Prostaglandin prevents alterations in DNA, RNA, and protein in damaged gastric mucosa

Abstract

Fasted rats were given either 16,16-dimethyl-PGE₂ (dmPGE₂) (1 μg/kg) or normal saline subcutaneously followed by the oral administration of 1 ml of 100% ethanol or saline 30 min later. At 1, 3, 6, and 24 hr later, animals were sacrificed, their stomachs examined for necrotic ulcerations, and the incorporation of [³H] thymidine into DNA as well as tissue levels of DNA, RNA, and protein content of glandular mucosa determined. Compared with control animals, severe ulcerations of 70–80% of the glandular mucosa were observed in rats give 100% ethanol at all time periods. Accompanying these ulcerations were marked depressions in tissue levels of DNA and RNA at 1, 3, 6, and 24 hr after exposure to ethanol, and protein at 1, 3, and 6 hr following ethanol. In rats pretreated with dmPGE₂ before ethanol administration, these alterations in tissue levels of DNA, RNA, and protein were prevented as were ulcerations of the glandular stomach at each time period. Synthesis of mucosal DNA was not significantly different from control rats in any of the groups studied. It is concluded that (1) gastric mucosal damage by alcohol is associated with a decrease in tissue levels of DNA, RNA, and protein; (2) dmPGE₂ maintains normal tissue levels of DNA, RNA, and protein by preventing the shedding of mucosal cells by alcohol; and (3) the ability of dmPGE₂ to prevent gastric damage by alcohol is not mediated through stimulation of DNA synthesis.