Toxic effects of the photoproducts of chlorpromazine on cultured hepatocytes

Authors

  • José V. Castell M.D.,

    Corresponding author
    1. Centro de Investigación, Hospital La Fe, Instituto Nacional de la Salud, 46009 Valencia, Spain and Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, 46010 Valencia, Spain
    • Centro de Investigación, Hospital La Fe, Instituto Nacional de la Salud, 46009 Valencia, Spain
    Search for more papers by this author
  • M. A. José Gómez-Lechón,

    1. Centro de Investigación, Hospital La Fe, Instituto Nacional de la Salud, 46009 Valencia, Spain and Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, 46010 Valencia, Spain
    Search for more papers by this author
  • Miguel A. Miranda,

    1. Centro de Investigación, Hospital La Fe, Instituto Nacional de la Salud, 46009 Valencia, Spain and Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, 46010 Valencia, Spain
    Search for more papers by this author
  • Isabel M. Morera

    1. Centro de Investigación, Hospital La Fe, Instituto Nacional de la Salud, 46009 Valencia, Spain and Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, 46010 Valencia, Spain
    Search for more papers by this author

Abstract

The photodegradation of chlorpromazine, a drug frequently used in psychotherapy, was examined under different sets of experimental conditions. A primary culture of rat hepatocytes was used to evaluate the possible hepatotoxicity of the chlorpromazine photoproducts, keeping in mind the following criteria: leakage of cytosolic enzymes; attachment index to culture plates, and albumin synthesis. Cells exposed to concentrations greater than 10−4M of the photomixtures showed extensive leakage of GOT and GPT into the culture medium and, at the same time, the cell attachment was seriously impaired. A concentration of 10−7M of the photoproducts proved capable of inhibiting the synthesis of albumin (20%). Photoproducts obtained after aerobic irradiations were as toxic for hepatocytes as those found in anaerobic conditions. The implications of our results in connection with the relevance of oxygen-dependent photoreactions of chlorpromazine to its phototoxicity, and the possible appearance of hepatic alterations in patients treated with the drug after exposure to the sunlight, are discussed.

Ancillary