers produces widespread changes in hepatocyte membrane structure. These findings include a marked increase in intrasinusoidal cytoplasmic bullae, appearance of intracellular vacuoles within hepatocytes at both sinusoidal and biliary poles, dilation of bile canaliculi and evagination of canalicular diverticuli, and the formation of myeloid bodies within hepatocytes. These findings obtained in the bile acid depleted perfused liver may result from physicochemical interactions between chlorpromazine or its metabolites and lipid-protein components of cell membranes, consistent with chlorpromazine’s properties as a cationic detergent. They occur independently of the vasoconstrictive effects of chlorpromazine and suggest that chlorpromazine may produce cholestasis by altering hepatocyte membrane function.

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Authors and Affiliations

  1. Liver Study Unit, Department of Medicine and Department of Pathology, University of Chicago, 60637, Chicago, Illinois, USA

    Z. Hruban, N. Tavoloni,  J. S. Reed & J. L. Boyer

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  1. Z. Hruban
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  2. N. Tavoloni
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  3. J. S. Reed
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  4. J. L. Boyer
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Hruban, Z., Tavoloni, N., Reed, J.S. et al. Ultrastructural changes during cholestasis induced by chlorpromazine in the isolated perfused rat liver. Virchows Arch. B Cell Path. 26, 289–305 (1978). https://doi.org/10.1007/BF02889557

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