Effect of mild irritant on gastric mucosal offensive and defensive factors.

The effect of hypotonic medium (Distilled water: DW) and hypertonic saline (HS: 5% NaCl) compared to control normal saline (NS) was studied on gastric ulcer induced by aspirin, 6 h cold restraint stress, ethanol, and pylorus ligation in rats. DW did not afford any protection while HS showed significant ulcer protective effects in all gastric ulcer models studied. The cytoprotective effect of HS seemed to be not only due to its effect on gastric acid secretion but also its effect on mucosal defensive factors like enhanced mucin secretion and decreased cell shedding. As determined by radioimmunoassay, DW did not produce any change in the accumulation of PGE and PGI2, while HS increased them significantly in the human gastric mucosal incubates compared to NS. However, in the incubates of human colonic mucosa, both DW and HS showed a significant increase in PGE with a tendency to increase in PGI2 accumulation.

Effect of GABA and baclofen on gastric mucosal protective factors.

GABA and baclofen (BAC), a GABA-mimetic agent, were investigated for antiulcerogenic activity. Orally administered GABA (100 mg/kg) and BAC (10 mg/kg) showed significant ulcer protection when given either alone for one day or for 4 days, or when given together with aspirin (ASP; 200 mg/kg x 3 days) in their 4 days treatment time in pylorus-ligated rats. Both the drugs showed a tendency to increase acid and decrease peptic output, and increased gastric mucus secretion in terms of total carbohydrate to protein ratio (TC:P) in both the above treatment groups. ASP tended to decrease acid and increase peptic output and significantly decreased TC:P ratio. Both GABA and BAC tended to reverse aspirin-induced effects, though they had little per se effect on TC:P ratio of gastric mucosal glycoproteins except an increase in sialic acid content both after one day or four days treatment. No, per se, effect on cell shedding (DNA and protein content of gastric juice) or cell proliferation (DNA/mg protein) was noted with GABA or BAC but the enhanced cell shedding induced by ASP was attenuated by them. ASP was found to enhance cell proliferation. However, neither of drug showed any effect on cell proliferation when given either alone or in combination with ASP. The antiulcerogenic effect of GABA and BAC may be due to their predominant effects on mucosal defensive factors like enhanced mucin secretion and decreased cell shedding or mucosal damage.

Antiulcer activity of naturally occurring pyrano-coumarin and isocoumarins and their effect on prostanoid synthesis using human colonic mucosa.

Oral administration of bergenin and norbergenin, two isocoumarins, isolated from the leaves and roots of Flueggea microcarpa and luvangetin, a pyranocoumarin isolated from the seeds of Aegle marmelos Correa, showed significant protection against pylorus-ligated and aspirin-induced gastric ulcers in rats and cold restraint stress-induced gastric ulcers in rats and guinea pigs. The study on prostaglandins release by human colonic mucosal incubates, indicated a concentration-dependent (1-10 micrograms/ml) stimulatory effect of bergenin and norbergenin, while luvangetin (1-10 micrograms/ml) did not produce any effect. The results suggest that gastroprotective effects of bergenin and norbergenin could be due to increased prostaglandin production while, some other mucosal defensive factors may be involved for luvangetin.

Effect of some Sitavirya drugs on gastric secretion and ulceration.

Four Sitavirya plants viz. Satavari (fresh root juice, 1250 mg/kg), Yastimadhu (water decoction of root, 600 mg/kg), Kutaja and Aswattha (water decoctions of bark; 400 and 500 mg/kg respectively) were studied for their effects on different models of gastroduodenal ulcers in rats, when given orally for 3 days. All of them were found to protect the animals against 2 hr cold restraint stress and pylorus ligation-induced gastric and cysteamine-induced duodenal ulcers. However, they were ineffective against acute aspirin-induced gastric ulcers. The antiulcerogenic effect could be due to their inhibitory effect on offensive acid-pepsin secretion and augmentation of mucosal defensive factors in terms of enhanced mucin secretion and decreased cell shedding.

Effect of withafastuosin E on gastric mucosal offensive and defensive factors in rats.

Withafastuosin E (WE), a withanolide of Datura fastuosa, has been reported to possess anti-stress activity and augment prostaglandins. The present investigation has been undertaken to evaluate the anti-ulcer activity and its mechanism in various models of experimentally induced ulcers in rats. WE (20 mg/kg, po) reduced the incidence of ulcer and ulcer index significantly in rats. The drug also decreased volume of gastric secretion, acid and peptic output, though it did not affect mucin secretion or mucosal glycoprotein content in terms of total carbohydrate:protein ratio or gastric cell shedding (in terms of gastric juice DNA content) or cell replication (in terms of microgram DNA/mg of protein). The results suggest significant anti-ulcer activity of WE which may be due to its effect on decreasing the offensive acid-pepsin factors.

Effect of continuous infusion of GABA and baclofen on gastric secretion in anaesthetised rats.

Continuous infusion of gamma- aminobutyric acid (GABA) and baclofen (BAC) on gastric acid and pepsin secretion in perfused rat stomach showed that GABA (25-100 mg/kg/hr, i.v.) and BAC (1 mg/kg/hr, i.v.) increased the acid output which was blocked by bicuculline (Bicc, 1 mg/kg, i.v.) when given 30 min before their infusion. However, lower dose of GABA (5 mg/kg/hr) and hig her doses of BAC (5 or 10 mg/kg/hr) did not show any significant effect on acid secretion. GABA (5 and 25 mg/kg/hr) inhibited peptic output and again Bicc in the above dose inhibited the inhibitory effect of 25 mg/kg/hr of GABA on peptic output. The result indicate dichotomy on the effects of GABA on acid and pepsin secretion. As both the effects were blocked by Bicc, involvement of GABAA receptor may be a possibility. The antiulcer effect of GABA and BAC could not be due to their effect on gastric acid secretion, but may be due to inhibition of pepsin secretion by GABA or effects of GABA or BAC on mucosal defensive factors.

Anti-ulcerogenic activity of GABA and GABA mimetic agents in rats.

To elucidate the involvement of peripheral gamma- aminobutyric acid (GABA) and some GABA-mimetic agents in different models of gastric and duodenal ulcerations in rats and guinea pigs, effects of GABA, baclofen (GABAB agonist), diazepam, gamma-butyrolactone (GABA receptor agonist), sodium valproate, isoniazid (GABA-T inhibitor) and glycine (an inhibitory neurotransmitter), given po or ip were studied. All the drugs significantly reduced the ulcer index, incidence and number of ulcer in various models of gastric ulcers except glycine which failed to protect in reserpine-induced ulcers in rats. None of the drugs, except diazepam, had any protective effect on histamine-induced gastric ulcers in guinea pigs. Similarly, no protection was observed by any drug against cysteamine-induced duodenal ulcers in rats, while sodium valproate, isoniazid and glycine significantly decreased number of ulcers against histamine-induced duodenal ulcer in guinea pigs. The results suggest that GABA and GABA-mimetic agents, and glycine, an inhibitory neurotransmitter, afforded protection against some experimental models of peptic ulcer in rats. The effects appear to be due to their inhibitory effect on mucosal defensive factors.

Effect of graded doses of methysergide on basal and pentagastrin stimulated gastric secretion in anaesthetised rats.

The effect of continuous infusion (iv) of graded doses of methysergide (0.1-50 microgram(s)/kg/hr) was studied on basal and pentagastrin (5 microgram(s)/kg/hr) stimulated gastric acid secretion in anaesthetised rats by the slow, continuous stomach perfusion method. Both basal and pentagastrin stimulated acid secretion indicated a biphasic response. Methysergide induced stimulation at a lower dose of 1 microgram(s)/kg/hr and inhibition at higher doses of 20-50 microgram(s)/kg/hr. The stimulatory effect may be due to postsynaptic receptor blockade while the inhibitory effect at higher dose may be due to blockade of presynaptic 5-HT autoreceptors, or due to a direct inhibitory effect of unknown basis.

Effect of Tamrabhasma, an Indian indigenous preparation of copper, on rat gastric mucosal resistance.

Tamrabhasma (TMB), an Indian indigenous preparation of copper, was studied for its effects on factors related to rat gastric mucosal resistance. Rats of either sex treated with TMB (2.5 mg/kg po, twice daily for 3 days) showed (i) increased mucosal sialomucin and fucose contents; (ii) decreased gastric juice DNA and protein; and (iii) no change in DNA and the incorporation of [3H]-thymidine in to mucosal cell DNA. aspirin treatment decreased both the sialomucin and fucose contents, and increased DNA and incorporation of [3H]-thymidine in to mucosal cell DNA. However, aspirin increased gastric juice DNA and protein contents. Since gastric juice DNA and the incorporation of [3H]-thymidine into mucosal cell DNA indicate the rate of mucosal shedding and cell proliferation, the results indicate ways in which TMB may increase gastric mucosal resistance to damage.