title: Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation.
abstract: Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5g/kg, 25% ethanol w/v) daily for 3days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas.
authors.affiliation: Department of Anatomy, School of Basic Medicine, Anhui Medical University, Hefei, Anhui, China 230032; Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
authors.forename: Fanmuyi
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
authors.forename: Mei
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Frank
authors.affiliation: Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Zun-Ji
authors.initials: ZJ
authors.lastname: Ke
authors.affiliation: Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, United States.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, United States. Electronic address: jialuo888@uky.edu.
authors.forename: Jia
authors.initials: J
authors.lastname: Luo
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D007249:Inflammation / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects*
chemical_list: D000431:Ethanol
keywords: Alcohol; Apoptosis; Drinking pattern; Inflammation; Insulin; Pancreatitis