Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cytoprotection”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources
PubMed1988

Cytoprotective activity of deboxamet: a possible interference with prostaglandin and prostacyclin metabolism in rat gastric mucosa.

Deboxamet (5-methoxy-2-methyl-3-indolyl-acetohydroxamic acid) is a new synthetic drug with anti-ulcer and anti-secretory activity. The authors evaluated the ability of deboxamet to protect the rat gastric mucosa against the intensive necroses induced experimentally by absolute ethanol, NaCl (25%), HCl (0.6 N), acetylsalicylic acid plus HCl, and sodium taurocholate plus HCl. Deboxamet, as compared with pirenzepine, sulglycotide and PGE2, displayed a cytoprotective activity against these necrotizing agents. The involvement of deboxamet with prostacyclin metabolism was also investigated. In order to assess the presence of PGI2-like substances, extracts of mucosa from rats treated orally with deboxamet and sulglycotide were assayed i) on isolated rabbit mesenteric artery, ii) for hypotensive effect in anaesthetized rat, and iii) for anti-platelet activity. Deboxamet, like sulglycotide, was able to raise the availability of prostacyclins in the rat gastric mucosa, which is an important action in maintaining its cellular integrity. However, our results cannot determine whether this activity is due to an enhanced biosynthesis or a decreased degradation of prostacyclins.

Animals↗
PubMed1987

Morphological and physiological effects of a cytoprotective prostaglandin analog (rioprostil) on the rat gastric mucosa.

This study was undertaken to investigate the ability of a cytoprotective synthetic primary alcohol PGE1 analog, rioprostil, to protect the rat gastric mucosa against topically applied 40% (v/v) ethanol. Use of an ex vivo gastric chamber model facilitated correlation of changes in dynamic physiological parameters (PD and net cation fluxes) with changes in mucosal structure. We were particularly interested in defining changes in mucosal structure which accompanied topical application of rioprostil and which might explain subsequent resistance to the effects of ethanol. Topical application of rioprostil for 10 min provided concentration-dependent protection against ethanol-induced hemorrhagic erosions. The most effective dose and concentration tested (25 micrograms rioprostil at a concentration of 10 micrograms/ml) completely prevented ethanol-induced lesion formation. Protection was not accompanied by significant preservation of the interfoveolar epithelium against ethanol, but did involve prevention of vasocongestion and limitation of damage to the superficial epithelium. Complete recovery of physiological parameters indicative of gastric mucosal barrier integrity occurred within 20 min. The most effective concentrations of rioprostil produced extensive subepithelial edema and, concurrently, significant increases in net efflux of sodium ions, decreases in mucosal PD, and loss of mucosal folding.

Administration, Topical↗
PubMed1988

Misoprostol and gastroduodenal mucosal protection (cytoprotection).

Misoprostol, a synthetic methyl analogue of prostaglandin E1 (PGE1), accelerates significantly the healing of duodenal and gastric ulcers in man. In addition to its acid antisecretory actions, misoprostol exhibits gastroduodenal mucosal protective (cytoprotective) effects in animals and in man against diverse damaging agents such as ethanol and non-steroidal anti-inflammatory drugs (NSAIDs). There are preliminary data indicating that misoprostol is superior to placebo and cimetidine in reducing mucosal damage secondary to the chronic administration of NSAIDs in man. Several studies indicate that patients with peptic ulcer disease secrete and/or produce less gastroduodenal prostaglandins that non-ulcer patients and thus may have a relative deficiency of mucosal prostaglandin synthesis. Ulcers are known to heal more slowly in cigarette smokers than non-smokers and have a higher rate of recurrence. There is also evidence that cigarette smoking inhibits gastric mucosal prostaglandin synthesis. Therefore smokers may also represent a group of individuals with depressed gastric mucosal prostaglandin synthesis, in addition to patients who consume NSAIDs. A preliminary study indicates that misoprostol may reverse the deleterious effect of smoking on duodenal ulcer healing.

