Low dose ethanol potentiates indomethacin induced inhibition of wound re-epithelialization in duodenal monolayers.
Nonsteroidal anti-inflammatory drugs (NSAIDs) induce gastroduodenal mucosal injury and ulceration, and delay ulcer healing. In contrast, the effects of low dose ethanol in induction of gastroduodenal mucosal injury, and the subsequent wound repair remains unclear. The aim of this study was to determine, using an in-vitro duodenal epithelial wound model, whether low clinically relevant doses of ethanol or indomethacin interfere with the wound re-epithelialization of duodenal epithelial monolayers. The possible potentiating effect of ethanol on indomethacin modulation of duodenal re-epithelialization was also examined. In-vitro epithelial wounds were created in confluent IEC-6 duodenal epithelial monolayers by a razor blade scrape. Ethanol at low concentrations (0.25, 0.5, 0.75%) did not have significant effect on duodenal wound re-epithelialization. Similarly, low doses of indomethacin (.01,.05, 0.1 mM) also did not have a significant effect on wound re-epithelialization. However, the combination of ethanol (0.5 or 0.75%) and indomethacin (0.1mM) produced a marked inhibition of IEC-6 re-epithelialization. At the low doses used, ethanol and indomethacin (individually or in combination) did not have direct cytotoxic effect on IEC-6 cells. Ethanol or indomethacin (at the studied concentrations) had only minimal effect on the actin stress fibers in the cells at the migration front. However, in combination, they almost completely abolished the actin stress fibers at the migration front. These findings demonstrate that while low clinically relevant doses of ethanol and indomethacin individually do not affect re-epithelialization of wounded duodenal epithelial monolayers, in combination they produce a significant inhibition.
Mohajer
Babak
B
DVA Medical Center, Gastroenterology Section, 5901 E. Seventh Street, Long Beach, CA 90822, USA.
Tarnawski
Andrzej
A
Hoa
Neil T
NT
Tran
Daniel
D
Chen
Joseph
J
Park
Harry
H
Ma
Thomas Y
TY
D008841:Actin Cytoskeleton / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004386:Duodenum / Q000166:cytology / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D007213:Indomethacin / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000431:Ethanol; D007213:Indomethacin