Mechanisms of Protection by Omeprazole against Experimental Gastric Mucosal Damage in Rats

The effects of graded doses of verapamil on ethanol-induced stomach mucosal damage were studied in rats. Gastric lesions were induced in vivo by oral administration of 80% ethanol and evaluated with regard to ulcer index, gastric mucus content, free and total acidity, lipid peroxidation and nonprotein sulfhydryl groups. Orally administered ethanol markedly increased the ulcer index and lipid peroxidation. Pretreatment of rats with verapamil (1, 5, and 25 mg/kg i.p.) was carried out 1 h before the administration of ethanol. Verapamil showed a protective effect against ethanol-induced mucosal damage only at high dose (25 mg/kg). Verapamil dose dependently decreased the total acidity, lipid peroxidation, and nonprotein sulfhydryl content. Verapamil 25 mg/kg also increased significantly the gastric mucus secretion. L-arginine (100 mg/kg) or L-nitroarginine (100 mg/kg) with verapamil were also administered to the animals to determine the role of nitric oxide in the mechanism of the gastroprotective activity of verapamil (25 mg/kg). The results indicate that reduced acidity and lipid peroxidation and increased mucus secretion participate in the protective effects of verapamil against ethanol damage. On the other hand, a decrease in the nonprotein sulfhydryl content was observed with decreased gastroprotective effects of verapamil.

show abstract

“…1,22) Gastric mucus plays an important role in the pathophysiology of acute mucosal damage following the application of necrotizing agents.…”

Section: Discussionmentioning

confidence: 99%

Dose-Dependent Effects of Verapamil on Ethanol-Induced Gastric Lesions in Rats

Kılıç

Sırmagül

Batu

et al. 2006

JOURNAL OF HEALTH SCIENCE

View full text Add to dashboard Cite

show abstract

“…route 30 min before the induction of gastric mucosal damage. The doses of proton pump blockers tested in the present study were selected on the basis of their efficacy in reducing gastric acid secretion and counteracting acute mucosal damage induced by necrotizing agents [6,161. Since pantoprazole and omeprazole show different degrees of lability under acidic conditions [16], the i.d.…”

Section: Animals and Drug Treatmentmentioning

confidence: 99%

Gastroprotective effects of pantoprazole against experimental mucosal damage

Blandizzi

Natale

Gherardi

et al. 2000

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

The present study investigated the gastroprotective effects of the proton pump inhibitor pantoprazole on gastric mucosal damage induced by ethanol-HCl in rats. Omeprazole was used as reference drug. The morphometric analysis of gastric histological sections revealed that pantoprazole and omeprazole dose-dependently prevented the necrotic mucosal injury evoked by ethanol-HCl (ED50 = 14.1 and 21.6 micromol/kg, respectively). These effects were associated with a marked increment of Alcian blue recovery from gastric bound mucus (ED50 = 18.8 and 29.3 micromol/kg, respectively). In addition, both pantoprazole and omeprazole inhibited gastric acid secretion in pylorus-ligated rats (ED50 = 1.5 and 3.3 micromol/kg, respectively). Further experiments indicated that the protective effects of pantoprazole were not modified by L-365,260 (a gastrin receptor antagonist), suramin (a drug able to interfere with endogenous growth factors), N(G)-nitro-L-arginine (an inhibitor of nitric oxide synthase) or systemic ablation of capsaicin-sensitive sensory nerves, whereas they were partly blocked by indomethacin (an inhibitor of prostaglandin synthesis) and fully prevented by N-ethylmaleimide (a potent blocker of sulfhydryl compounds). The present data provide histomorphometric evidence that: 1) pantoprazole is endowed with gastroprotective properties and is more active than omeprazole in preventing the necrotic mucosal damage induced by ethanol-HCl; 2) according to the rank order of ED50 values, the protective effects of both drugs appear to depend mainly on the enhancement of the gastric mucosal barrier rather than on the inhibition of acid secretion; 3) an increased production of prostaglandins, as well as an increased availability of sulfhydryl radicals at the level of the gastric mucosa may account for the gastroprotective effects of pantoprazole.

show abstract

“…16 Moreover, proton pump inhibitors, including lansoprazole, have been reported to protect the gastric mucosa against ethanol-HCl-induced injury which is minimally influenced by intragastric acid. [17][18][19][20][21] Furthermore, rabeprazole has been shown to suppress ethanol-induced gastric lesions. 22 However, in the clinical setting, drugs are administered in order to repair gastric lesions, not to protect against the development of lesions.…”

Section: Introductionmentioning

confidence: 99%

Effects of Sucralfate, Cimetidine and Rabeprazole on Mucosal Hydroxyproline Content in Healing of Ethanol–hcl‐induced Gastric Lesions

Arisawa¹,

Shibata²,

Kamiya³

et al. 2006

Clin Exp Pharma Physio

View full text Add to dashboard Cite

1. No general consensus has been reached on the treatment of acute gastric lesions. The aims of the present study were to clarify the effects of sucralfate, cimetidine and rabeprazole monotherapies and combination therapies on acute gastric lesions from the viewpoint of connective tissue regeneration. 2. Gastric lesions were experimentally created by the oral administration of 50% ethanol-0.15 mol/L HCl to rats. After 30 min, the anti-ulcer agents sucralfate (100 mg/kg), cimetidine (20 mg/kg) and rabeprazole (2 mg/kg) were administered separately or in combination and the stomach was excised at different times to measure the level of hydroxyproline in the gastric mucosa and determine lesion index. Immunostaining against prolylhydroxylase was performed on some specimens. 3. In the control group, lesion index decreased linearly from 30 min after ethanol-HCl administration and the level of mucosal hydroxyproline peaked between 2 and 4 h later. Although sucralfate significantly promoted lesion healing, it had no effect on mucosal hydroxyproline level. Cimetidine suppressed increases in mucosal hydroxyproline and prolonged lesion healing, but these findings were reversed by combining cimetidine and sucralfate. Rabeprazole had no significant effect on lesion healing, but promoted lesion healing in combination with sucralfate. Immunohistochemical analysis showed that prolylhydroxylase was expressed in spindle cells that lined the glandular cells in a boundary area between normal and injured tissues. 4. Under conditions in which the effects of intragastric pH are minimal, sucralfate is superior to antisecretory agents in promoting the healing of acute gastric lesions.

show abstract

Mechanisms of Protection by Omeprazole against Experimental Gastric Mucosal Damage in Rats

Cited by 28 publications

References 18 publications

Dose-Dependent Effects of Verapamil on Ethanol-Induced Gastric Lesions in Rats

Dose-Dependent Effects of Verapamil on Ethanol-Induced Gastric Lesions in Rats

Gastroprotective effects of pantoprazole against experimental mucosal damage

Effects of Sucralfate, Cimetidine and Rabeprazole on Mucosal Hydroxyproline Content in Healing of Ethanol–hcl‐induced Gastric Lesions

Contact Info

Product

Resources

About