Effects of fibrates, anti-inflammatory drugs and antidepressants in the fish hepatoma cell line PLHC-1: Cytotoxicity and interactions with cytochrome P450 1A

Effects of 11 pharmaceuticals belonging to three therapeutic classes (lipid regulators from the fibrate group, non-steroidal anti-inflammatory drugs and anti-depressives from the selective serotonin reuptake inhibitors group) were assessed in the fish hepatoma cell line (PLHC-1) by looking at cytotoxicity and interactions with cytochrome P450 1A (CYP1A) function. Among the tested pharmaceuticals, fluoxetine and paroxetine exerted cytotoxic effects, cell viability decreased to 52% and 6% after 24 h of exposure to 20 mu M fluoxetine and paroxetine, respectively. The cytotoxicity of both compounds was modulated by cytochrome P450 inhibitors and was dramatically reduced when culture medium was supplemented with reduced glutathione and vitamin E succinate. Additionally, exposure of PLHC-1 cells to some pharmaceuticals led to an early and transient induction of ethoxyresorufin O-deethylase (EROD) activity: bezafibrate and antidepressants induced EROD activity at a concentration of 1 mu M whereas clofibrate, ibuprofen and naproxen acted as inducers at a higher concentration (10 mu M). These effects might be of toxicological concern since alterations of CYP1A may affect xenobiotic metabolism and toxicity. (C) 2008 Elsevier Ltd. All rights reserved.