Alprostadil↗
PubMed1988

Endogenous prostaglandin E2 synthesis preserved following cytoprotection by Roter (bismuth subnitrate) in the rat alcohol model of gastric ulceration.

The protective effect of the compound preparation Roter, principally bismuth subnitrate and the other base constituents of these tablets, magnesium carbonate and sodium bicarbonate, were assessed using the standard alcohol model of gastric ulceration in the rat. Groups of ten rats were studied with Group A as controls, Group B alcohol alone, Group C pretreatment with base components followed by alcohol, Group D pretreatment with bismuth subnitrate followed by alcohol and Group E pretreatment with full formulation Roter followed by alcohol. The study was assessed by measurement of areas of gastric ulceration and tissue prostaglandin E2 (PGE2) levels. Alcohol alone caused gross ulceration and reduction in PGE2 synthesis compared to controls (P less than 0.001). Pretreatment with tablet base gave only marginal protection whilst bismuth subnitrate gave marked protection against ulceration compared to alcohol alone (P less than 0.001). Full formulation Roter also gave marked protection against ulceration compared to alcohol alone (P less than 0.001) and this was associated with PGE2 synthesis indistinguishable from controls but significantly greater than in the alcohol alone group (P less than 0.001). It was not possible to determine whether the normal PGE2 synthesis was the cause or the result of protective effect of Roter and the accompanying reduction in ulceration. It was possible however to conclude that using this model of experimental ulceration. Roter and bismuth subnitrate are 'cytoprotective' and this was associated with the preservation of normal prostaglandin synthesis.

Animals↗
PubMed1988

Failure of a cytoprotective dose of Arbacet to heal acute gastric ulcers.

Twenty outpatients with an endoscopic diagnosis of gastric ulcer were evaluated for 6 wk in a randomized, double-blind trial comparing 15(R)-15-methyl prostaglandin E2 (Arbacet) (10 micrograms, 0.5 h before each meal and at bedtime) with placebo. Endoscopy was performed at 3 wk and 6 wk during the study period. Five of nine patients (56%) taking Arbacet and seven of 11 patients (64%) in the placebo group had complete healing of their gastric ulcer. Healing occurred in four patients from the Arbacet group and three patients in the placebo group at 3 wk. A cytoprotective dose of Arbacet (40 micrograms daily) is not significantly better than placebo in healing gastric ulcers.

Acute Disease↗
PubMed1987

Cytoprotection by sucralfate: role of sulfate ions.

Sucralfate and its component, sucrose octasulfate, are both SO4(2-)-containing compounds shown to protect against acid-peptic injury in rabbit and/or cat esophagi. To determine if sulfate ions (SO4(2-) contributed to this protection, a series of in vitro and in vivo experiments were performed in acid-exposed rabbit esophagi. In the Ussing chamber SO4(2-)-containing solutions significantly reduced the acid-induced decline in electrical resistance (R) observed in controls. This effect was unrelated to buffering of H+, accompanying cation or changes in luminal solution osmolality. Protection by SO4(2-) was specific since other divalent (HPO4(2-] or impermeant anions (gluconate-) failed to reduce the acid-induced decline in R. Protection was confirmed in vivo by showing that acid-perfused esophagi exposed to SO4(2-) had less morphologic damage, higher R and lower permeability to 14C-mannitol and H+ than controls. These results indicate that SO4(2-) have a unique protective action against acid injury to esophageal epithelia, and this action appears to explain the cytoprotective properties of sucralfate.

Animals↗
PubMed1986

Experimental basis for a role for sulfhydryls and dopamine in ulcerogenesis: a primer for cytoprotection--organoprotection.

