Mild irritants prevent gastric necrosis through "adaptive cytoprotection" mediated by prostaglandins

Abstract

Several prostaglandins (PG) were found earlier to be cytoprotective for the stomach and the intestine. We now report that mild irritants, given intragastrically, are also cytoprotective by stimulating the release of PG by the stomach. Several "mild irritants," 10-20% ethanol, 0.2-0.35 M HCl, 0.05-0.075 M NaOH, 2-4% NaCl, and water at 70 degrees C, were given orally to fasted rats. Fifteen minutes later, one of the following necrotizing agents was administered orally: 100% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl solution, and boiling water. One hour later, the stomachs were removed and necrotic lesions graded. The mild irritants inhibited the necrotic lesions dose dependently. After a single treatment, protection lasted 1 h; repeated administrations maintained cytoprotection for as long as the mild irritants were being given. Indomethacin, an inhibitor of PG synthesis, abolished cytoprotection by mild irritants. After oral administration of NaOH at cytoprotective concentrations (0.01-0.1 M), the amounts of PGE2, PGF2 alpha, and thromboxane B2 formed by the gastric mucosa increased steadily up to threefold. The protection elicited by mild irritants is called "adaptive cytoprotection." The increased synthesis of PG may represent a physiological, natural defense mechanism that may be necessary to maintain cellular integrity of the gastrointestinal mucosa, in spite of the hostile environment caused by luminal contents.

Gastroprotective Activity of FRG-8813, a Novel Histamine H2-Receptor Antagonist, in Rats

“…First, since both oral and i.p. treatments with FRG-8813 were effective, the protective effect is not the result of "adaptive cytoprotection", which occurs following the application of a mild irritant to the gastric mucosa and which may be mediated by increased levels of tissue prostaglandin (23,24). Our studies also showed that pretreatment with indomethacin (10 mg/kg, s.c.) did not affect the gastroprotection of FRG-8813, indicating that the presence of endogenous prostaglandins is not essential to the protective activity by FRG-8813.…”

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium graveolens) in rats

“…The following necrotizing agents were administered orally in a volume of 1 mL: 80% ethanol, 0.2 M NaOH and 25% NaCl (Robert et al, 1983). The celery extract in doses of (250 and 500 mg/kg body weight) was administered orally 30 min before the necrotizing agents treatment.…”

Facilitation by Endogenous Prostaglandins of Capsaicin-Induced Gastric Protection in Rodents through EP2 and IP Receptors

“…Gastric mucosal integrity is maintained by multiple factors both paracrine and neuronal (Robert et al, 1979(Robert et al, , 1983Holzer and Sametz, 1986;Whittle et al, 1990;Holzer, 1998). The former includes prostaglandins (PGs) (Robert et al, 1979(Robert et al, , 1983Miller, 1983) and nitric oxide (Whittle et al, 1990), whereas capsaicin-sensitive afferent neurons play a central role in the neuronal protection of the stomach (Holzer, 1998).…”

“…The former includes prostaglandins (PGs) (Robert et al, 1979(Robert et al, , 1983Miller, 1983) and nitric oxide (Whittle et al, 1990), whereas capsaicin-sensitive afferent neurons play a central role in the neuronal protection of the stomach (Holzer, 1998). Studies have demonstrated that capsaicin, a selective stimulator of these afferent neurons, protects the gastric mucosa against various ulcerogenic stimuli such as necrotizing agents (Holzer and Sametz, 1986).…”