title: Absence of cytochrome P450 2A5 enhances alcohol-induced liver injury in mice.
abstract: BACKGROUND
  Ethanol can induce cytochrome P450 2E1, an active generator of reactive oxygen species, and this cytochrome is considered a risk factor for oxidative liver injury. Recently, we found that in addition to P450 2E1 also cytochrome P450 2A5, another isoform of cytochrome P450, can be induced by ethanol, and that ethanol induction of cytochrome P450 2A5 is P450 2E1-dependent.
  
  
  OBJECTIVE
  To investigate the role of cytochrome P450 2A5 in alcohol-induced liver injury.
  
  
  METHODS
  Cytochrome P450 2A5-knockout mice and wild type mice were fed the Lieber-Decarli ethanol liquid diet to induce liver injury. Controls were fed the Lieber-Decarli control diet.
  
  
  RESULTS
  After 4 weeks of feeding with Lieber-Decarli diet, ethanol-induced liver injury was enhanced in the knockout mice compared with wild type mice, as indicated by serum transaminases, hepatic fat accumulation (steatosis), and necroinflammation observed in liver sections with Haematoxylin & Eosin staining. Ethanol-induced oxidative stress was also higher in the knockout mice than the wild types. Ethanol feeding induced cytochrome P450 2A5 in wild type mice but not in the knockout mice, while induction of cytochrome P450 2E1 was comparable in the knockout and wild type mice.
  
  
  CONCLUSIONS
  These results suggest that cytochrome P450 2A5 protects against ethanol-induced oxidative liver injury.
authors: Institute of Liver Diseases, Affiliated Hospital of Jining Medical University, Jining, China.
authors: Feng
authors: F
authors: Hong
authors: Department of Hepatobiliary and Pancreatic Surgery, The First Bethune Hospital, Jilin University, Jilin, China.
authors: Xiyu
authors: X
authors: Liu
authors: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors: Stephen S
authors: SS
authors: Ward
authors: Division of Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors: Huabao
authors: H
authors: Xiong
authors: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors: Arthur I
authors: AI
authors: Cederbaum
authors: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: luyongke@yahoo.com.
authors: Yongke
authors: Y
authors: Lu
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000172:deficiency / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D008108:Liver Diseases, Alcoholic / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress
chemical_list: D015415:Biomarkers; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C585520:Cyp2a5 protein, mouse; D000072467:Cytochrome P450 Family 2
keywords: Cytochrome P450 2A5; Cytochrome P450 2E1; Ethanol; Liver; Oxidative stress