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CYP2E1 potentiates binge-alcohol-induced gut leakiness, steatohepatitis and apoptosis

Thursday, November 07, 2013 — Poster Session II

12:00 p.m. – 2:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • MA Abdelmegeed
  • A Banerjee
  • SH Y
  • SW Jang
  • FJ Gonzalez
  • A Keshavarzian
  • BJ Song


We aimed to investigate the not very well-established role of CYP2E1 in binge alcohol-mediated gut leakiness, oxidative stress, steatohepatitis and apoptosis. Female wild-type (WT) and Cyp2e1-null mice were treated with three doses of oral binge ethanol (WT-EtOH) or dextrose. Intestinal histology of only WT-EtOH exhibited marked ulceration and blebbing of lamina propria while liver histology obtained at 6 h after the last ethanol dose showed that only WT-EtOH mice developed steatosis with scattered inflammatory foci. This was accompanied by increased levels of serum endotoxin, hepatic enterobacteria and triglycerides, all of which were reversed when WT-ETOH mice were treated with chlormethiazole, a specific inhibitor of CYP2E1. WT-EtOH exhibited elevated amounts of serum TNF-α, hepatic cytokines, CYP2E1 and lipid peroxidation with decreased levels of SOD2 and suppressed ALDH2 activity. Hepatocyte apoptosis was increased in only WT-EtOH, as evidenced by TUNEL assay and elevated levels of several pro-apoptotic proteins. Autophagy, involved in lipid homeostasis and preventing apoptosis, was inhibited as revealed by decreased levels of Atg-5, Beclin, Atg-7, and Atg-12. These data indicate that CYP2E1 is critical in the binge alcohol-mediated increased gut leakage, endotoxemia, inflammation, oxidative stress and inhibition of autophagy, contributing to steatohepatitis and apoptosis.

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