The effects of di(2-ethylhexyl)phthalate on rat liver in relation to selenium status

Int J Exp Pathol. 2014 Feb;95(1):64-77. doi: 10.1111/iep.12059. Epub 2013 Nov 4.

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.

Keywords: antioxidant enzymes; di(ethylhexyl)phthalate; liver; oxidative stress; selenium deficiency; selenium supplementation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Catalase / drug effects
  • Catalase / metabolism
  • Diethylhexyl Phthalate / pharmacology*
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Models, Animal
  • Oxidative Stress / drug effects
  • Peroxisomes / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Selenium / deficiency*
  • Selenium / metabolism*
  • Selenium / pharmacology

Substances

  • Diethylhexyl Phthalate
  • Catalase
  • Selenium