Toxic Effects of the Photoproducts of Chlorpromazine on Cultured Hepatocytes

[EN] 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¿4 M 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¿7 M 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.