title: Nicotine enhances ethanol-induced fat accumulation and collagen deposition but not inflammation in mouse liver.
abstract: BACKGROUND
  Alcohol and tobacco are frequently co-abused. Tobacco smoke increases alcoholic steatosis in apoE(-/-) mice. Tobacco smoke contains more than 4000 chemicals, but it is unknown which compounds in tobacco smoke play a major role in increasing alcoholic steatosis.
  
  
  METHODS
  C57BL/J6 mice were intraperitoneally injected with nicotine at 1 mg/kg every day or saline at the same volume as a control and the mice were fed dextrose-control or ethanol Lieber-DeCarli liquid diets. Three weeks later the mice were sacrificed after overnight fasting.
  
  
  RESULTS
  Neither nicotine injection nor ethanol feeding alone increased serum levels of triglyceride, but the combination of nicotine and ethanol increased serum levels of triglyceride. Both nicotine injection alone and ethanol feeding alone increased hepatic collagen type I deposition, and nicotine injection and ethanol feeding combined further increased hepatic collagen type I deposition. The combination of nicotine and ethanol also activated hepatic stellate cells, a principal liver fibrogenic cell. Hepatic fat accumulation was induced by ethanol feeding, which was further enhanced by nicotine injection. Ethanol feeding caused an increase in serum ALT, but nicotine did not further increase serum ALT levels. Lipid droplets and inflammatory foci were observed in liver sections from ethanol-fed mice; nicotine treatment increased the number and size of lipid droplets, but not the number and size of inflammatory foci. Nicotine did not further increase ethanol-induced hepatic neutrophil infiltration.
  
  
  CONCLUSIONS
  These results suggest that nicotine enhances ethanol-induced steatosis and collagen deposition, but nicotine has no effect on ethanol-induced inflammation.
authors.affiliation: Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. yongke.lu@mssm.edu
authors.forename: Yongke
authors.initials: Y
authors.lastname: Lu
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Ward
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Cederbaum
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D065637:Cytochrome P-450 CYP2A6; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D005234:Fatty Liver / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D055166:Hepatic Stellate Cells / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D024042:Collagen Type I; D014280:Triglycerides; D000431:Ethanol; D009538:Nicotine; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D000410:Alanine Transaminase