title: Effects of antioxidant agents against cyclosporine-induced hepatotoxicity.
abstract: BACKGROUND
  To investigate the potential protective antioxidant role of ursodeoxycholic acid (UDCA), melatonin, and allopurinol treatment in cyclosporine (CsA)-induced hepatotoxicity.
  
  
  METHODS
  Hepatotoxicity was established in Sprague-Dawley rats by daily administration of CsA. Treatment groups were additionally administered UDCA, melatonin, or allopurinol treatments. Rats that received no CsA and no treatments served as a control group. Liver samples from each group were examined by histopathologic analysis to determine the effects of CsA treatment on liver morphology. Biochemical assays were also used to determine the effect of CsA treatment on liver function, in the presence or absence of UDCA, melatonin, or allopurinol.
  
  
  RESULTS
  CsA treatment induced hepatotoxicity, resulting in sinusoidal dilatation, congestion, infiltration, hydropic degeneration, and loss of glycogen storage in the liver. From a molecular perspective, the CsA treatment increased levels of malondialdehyde (MDA) levels, decreased levels of reduced glutathione and xanthine oxidase, and decreased activities of superoxide dismutase and catalase. The CsA treatment also resulted in decreased serum total antioxidant capacity, whereas alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin levels, and total oxidant status were increased. Treatment with UDCA, melatonin, or allopurinol reduced the CsA-induced histopathologic changes, as compared with CsA-treated samples. In addition, UDCA, melatonin, or allopurinol treatment mitigated the CsA-induced effects on glutathione and MDA levels, and on superoxide dismutase and catalase activities, as well as reduced the CsA-mediated perturbations in serum levels of total antioxidant capacity, total oxidant status, and alkaline phosphatase.
  
  
  CONCLUSIONS
  UDCA, allopurinol, and melatonin may each help to protect against CsA-induced damage to liver tissues, possibly through effects on the antioxidant system.
authors.affiliation: Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey. Electronic address: akbulutsami@gmail.com.
authors.forename: Sami
authors.initials: S
authors.lastname: Akbulut
authors.affiliation: Department of Histology and Embryology, Inonu University Faculty of Medicine, Malatya, Turkey.
authors.forename: Hulya
authors.initials: H
authors.lastname: Elbe
authors.affiliation: Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey.
authors.forename: Cengiz
authors.initials: C
authors.lastname: Eris
authors.affiliation: Department of Anatomy, Adiyaman University Faculty of Medicine, Adiyaman, Turkey.
authors.forename: Zumrut
authors.initials: Z
authors.lastname: Dogan
authors.affiliation: Department of Biochemistry, Dicle University Faculty of Medicine, Diyarbakir, Turkey.
authors.forename: Gulten
authors.initials: G
authors.lastname: Toprak
authors.affiliation: Department of Biochemistry, Dicle University Faculty of Medicine, Diyarbakir, Turkey.
authors.forename: Erhan
authors.initials: E
authors.lastname: Yalcin
authors.affiliation: Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey.
authors.forename: Emrah
authors.initials: E
authors.lastname: Otan
authors.affiliation: Department of Biochemistry, Inonu University Faculty of Medicine, Malatya, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Turkoz
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000097:blood; D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016572:Cyclosporine / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D000493:Allopurinol; D014580:Ursodeoxycholic Acid; D016572:Cyclosporine; D014969:Xanthine Oxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D008550:Melatonin; D001663:Bilirubin
keywords: Allopurinol; Antioxidant agents; Cyclosporine; Hepatotoxicity; Melatonin; Ursodeoxycholic acid