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 microM 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 microM whereas clofibrate, ibuprofen and naproxen acted as inducers at a higher concentration (10 microM). These effects might be of toxicological concern since alterations of CYP1A may affect xenobiotic metabolism and toxicity.
Thibaut
Rémi
R
Environmental Chemistry Department, IIQAB-CSIC, C/Jordi Girona, 18, 08034 Barcelona, Spain. rthqam@cid.csic.es
Porte
Cinta
C
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000633:toxicity*; D000928:Antidepressive Agents / Q000378:metabolism / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002995:Clofibric Acid / Q000378:metabolism / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D023781:Fundulidae; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015262:Xenobiotics / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D014874:Water Pollutants, Chemical; D015262:Xenobiotics; D002995:Clofibric Acid; D019363:Cytochrome P-450 CYP1A1