title: Evaluation of the protective effect of silibinin against diazinon induced hepatotoxicity and free-radical damage in rat liver.
abstract: BACKGROUND
  Diazinon (0,0-Diethyl 0-(1-6-methyl-2-isoprophyl 4 pyrimidinyl) phosphorothioate) (DI) is a very effective organophosphate pesticide, used widely in agriculture. Consequently, data on poisoning cases secondary to DI exposure are important. The DI may affect a variety of tissues, including liver. Silibinin is a pharmacologically active constitute of Silybum marianum, with documented antioxidant activity.
  
  
  OBJECTIVE
  The aim of our study was to evaluate both histopathologically and biochemically whether silibinin is protective in DI induced liver damage.
  
  
  METHODS
  Thirty two Wistar albino rats were divided into four groups, as follows: 1) control group - oral corn oil was given; 2) DI group - rats were administered orally 335 mg/kg in the corn oil solution; 3) Silibinin group - 100 mg/kg/day silibinin was given alone orally, every 24 hours for 7 days; 4) Silibinin + DI group - DI plus silibinin was given. All rats were sacrificed at the end of experiment. Superoxide dismutases (SOD), glutathione peroxidase (GPX), nitric oxide (NO) and myeloperoxidase (MPO) were investigated in serum and liver tissue. In addition, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activities were evaluated. The liver tissue was evaluated histopathologically with Hematoxilin & Eosin dye.
  
  
  RESULTS
  Biochemically, ALT, AST, NO, MPO in serum and NO, MPO in liver tissue were found to be significantly higher in DI group, compared to control group (P < 0.001). In Group Silibinin + DI, serum AST, ALT, NO, MPO levels were significantly lower (P < 0.01), and both serum and tissue SOD activities were significantly higher, compared to DI group (P < 0.001). Diazinon induced histopathological changes in liver tissue were: severe sinusoidal dilatation, moderate disruption of the radial alignment of hepatocytes around the central vein, severe vacuolization in the hepatocyte cytoplasm, inflammation around central vein and portal region. In rats receiving both DI and silibinin, the DI induced changes accounted for less sinusoidal dilatation, vacuolization in the hepatocyte cytoplasm and the inflammation around central vein and portal region (P < 0.05).
  
  
  CONCLUSIONS
  The DI was found to induce liver damage by oxidative stress mechanisms. Silibinin reduced the oxidative stress by inducing antioxidant mechanisms, thereby showing protective effect against DI induced liver damage. Further studies with silibinin should be performed regarding DI toxicity.
authors.affiliation: Department of Emergency Medicine, School of Medicine, Mugla Sitki Kocman University, Mugla, Turkey.
authors.forename: Halil
authors.initials: H
authors.lastname: Beydilli
authors.affiliation: Department of Medical Biochemistry, School of Medicine, Mugla Sitki Kocman University, Mugla, Turkey.
authors.forename: Nigar
authors.initials: N
authors.lastname: Yilmaz
authors.affiliation: Department of Medical Biology, School of Medicine, Mugla Sitki Kocman University, Mugla, Turkey.
authors.forename: Esin Sakalli
authors.initials: ES
authors.lastname: Cetin
authors.affiliation: Department of Pediatrics, School of Medicine, Mugla Sitki Kocman University, Mugla, Turkey.
authors.forename: Yasar
authors.initials: Y
authors.lastname: Topal
authors.affiliation: Department of Medical Pathology, School of Medicine, Mugla Sitki Kocman University, Mugla, Turkey.
authors.forename: Ozgur Ilhan
authors.initials: OI
authors.lastname: Celik
authors.affiliation: Department of Internal Medicine, School of Medicine, Mugla Sitki Kocman University, Mugla, Turkey.
authors.forename: Cem
authors.initials: C
authors.lastname: Sahin
authors.affiliation: Department of Medical Biology, School of Medicine, Mugla Sitki Kocman University, Mugla, Turkey.
authors.forename: Hatice
authors.initials: H
authors.lastname: Topal
authors.affiliation: Department of Biology, School of Science, Afyon Kocatepe University, Afyon, Turkey.
authors.forename: Ibrahim Hakki
authors.initials: IH
authors.lastname: Cigerci
authors.affiliation: Department of Infectious Diseases, School of Medicine, Mugla Sitki Kocman University, Mugla, Turkey.
authors.forename: Hamdi
authors.initials: H
authors.lastname: Sozen
keywords: Antioxidants; Diazinon; Histopathology; Liver; Oxidative Stress