The additive effect of ethanol and extract of cigarette smoke on rabbit esophagus epithelium

The combination of alcohol and smoking takes a place in the epidemiology and pathogenesis of gastroesophageal reflux disease and squamous cancers of the esophagus. Therefore, a study was designed to assess the impact of these agents alone or in combination on the structure and function of squamous epithelium of rabbit esophagus. Rabbit esophageal epithelium was mounted in Ussing Chambers, exposed luminally for ethanol (1-10%), extract of cigarette smoke (EOCS) and combinations or sequential application of these agents. An in-vivo model was also used to mimic conditions more representative of human alcohol consumption. Ethanol (1-10%) dose dependently decreased tissue resistance. Extract of cigarette smoke caused a reduction on transepithelial potential difference (PD), short circuit current. Combinations of EOCS, ethanol (5-10% EtOH and EOCS 1-2) showed a more pronounced decrease than agents alone, mainly the result of EOCS. In vivo studies showed that EOCS administration dropped PD dose dependently. In-vivo 10% EtOH, EOCS-2 dropped PD (55%) similar to in-vitro 5% EtOH, EOCS-1. The effect was clearly additive; boluses of 10% ethanol (36%) and EOCS-2 (17%) decreased PD and combination of agents resulted in a 55% drop on PD which is a very similar decrease compared to the sum of the separate effects of agents (53%). Ethanol affected the barrier and cigarette smoke altered ion transport on rabbit esophageal epithelium under conditions reflecting human consumption. Results were consistent with in vivo and in vitro conditions except higher concentrations were needed in vivo. When applied, these agents showed an additive effect. Ethanol predisposed the tissue to the effect of EOCS.