This brief review presents the evolution of the concept of cytoprotection which was originally described by Robert (1979) to represent prevention of chemically induced hemorrhagic gastric erosions without inhibiting acid secretion. Prostaglandins (PG) and sulfhydryls (SH) protect only against deep hemorrhagic necrosis in the mucosa without altering the initial damage to surface epithelial cells. Organ integrity and function are thus maintained (i.e., organoprotection) despite the loss of several layers of mucosal cells. While both PG and SH are natural products it must be stressed that only SH compounds can enter directly into protective reactions (e.g., free radical scavenging, modification of receptor SH groups, oxidation of certain structural and enzyme proteins). In addition, SH compounds also stimulate PG synthesis. A major target of gastroprotection by either PG or SH is the preservation of mucosal microvasculature to maintain blood flow for rapid restitution and cell proliferation. Dopamine-related compounds are reviewed because of their possible role in duodenal ulceration. Dopamine and dopamine agonists are antiulcerogens in duodenal ulcer models. Dopamine antagonists are proulcerogens and the dopamine neurotoxin MPTP causes duodenal ulcer in experimental animals. The mechanism of duodenal antiulcerogenic effect involves inhibition of gastric acid and pepsin secretion, stimulation of duodenal bicarbonate secretion, correction of duodenal dysmotility, and maybe increased blood flow. Because of their multiple beneficial effects, SH compounds and dopamine drugs are good models for gastroenteroprotection.

Animals↗
PubMed1987

Gastric and duodenal antiulcer and cytoprotective effects of proglumide in rats.

Proglumide has been studied for its ability to inhibit gastric secretion and to protect the gastroduodenal mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, acetic acid, nonsteroid anti-inflammatory drugs, reserpine, cysteamine and the cytodestructing agents: 80% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl and 30 mg of acetylsalicylic acid in 0.35 M HCl in rats. The results of this study demonstrate that proglumide has both prophylactic and curative effects on various experimentally induced ulcers. It produced a dose-dependent inhibition of gastric secretion in the pylorus-ligated rats and reduced significantly the intensity of gastric lesions induced by pyloric ligation, hypothermic restraint stress, acetic acid, mucosal damaging agents and that of duodenal ulcers induced by cysteamine. The intensity of gastric lesions induced by nonsteroid anti-inflammatory drugs and reserpine was also reduced significantly by proglumide. Cimetidine, which was used as a standard antiulcer drug for comparison, also produced a similar protective effect in most of the models used by us. It was found to have a more potent antisecretory effect but failed to protect the rats against the gastric mucosal damage induced by hyperthermic restraint stress and 0.2 M NaOH. Our findings suggest that proglumide exerts these antiulcer effects by its antisecretory, gastric mucosal resistance increasing and cytoprotective activities. Further studies are required to find out its exact mechanism of action and therapeutic usefulness.

Animals↗
PubMed1979

Topical aspirin plus HCl gastric lesions in the rat. Cytoprotective effect of prostaglandin, cimetidine, and probanthine.

The effect of representative agents of three classes of antisecretory compounds; prostaglandins, histamine H2-receptor antagonist, and anticholinergic agents, on acute gastric mucosal lesions produced by topical aspirin (200 mg/kg) plus HCl (150 mM) in the pylorus-ligated rat was studied. Acid was given exogenously so as to negate any antisecretory effect of the drugs studied. Both nonantisecretory and antisecretory doses of each agent as determined by preliminary secretory studies were employed. The postaglandin analogue 16,16-dimethyl prostaglandin E2, the H2-receptor antagonist cimetidine, and the anticholinergic agent probanthine, in both doses studied, all significantly reduced lesion formation. The H1-receptor antagonist mepyramine neither protected by itself nor enhanced the protective effect of cimetidine. Pepsin release into the gastric content increased with increasing mucosal damage. However, addition of pepsin to the gastric instillate had no effect on severity lesions in any group, which indicates that the increased pepsin was the result of, and not the cause of, the mucosal damage. The findings indicate that all three classes of antisecretory agents studied are also cytoprotective, i.e., they can protect against gastric mucosal injury by topical aspirin plus HCl by some mechanism other than inhibition of acid and pepsin secretion.

Animals↗
PubMed1986

Gastric anti-ulcer and cytoprotective properties of 2-(3,4-dimethoxyphenyl)-5-methyl-thiazolidine-4-one in rat experimental ulcers.

