title: Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats.
abstract: BACKGROUND
  Cyclosporin A (CsA) is one of the most important immunosuppressive agents. However, its clinical use is strongly limited by several side effects including hepatotoxicity which remains a major clinical problem. Involvement of reactive oxygen species (ROS) in CsA-induced hepatotoxicity has been reported.
  
  
  OBJECTIVE
  This study investigates the potential protective role of wheat germ oil (WGO) as an antioxidant against CsA-induced hepatotoxicity.
  
  
  METHODS
  Twenty-four male Wistar albino rats (six animals in each group) received castor oil, the vehicle of CsA i.p. (control) or either CsA (25 mg/kg/d i.p.), WGO (900 mg/kg/d by oral gavage), or CsA in combination with WGO daily for 21 d.
  
  
  RESULTS
  CsA administration significantly increased serum levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, an increase in lipid peroxidation, inducible NO-synthase (iNOS), and NF-κB expression were observed in hepatic tissues of CsA-alone-treated rats. Furthermore, significant reduction in the hepatic content of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) was also observed in CsA-alone-treated animals. Moreover, histopathological changes occurred in CsA-alone-treated rats. Concomitant administration of WGO along with CsA improved all these parameters. Most interestingly, the immunosuppressive effect of CsA was not affected by WGO.
  
  
  CONCLUSIONS
  The present study suggests that concomitant use of WGO might be useful in reducing liver toxicity induced by CsA via inhibition of ROS, iNOS, and NF-κB expression.
authors: Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University , Cairo , Egypt.
authors: El-Sayed
authors: el-S
authors: Akool
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D016572:Cyclosporine; D019610:Cytoprotection; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007376:Interleukin-2 / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010938:Plant Oils / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014908:Triticum / Q000737:chemistry
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D016328:NF-kappa B; D010938:Plant Oils; D017382:Reactive Oxygen Species; C050055:wheat germ oil; D016572:Cyclosporine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: Calcineurin inhibitors; liver toxicity; oxidative damage