title: Effect of iprodione, a dicarboximide fungicide, on primary cultured rainbow trout (Oncorhynchus mykiss) hepatocytes.
abstract: As is known from literature, iprodione, a dicarboximide fungicide, has a highly specific action, with a capacity to cause oxidative damage through production of free oxygen radicals (ROS), but it does not appear to be species selective. Since this substance is able to diffuse in water, evaluation of its capacity to induce oxidative damage in an aquatic organism such as the rainbow trout (Oncorhynchus mykiss) was considered of particular interest. A study was, therefore, undertaken to investigate the effect of iprodione on free radicals (ROS) and malondialdehyde (MDA) production, reduced glutathione (GSH) content and catalase activity (CAT), in primary cultured trout hepatocytes, following treatment with 0.2, 0.3 and 0.4 mM concentrations for a 24-h period. The iprodione 0.3 and 0.4 mM concentrations increased both ROS and MDA production and decreased GSH content and CAT activity. These results suggest that iprodione is able to produce oxidative damage in primary cultured fish hepatocytes, thus confirming that its action is specific, but not species selective. It is also well known that ROS production in fungi is due to interaction with the flavin enzyme NADPH cytochrome c reductase to the extent that the normal electron flow from NADPH to cytochrome c is blocked. In contrast, we observed that, in primary cultured trout hepatocytes, iprodione appears to have no effect on NADPH cytochrome c reductase activity. It is, therefore, possible to presume that the mechanism of oxidative damage in trout hepatocytes differs from that observed in fungi. Moreover, our experiments also demonstrate that iprodione is able to induce "in vitro" CYP1A1, leading to the conclusion that the production of ROS is due to this phenomenon.
authors.affiliation: Department of Pharmacology, Chemotherapy and Medical Toxicology E. Trabucchi, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy. sonia.radice@unimi.it
authors.forename: S
authors.initials: S
authors.lastname: Radice
authors.forename: M
authors.initials: M
authors.lastname: Ferraris
authors.forename: L
authors.initials: L
authors.lastname: Marabini
authors.forename: S
authors.initials: S
authors.lastname: Grande
authors.forename: E
authors.initials: E
authors.lastname: Chiesara
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000633:toxicity*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005659:Fungicides, Industrial / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006827:Hydantoins; D015227:Lipid Peroxidation / Q000187:drug effects; D017686:Oncorhynchus mykiss; D017382:Reactive Oxygen Species
chemical_list: D005659:Fungicides, Industrial; D006827:Hydantoins; D017382:Reactive Oxygen Species; D000620:Aminoimidazole Carboxamide; D002374:Catalase; D019363:Cytochrome P-450 CYP1A1; D005978:Glutathione; C033148:iprodione