Gastric Cytoprotection by Tetraprenylacetone in Human Subjects

Yamada, Hiroaki; Nakamura, Atsushi; Nebiki, Hiroko; Satoh, Hiroshi; Fukuda, Takashi; Nakamura, Hajime; Kobayashi, Kenzo

doi:10.1159/000199613

Cited by 20 publications

(12 citation statements)

References 8 publications

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“…We reported previously that pretreatment with TPA can prevent gastric damage induced by absolute ET, and this action of TPA may be due to the stimulation of gastric mucus production (7,8). Arakawa et al demonstrated the protective effect of TPA against gastric injury caused by ET in human subjects (9). Further, it has been reported that this effect of TPA may involve the metabolism of mucosal lipids (10)(11)(12).…”

Section: Discussionmentioning

confidence: 91%

Tetraprenylacetone promotes healing process of ethanol-induced gastric damage in the rat.

et al. 1991

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ABSTRACT-Tetraprenylacetone (TPA: teprenon, geranylgeranylacetone) is a novel anti-ulcer agent developed in Japan. The aim of this study was to test whether TPA has the ability to promote the healing process of rat gastric mucosal injury induced by absolute ethanol (ET). Fasted rats received orally 5 ml/kg of absolute ET . