Effect of prostaglandin 15(R) 15 methyl-E2 methyl ester on aspirin and taurocholic acid-induced gastric mucosal haemorrhage in rats.

Abstract

SUMMARY The eflect of orally administered prostaglandin 15(R)15 methyl-E2 methyl ester on aspirin and taurocholic acid-induced gastric mucosal haemorrhage has been studied in rats. The incidence of haemorrhage induced by aspirin (26-7 mM), 64 mg/kg, together with taurocholic acid (2.5 mM), was significantly reduced from 53l6% to 19l5% by the addition of the prostaglandin (9-9 ,uM), P < 0 01. The incidence of haemorrhage induced by aspirin alone (53-3 mM), 128 mg/kg, was significantly reduced from 80% to 20% by the addition of prostaglandin (9-9 ,tM), P < 0-002.These results indicate the possible use of synthetic prostaglandins in the prevention of aspirininduced gastric pathology.It has long been known that aspirin ingestion in man produces gastric irritation which, on occasion, may progress to severe gastric erosions with haemorrhage. Semple and Russell (1975) have shown that the incidence of gastric mucosal bleeding induced by aspirin in rats is significantly increased by the addition of conjugated bile acids, especially taurocholic acid.Aspirin, in addition to other anti-inflammatory agents, has been shown to inhibit the synthesis of prostaglandins in vitro (Ferreira et al., 1971;Smith and Willis, 1971;Vane, 1971). Naturally occurring prostaglandins, especially El, E2, and A1, when given systemically, markedly inhibit gastric acid secretion in animals (Robert et al., 1967;Wilson and Levine, 1969) and in man (Classen et al., 1970;Wilson et al., 1971). Prostaglandin El has also been shown to inhibit the production of gastric ulceration in rats induced by stress after pyloric ligation (Robert et al., 1968). However, naturally occurring prostaglandins are rapidly degraded in the stomach when given orally and are largely ineffective by this route. In recent years, resistant synthetic analogues have been produced and can therefore be given orally with effect. Various workers have shown that certain of these analogues have an even greater 'Address for correspondence: Dr R. 1. Russell, Royal Infirmary, Glasgow, G4 OSF. Received for publication 20 October 1975 inhibitory effect on gastric secretion than the naturally occurring prostaglandins; this has been demonstrated in animals (Robert and Magerlein, 1973) and in man (Carter et al., 1973;Lippmann, 1974b). A more marked inhibitory effect has also been shown on gastric ulcer formation in the rat induced by indomethacin (Lippmann, 1974a) and by stress due to pyloric ligation (Carter et al., 1974).We have studied the effects of the synthetic analogue prostaglandin 15(R)15 methyl-E2 methyl ester on aspirin and taurocholic acid-induced gastric mucosal bleeding in rats.

Mechanisms Underlying Gastric Mucosal Damage Induced by Indomethacin and Bile‐salts, and the Actions of Prostaglandins

“…A 15-methyl analogue of prostaglandin E2 was previously found to inhibit the gastric erosions induced by taurocholate and a non-steroid antiinflammatory agent in -the rat (Carmichael et al, 1976). However, in that study the prevention of mucosal damage by intragastric administration of the (1 5R)-epimer, which could be converted to the potent gastric antisecretory (15S)-epimer in the acid environment (see Main & Whittle, 1975b), is likely to be the consequence of inhibition of the gastric acid secretion (Whittle, 1976a).…”

“…In the present study, changes in gastric mucosal blood flow and in the resistance of the mucosa to acid back-diffusion have been investigated as possible mechanisms underlying such acute erosion formation in the rat. In addition, since prostaglandin E2 methyl analogues can prevent this mucosal damage (Carmichael, Nelson, Russell, Chandra, Lyon & Cochran, 1976;Whittle, 1976a), the effects of the prostaglandin analogue on these parameters have also been studied. A preliminary account of this work has been presented to the British Pharmacological Society (Whittle, 1976b).…”

Protection of the rat gastric mucosa against aspirin injury by arachidonic acid: a dietary prostaglandin precursor fatty acid

“…animals and in man [l-141. One therapeutic modality which can reduce mucosal damage by aspirin is pretreatment with synthetic prostaglandins [ 1 1-1 3, [15][16][17]. Arachidonic acid (AA) is an essential dietary fatty acid which can be converted by the gastric mucosa to prostaglandins [ 181 and by this conversion is able to protect the gastric mucosa against alcohol injury [18,19].…”

Transcriptomics in Toxicogenomics, Part I: Experimental Design, Technologies, Publicly Available Data, and Regulatory Aspects

“…Unfortunately, even if the ENMs are removed by repeated wash-steps within the isolation procedure, the damage might have already been done when intracellular or cell membrane-bound ENMs interfere with the biological molecules that are used to assess toxicity [93]. ENMs could also remain within the cells, or bound to the cell membranes [69,94]. Again, the recommendation is to test for the unintended interactions and to also validate results with multiple techniques that use different detection methods.…”