title: Nonylphenol induces liver toxicity and oxidative stress in rat.
abstract: Nonylphenol (NP) is one of the most widely used synthetic xenoestrogens in detergents, plastic products, paints and the most important environmental degradation factor. In this study, the effects NP was investigated on hepatic oxidative stress-related gene expression in rats.
  
  
  
  Wistar male rats weighing 150-200 g were divided into control and NP receiving groups. NP was given in three doses (5, 25, and 125 μg/kg). All doses were given by gavage and the experiment continued for a consecutive 35 days. AST, ALT and ALP determined by the colorimetric method. The RNA was extracted from the rats liver tissue and RT- PCR was used to investigate the changes in gene expression. For this purpose, primers and specific probes of HO1 and Gadd45b genes as well as B-actin as control were prepared and the expression of each gene was separately assessed with ABI-7300. Hematoxylin and eosin staining was performed for evaluating of cell death.
  
  
  
  The data from our study indicated nonylphenol increased alkaline phosphatase level but not changed aspartate aminotransferase and alanine aminotransferase in serum. That various doses of NP result in a dose-dependent increase in the expression of HO-1 gene. The intensified expression of HO-1 was statistically significant just at the doses of 25 and 125 μg/kg compared to control group (p < 0.05). In addition, it was shown that different doses of nonylphenol raised the expression of Gadd45b gene and this increase was significantly evident at 5 μg/kg (p < 0.05). Histological evaluation also indicated that NP increased hepatocytes cell death.
  
  
  
  We conclude that NP increased serum alkaline phosphatase, lead to liver damage and can increase the expression of HO1 and Gadd45b genes and may modify the toxic effects on liver through induction of oxidative stress.
authors: Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
authors: Sohrab
authors: S
authors: Kazemi
authors: Cellular and Molecular Biology Research Center, Health Research Center, Babol University of Medical Sciences, Babol, Iran.
authors: Seydeh Narges
authors: SN
authors: Mousavi Kani
authors: Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
authors: Maryam
authors: M
authors: Ghasemi-Kasman
authors: Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
authors: Fahimeh
authors: F
authors: Aghapour
authors: Cellular and Molecular Biology Research Center, Health Research Center, Babol University of Medical Sciences, Babol, Iran.
authors: Hamidreza
authors: H
authors: Khorasani
authors: Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran. Electronic address: moghadamnia@yahoo.com.
authors: Ali Akbar
authors: AA
authors: Moghadamnia
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000633:toxicity*; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097642:GADD45 Proteins
chemical_list: D000469:Alkaline Phosphatase; D000943:Antigens, Differentiation; D051547:Heme Oxygenase-1; D010636:Phenols; C508094:Gadd45b protein, rat; D000097642:GADD45 Proteins; C025256:nonylphenol
keywords: Gadd45b; HO1; Hepatotoxicity; Liver damage; Nonylphenol; Oxidative stress