title: Paraoxonase 1 and oxidative stress in paediatric non-alcoholic steatohepatitis.
abstract: OBJECTIVE
  Non-alcoholic steatohepatitis (NASH) in children is a significant public health concern. Oxidative stress is an important component in the pathophysiology of NASH. Several enzymatic antioxidant mechanisms protect the liver from oxidative injury. Examination of the expression of these enzymes in NASH livers may provide insight on the roles for these antioxidant mechanisms in the pathophysiology of NASH.
  
  
  METHODS
  The mRNA expression of catalase, glutathione peroxidase 1 (GPX1), glutathione reductase (GSR), paraoxonase 1 (PON1) and other reactive oxygen species-related genes was evaluated by microarray and quantitative real-time PCR analyses. The PON1 protein levels were evaluated in liver and serum by Western blot analyses. Serum enzymatic activities of GPX, GSR and PON1 (paraoxonase and arylesterase activities) were examined.
  
  
  RESULTS
  NASH livers exhibited elevated mRNA expression of catalase and PON1, but not GPX1 or GSR. No difference in serum GPX or GSR activity was detected between NASH patients and controls. Elevated expression of PON1 mRNA and protein was detected in NASH livers, but serum PON1 protein and activities were not elevated.
  
  
  CONCLUSIONS
  Elevated expression of catalase and PON1 suggests protective roles for these antioxidants in NASH livers. Given the importance of oxidative stress in the pathophysiology of NASH, future studies focusing on these enzymes could identify important targets for therapeutic or preventive interventions for NASH patients.
authors.affiliation: Women and Children's Hospital of Buffalo, Department of Pediatrics, the State University of New York, Buffalo, NY, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Desai
authors.forename: Susan S
authors.initials: SS
authors.lastname: Baker
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.forename: Diana A
authors.initials: DA
authors.lastname: Moya
authors.forename: Richard W
authors.initials: RW
authors.lastname: Browne
authors.forename: Lucy
authors.initials: L
authors.lastname: Mastrandrea
authors.forename: Robert D
authors.initials: RD
authors.lastname: Baker
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000367:Age Factors; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002374:Catalase / Q000097:blood / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005979:Glutathione Peroxidase / Q000097:blood / Q000235:genetics; D005980:Glutathione Reductase / Q000097:blood / Q000235:genetics; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D055815:Young Adult; D000094765:Glutathione Peroxidase GPX1
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D002374:Catalase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
keywords: Antioxidant; NAFLD; ROS; catalase; glutathione peroxidase