Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation

Zhenhua Ren, Fanmuyi Yang, Xin Wang, Yongchao Wang, Mei Xu, Jacqueline A. Frank, Zun ji Ke, Zhuo Zhang, Xianglin Shi, Jia Luo

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 (5 g/kg, 25% ethanol w/v) daily for 3 days. 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 3 days. 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.

Original languageEnglish
Pages (from-to)11-19
Number of pages9
JournalToxicology and Applied Pharmacology
Volume308
DOIs
StatePublished - Oct 1 2016

Bibliographical note

Funding Information:
This research is supported by grants from the National Institutes of Health (NIH) ( AA017226 and AA015407 ). It is also supported in part by the U.S. Department of Veterans Affairs , Veterans Health Administration, Office of Research and Development [Biomedical Laboratory Research and Development: Merit Review ( BX001721 )].

Publisher Copyright:
© 2016 Elsevier Inc.

Keywords

  • Alcohol
  • Apoptosis
  • Drinking pattern
  • Inflammation
  • Insulin
  • Pancreatitis

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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