Leminoprazole Protects Cultured Gastric Mucosal Cells against Damage Caused by Ethanol, Indometacin and Taurocholate

Takahashi, Satoru; Yamazaki, Takashi; Okabe, Susumu

doi:10.1159/000139478

Cited by 5 publications

(2 citation statements)

References 14 publications

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“…Several lines of evidence indicate that, beside the marked inhibition of gastric acid secretion, the antiulcer effects of benzimidazole derivatives may depend on acid-independent protective actions (Blandizzi et al, 1999a;Kawano et al, 1992;Takahashi et al, 1997). In the present study, the gastroprotective properties of lansoprazole were assayed in a model of gastric injury elicited by intraluminal application of ethanol and HCl, and the histomorphometric analysis of gastric mucosa clearly demonstrated that this drug significantly prevent the occurrence of the most severe types II and III lesions.…”

Section: Discussionmentioning

confidence: 52%

Mechanisms of gastroprotection by lansoprazole pretreatment against experimentally induced injury in rats: role of mucosal oxidative damage and sulfhydryl compounds

Natale

Lazzeri

Lubrano

et al. 2004

Toxicology and Applied Pharmacology

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Section: Discussionmentioning

confidence: 52%

Mechanisms of gastroprotection by lansoprazole pretreatment against experimentally induced injury in rats: role of mucosal oxidative damage and sulfhydryl compounds

Natale

Lazzeri

Lubrano

et al. 2004

Toxicology and Applied Pharmacology

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“…Furthermore, leminoprazole protects the gastric mucosa against various ulcerogenic stimuli, such as ethanol, indomethacin and water-immersion restraint. The protective effect of leminprazole is considered to be through its antisecretory effect, mucus synthesis-promoting effect, and direct cytoprotec- Takahashi/Okabe tive effect on gastric epithelial cells [1,[3][4][5][6][7][8][9][10]. It was reported that accumulation of mucus glycoproteins in the gastric mucosa is observed after the oral administration of leminoprazole to rats [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Mechanism by Which Orally Administered Leminoprazole Stimulates Mucus Synthesis in Rats

Takahashi

Okabe²

1998

Pharmacology

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We examined the mechanism by which leminoprazole (an acid pump inhibitor) stimulates mucus synthesis in rats. Leminoprazole and omeprazole were administered to rats, and then the gastric fragments were isolated from the fundus of their stomachs. Mucus synthesis was assessed by [³H]leucine and [³H]glucosamine incorporation by the fragments into high-molecular-weight materials. After oral administration of leminoprazole, mucus synthesis by the gastric fragments was dose-dependently stimulated, while acid secretion was inhibited. Omeprazole had no effect on mucus synthesis, although it potently inhibited acid secretion. Treatment with N^G-nitro-L-arginine methyl ester (L-NAME), but not indomethacin, caused a reduction of leminoprazole-stimulated synthesis of gastric mucus in a dose-dependent manner. The inhibitory action of L-NAME was restored by the concomitant administration of L-arginine, but not D-arginine. Intragastric administration of leminoprazole to pylorus-ligated rats also stimulated mucus synthesis without inhibiting acid secretion. In contrast, in the case of intraperitoneal administration, leminoprazole exerted a potent antisecretory effect, but failed to promote mucus synthesis. Exposure of leminoprazole to the luminal surface of the gastric mucosa did not cause any damage. We conclude that orally administered leminoprazole, via direct effect toward the gastric mucosa, stimulates mucus synthesis in rats probably through nitric oxide mediation. The stimulatory effect of leminoprazole on mucus synthesis is independent of its antisecretory effect.

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Protective effects of proton pump inhibitors against indomethacin-induced lesions in the rat small intestine

Pozzoli

Menozzi

Grandi

et al. 2006

Naunyn-Schmied Arch Pharmacol

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Proton pump inhibitors (PPIs) have been shown to be effective in preventing gastric and duodenal ulcers in high-risk patients taking nonsteroidal anti-inflammatory drugs (NSAIDs); by contrast, scarce information is available concerning the effects of PPIs on intestinal damage induced by NSAIDs in humans or in experimental animals. We examined the effects of lansoprazole and omeprazole on the intestinal injury induced by indomethacin in the conscious rat. PPIs were administered by the intragastric route at 30, 60 and 90 micromol/kg, 12 h and 30 min before and 6 h after indomethacin treatment. The effects of omeprazole and lansoprazole were evaluated on: (1) macroscopic and histologic damage; (2) mucosal polymorphonuclear cell infiltration; (3) oxidative tissue damage and (4) bacterial translocation from lumen into the intestinal mucosa. Lansoprazole and omeprazole (at 90 micromol/kg) significantly decreased (P<0.01) the macroscopic and histologic damage induced by indomethacin in the rat small intestine. Furthermore, both drugs greatly reduced (P<0.01) the associated increases in myeloperoxidase levels and lipid peroxidation induced by indomethacin, whereas they only moderately affected (P<0.05) the translocation of enterobacteria from lumen into the intestinal mucosa. These data demonstrate that omeprazole and lansoprazole can protect the small intestine from the damage induced by indomethacin in the conscious rat. The intestinal protection, possibly related to antioxidant and anti-inflammatory properties of these drugs, may suggest new therapeutic uses of PPIs in intestinal inflammatory diseases.

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Leminoprazole Protects Cultured Gastric Mucosal Cells against Damage Caused by Ethanol, Indometacin and Taurocholate

Cited by 5 publications

References 14 publications

Mechanisms of gastroprotection by lansoprazole pretreatment against experimentally induced injury in rats: role of mucosal oxidative damage and sulfhydryl compounds

Mechanisms of gastroprotection by lansoprazole pretreatment against experimentally induced injury in rats: role of mucosal oxidative damage and sulfhydryl compounds

Mechanism by Which Orally Administered Leminoprazole Stimulates Mucus Synthesis in Rats

Protective effects of proton pump inhibitors against indomethacin-induced lesions in the rat small intestine

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