Ability of prostaglandin to reduce ethanol injury to dispersed chief cells from guinea pig stomach

Abstract

To determine whether prostaglandin exerts a direct action on individual gastric epithelial cells that protects them from ethanol-induced injury, dispersed chief cells from guinea pig stomach were pretreated with 16,16-dimethyl-prostaglandin E2 (dmPGE2) or placebo before incubation with ethanol or control. Cell injury was assessed in terms of exclusion of Fast Green dye, release of lactate dehydrogenase, alterations of ultrastructure, and pepsinogen secretion stimulated by a variety of secretagogues. Of chief cells 60 +/- 2% were stained by Fast Green if incubated with 10% ethanol for 1 h after pretreatment with placebo, whereas only 38 +/- 1% of cells showed Fast Green staining when pretreated with 2.6 microM dmPGE2 before ethanol exposure. Similarly, 63 +/- 2% of cellular lactate dehydrogenase was released from chief cells pretreated with placebo compared with 36 +/- 4% of lactate dehydrogenase released from cells pretreated with 2.6 microM dmPGE2 (P less than 0.01). The prostaglandin's protective effect persisted throughout a 6-h incubation with ethanol. Scanning and transmission electron micrographs demonstrated disintegration of chief cells pretreated with placebo before ethanol exposure, whereas ultrastructural architecture was relatively preserved among chief cells pretreated with dmPGE2. Preincubation with 8 or 10% ethanol inhibited the subsequent stimulation of pepsinogen secretion caused by carbachol, cholecystokinin, A23187, 12-O-tetradecanoylphorbol 13-acetate, forskolin, or 8-bromoadenosine 3',5'-cyclic monophosphate. Pretreatment with dmPGE2 did not reduce the ethanol-induced inhibition of secretion stimulated by any of these secretagogues. These data indicate that dmPGE2 significantly reduces ethanol-induced damage to dispersed chief cells in terms of alterations of membrane permeability and ultrastructure but does not prevent the ethanol-induced impairment of pepsinogen secretion. These findings provide evidence that dmPGE2 exerts a direct but limited protective action on the gastric chief cell, independent of vascular, paracrine, or neural actions.

Irritant-induced cyclooxygenase-2 is involved in the defense mechanism of the gastric mucosa in mice

“…Nonsteroidal anti-inflammatory drugs (NSAIDs) aggravate ethanol-caused gastric damage, 15,16 and it is well known that endogenous PGs may contribute to the mucosal defense mechanism by minimizing the damage. [17][18][19][20][21][22][23][24][25] We also found, in the present study, that NS-398, a selective COX-2 inhibitor, aggravated the 95% ethanol-caused gastric damage only in mice pretreated with acidified ethanol that showed COX-2 protein expression. These effects of NS-398 were similar to NSAID effects shown previously.…”

Prostaglandin protects isolated guinea pig chief cells against ethanol injury via an increase in diacylglycerol.

“…This PG action, which seems to be independent of their inhibitory action on gastric acid secretion, is referred to as cytoprotection (7). However, in addition to the mechanisms proposed, recently available evidence has suggested that PGs may also preserve the viability of not only gastric glands but also a homogeneous population of gastric cells exposed to noxious agents in vitro (8)(9)(10). Because PGs can directly interact with and protect gastric cells in the absence of mucus, blood flow, or bicarbonate, it is reasonable to speculate that PGs exert their protective effects presumably through activating intracellular processes.…”

Analysis of Localization of Adult T-cell Leukemia-derived Factor in the Transient Ischemic Rat Retina After Treatment with OP-1206 α-CD, a Prostaglandin E1Analogue

“…Because of these biological activities, PGE 1 and some of its analogues have been reported effective for treatment of obstructive diseases in various organs, including ischemic retinopathy (Heffelfinger et al 1987;Zygulska-Mach et al 1980;Carlson and Olsson 1976). Recent studies have shown that some types of prostaglandins, including PGE 1 , have cytoprotective activity against various noxious agents, ethanol, and taulocholic acid in cultured gastric cells (Cherner et al 1989;Tarnawski et al 1988;Lancaster and Robert 1978). On the basis of these findings, we hypothesized that, in ischemic retinopathy, PGE 1 may function as a tissue protector, accompanied by induction of ADF.…”