Anti-ulcer properties of 2-(3,4-dimethoxyphenyl)-5-methylthiazolidine-4-one (KM-1146) were investigated on various experimental ulcers in comparison with cimetidine. While both KM-1146 and cimetidine at the same dose were comparative on the preventive effects of Shay- and stress-ulcers, KM-1146 was more effective against different necrotizing agents such as 0.2N NaOH and 99.5% ethanol at non-antisecretory dose. KM-1146 50 mg significantly accelerated the healing of acetic acid-induced ulcers while cimetidine 200 mg had no effect. KM-1146 increased rat gastric mucosal blood flow as measured by hydrogen gas clearance and prevented a decrease of gastric mucus gel thickness induced by water immersion restraint stress. These studies indicate that KM-1146 exerts cytoprotective action even in anti-secretory dose in addition to a significant anti-ulcer action which is comparable to cimetidine.

Acetates↗
PubMed1985

Cytoprotective therapy of gastric ulcers: a controlled clinical evaluation of triletide versus carbenoxolone.

Two parallel groups, each of 10 out-patients with endoscopically confirmed benign gastric ulcer, were randomly assigned to receive either 1.5 g/day of triletide, a new tripeptide shown to increase the synthesis of gastroduodenal mucus and to antagonize thromboxane A2, or 0.3 g/day of carbenoxolone. Both drugs were given orally in 3 divided doses for 4 weeks, according to the controlled design. Endoscopy showed that a greater proportion of patients treated with triletide benefited from treatment (60%) in comparison with those who had carbenoxolone (40%), but the difference was not significant. Weekly monitoring of epigastric pain, heartburn and antacid intake showed both treatments to be effective, and triletide to be overall faster acting (p less than 0.01 for epigastric pain). Subjective complaints of possible side-reactions were not recorded with either treatment; routine physical examination, haematology and haematochemistry remained unaffected by triletide, whereas treatment with carbenoxolone was associated with a significant increase in both systolic and diastolic blood pressure and with a significant decrease (p less than 0.05) in blood potassium levels. Triletide, therefore, appeared to be an effective and well-tolerated means for the therapy of gastric ulcer, and by virtue of its significantly greater symptomatic action and greater tolerance in comparison with a standard cytoprotective treatment such as carbenoxolone, it is suggested that triletide deserves consideration in the management of peptic ulcer.

Adult↗
PubMed1986

Cytoprotective effects of Bencianol on porcine vascular endothelial cells in vitro.

Endothelial cells of porcine thoracic aorta were chosen as in vitro model to study the reaction of endothelial cells to injury induced by carbon tetrachloride (CCl4 0.2 microliter/ml). Lactate dehydrogenase (LDH) was used as the biochemical marker of cell injury. The changes in the morphology of the surface endothelial cells were observed by scanning electron microscopy. In addition, cell survival rate after replating cultures was evaluated. The pretreatment with Bencianol (10(-10) M-10(-7) M) produced cytoprotective effects against CCl4 induced cell injury on the above three parameters.

Animals↗
PubMed1984

Interrelationships between the membrane-bound ATP-dependent energy systems of the gastric mucosa and the gastric cytoprotective effect of beta-carotene on the development of gastric mucosal damage produced by 0.6 M HCl in rats.

The effects of different doses (0.01-0.1-1.0-10.0/mg/kg-1) of beta-carotene were studied on gastric secretory responses of 4 hr pylorus-ligated rats: development of gastric mucosal damage (as assessed by number and severity of lesions) produced by intragastric administration of 0.6 M HCl; tissue level of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenylate pool (ATP + ADP + AMP), ratio of ATP X ADP-1, "energy charge" (ATP + 0.5 ADP X X (ATP + ADP + AMP)-1) (during the development of gastric mucosal damage by 0.6 M HCl and of gastric cytoprotection by beta-carotene. It was found that beta-carotene did not decrease the gastric secretory responses of 4 hr pylorus-ligated rats; The development of gastric mucosal damage could be decreased dose-dependently by the administration of beta-carotene; the ATP transformation could be decreased by beta-carotene; the tissue levels of cAMP and AMP could be increased significantly and dose-dependently by beta-carotene; the ratio of ATP X ADP-1 could be increased significantly and dose-dependently by beta-carotene; the values of adenylate pool and "energy charge" remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1983

[Serotonin participation in the mechanism of the cytoprotective action of polyglucin on the stomach].

