Toxic effects of the photoproducts of chlorpromazine on cultured hepatocytes.

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(-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.