title: Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice.
abstract: Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl₄-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl₄ exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl₄ and euthanized 24-96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl₄-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl₄ exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl₄-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl₄. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. kdeshpande@outlook.com.|Department of Pathology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. kdeshpande@outlook.com.
authors.forename: Krutika T
authors.initials: KT
authors.lastname: Deshpande
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. jawahal@hotmail.com.|Department of Pathology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. jawahal@hotmail.com.
authors.forename: Shinlan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. jmccracken2@kumc.edu.|Department of Pathology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. jmccracken2@kumc.edu.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: McCracken
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. ljiang@kumc.edu.|Department of Pathology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. ljiang@kumc.edu.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. tagaw75@gmail.com.|Department of Pathology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. tagaw75@gmail.com.
authors.forename: Ta Ehpaw
authors.initials: TE
authors.lastname: Gaw
authors.affiliation: Department of Gastroenterology and Hepatology, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA. lxk176@case.edu.
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Kaydo
authors.affiliation: Department of Gastroenterology and Hepatology, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA. zrichar1@nd.edu.
authors.forename: Zachary C
authors.initials: ZC
authors.lastname: Richard
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. moneil@kumc.edu.|Department of Pathology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. moneil@kumc.edu.
authors.forename: Maura F
authors.initials: MF
authors.lastname: O'Neil
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. mpritchard@kumc.edu.|Department of Pathology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. mpritchard@kumc.edu.
authors.forename: Michele T
authors.initials: MT
authors.lastname: Pritchard
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000431:Ethanol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D002251:Carbon Tetrachloride
keywords: carbon tetrachloride; ethanol; fibrosis; inflammation; liver regeneration; matrix remodeling; wound healing