Experiments on rats with the use of ultrastructural analysis and fluorescent-histochemical and biochemical methods have shown serotonin to participate in the mechanism of the cytoprotective effect of polyglucin on the stomach. In the presence of experimental hyperthyrosis, intravenous injection of polyglucin coupled with hydrocortisone reduces the percentage of gastric mucosa lesions. This is a consequence of the restriction of serotonin release from serotonin-producing gastric cells.

Animals↗
PubMed1983

Cytoprotective effect of prostacyclin and protein synthesis.

It is shown that de novo synthesis of protein is essential for the healing process of experimental gastric ulcer and that the cytoprotective effect of prostacyclin is connected with protein synthesis. In preliminary experiments the influence of prostacyclin on hepatic protein synthesis has also been shown.

Animals↗
PubMed1983

Gastric cytoprotection by agents altering gastric mucosal sulfhydryl compounds: role of endogenous prostaglandins.

Intragastric administration of cysteamine or diethyl maleate caused a dose-dependent reduction in the mean area of gastric lesions induced by absolute ethanol but failed to affect gastric ulcerations produced by acidified aspirin. Mucosal levels of glutathione were increased with cysteamine and reduced with diethyl maleate and did not correlate with the protective action of these agents on ethanol-induced mucosal lesions. The protective effects of these agents probably involved mucosal generation of prostaglandins, because pretreatment with indomethacin or aspirin, potent inhibitors of cyclooxygenase, partially prevented this protection. This study indicates that the mucosal generation of prostaglandins contributed, at least in part, to the gastric cytoprotection by agents altering mucosal contents of sulfhydryl compounds.

Animals↗
PubMed1984

Effects of capsaicin on the development of gastric mucosal damage by different necrotizing agents and of gastric cytoprotection by PGI2 atropine and cimetidine on rats.

Capsaicin desensitization was used as a tool to reveal the role of neurogenic inflammation in the gastric mucosal lesions induced by intragastric application of four different noxious chemical agents (96% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl). In capsaicin desensitized rats the number of lesions did not differ from that of the controls one hour after the application. There was, however, a significant reduction in the severity of the mucosal damage. These findings provide the first evidence for the participation of neurogenic inflammation in the gastric mucosal damage induced by aggressive chemicals. Gastrocytoprotection induced by prostacyclin (PGI2, 5 micrograms/kg), atropine (25 micrograms/kg) or cimetidine (2.5 mg/kg) was not inhibited in capsaicin desensitized rats. The number of lesions was not altered, while the severity of damage was more effectively reduced in the desensitized group. These findings indicate that the cytoprotective effect of these drugs is not mediated through capsaicin-sensitive sensory-efferent local tissue reactions.

Animals↗
PubMed1983

[Sucralfate (Ulcogant). The mechanism of action of a cytoprotective agent].

The new antiulcer drug sucralfate is characterized by a multiple mode of action. Its predominant feature is a protection of the mucosa from endogenous and exogenous noxious agents. These cytoprotective properties result from a locally formed layer covering ulcers and erosions which inhibits the diffusion of H-ions and pepsin to the damaged mucosa. This layer is also stable against exogenous substances with deleterious effects on the mucosa like alcohol and salicylates. Furthermore, sucralfate binds pepsin and bile acids. Recently, a stimulating effect of sucralfate on the release of prostaglandins and the regeneration of epithelial cells in the gastric mucosa was demonstrated. There is no influence of sucralfate on the production of gastric juice and pH. Since sucralfate is minimally absorbed it is a safe and well tolerated drug.

Adsorption↗