An evaluation of the phenomenon of cytoprotection using quantitative histological criteria

Abstract

The concept of ‘cytoprotection’ is derived from observations that exogenous prostaglandins protect the gastric mucosa against injurious agents at doses insufficient to inhibit acid secretion. Measurements of the extent of cytoprotection generally rely on inspection of the open stomach for assessment of the extent of damage. Recent studies indicate that such macroscopic criteria are inaccurate. This study reports the development of quantitative histological techniques that enable valid studies of cytoprotection. Using a rat model of cytoprotection, injury was induced with 1 ml of absolute ethanol. Cytoprotection was induced with 25 μg prostaglandin E 2 (PG) intragastrically 15 or 30 min prior to ethanol exposure. The area of macroscopic damage was measured with a computer‐based digitizer. Semi‐thin plastic sections of eight separate areas of the stomach were examined histologically and the length and depth of damage were measured using the digitizer. Surface area and volume of mucosal damage were calculated from these values. On macroscopic assessment after exposure to ethanol for 15 min, 44.6% of the surface appeared damaged. After pretreatment with PG the extent of ethanol damage appeared to be reduced. On microscopic assessment, however, the extent of damage was much greater with 94.5% of the surface damaged after ethanol alone and 73.7% surface damaged after pretreatment with PG. Thus, macroscopic assessment clearly underestimates the extent of damage. However, these data do indicate that PG protects the surface epithelium from the effects of ethanol. A much clearer demonstration of protection is evident from measurement of the volume of mucosa damaged. After ethanol alone, 31.5% of the mucosal volume was damaged compared with 3.8% when pretreatment by PG was given. When measurements were performed after exposure to ethanol for 30 min, significantly less surface area damage was present in the ethanol group. All other measurements were not different from the 15 min results. This study confirms the existence of cytoprotection, but indicates that macroscopic assessment underestimates the extent of damage, particularly in the cytoprotected stomach. Techniques for accurate microscopic measurement of the extent of damage are described which permit comparison between different cytoprotective agents.