title: The effects of di(2-ethylhexyl)phthalate on rat liver in relation to selenium status.
abstract: This study was performed to determine the hepatotoxicity of di(2-ethylhexyl)phthalate (DEHP) in relation to selenium status. In 3-week-old Sprague-Dawley rats, selenium deficiency was induced by a ≤0.05 selenium mg/kg. A selenium supplementation group was given 1 mg selenium/kg diet for 5 weeks. Di(2-ethylhexyl)phthalate-treated groups received 1000 mg/kg dose by gavage during the last 10 days of the experiment. Histopathology, peroxisome proliferation, catalase (CAT) immunoreactivity and activity and apoptosis were assessed. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR1)], superoxide dismutase (SOD), and glutathione S-transferase (GST); aminotransferase, total glutathione (tGSH), and lipid peroxidation (LP) levels were measured. Di(2-ethylhexyl)phthalate caused cellular disorganization while necrosis and inflammatory cell infiltration were observed in Se-deficient DEHP group (DEHP/SeD). Catalase activity and immunoreactivity were increased in all DEHP-treated groups. Glutathione peroxidase 1 and GPx4 activities decreased significantly in DEHP and DEHP/SeD groups, while GST activities decreased in all DEHP-exposed groups. Thioredoxin reductase activity increased in DEHP and DEHP/SeS, while total SOD activities increased in all DEHP-treated groups. Lipid peroxidation levels increased significantly in SeD (26%), DEHP (38%) and DEHP/SeD (71%) groups. Selenium supplementation partially ameliorated DEHP-induced hepatotoxicity; while in DEHP/SeD group, drastic changes in hepatic histopathology and oxidative stress parameters were observed.
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
authors.forename: Pınar
authors.initials: P
authors.lastname: Erkekoglu
authors.forename: Naciye D
authors.initials: ND
authors.lastname: Zeybek
authors.forename: Belma K
authors.initials: BK
authors.lastname: Giray
authors.forename: Walid
authors.initials: W
authors.lastname: Rachidi
authors.forename: Murat
authors.initials: M
authors.lastname: Kızılgün
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hininger-Favier
authors.forename: Alain
authors.initials: A
authors.lastname: Favier
authors.forename: Esin
authors.initials: E
authors.lastname: Asan
authors.forename: Filiz
authors.initials: F
authors.lastname: Hincal
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects; D020675:Peroxisomes / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000172:deficiency* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D004051:Diethylhexyl Phthalate; D002374:Catalase; D012643:Selenium
keywords: antioxidant enzymes; di(ethylhexyl)phthalate; liver; oxidative stress; selenium deficiency; selenium supplementation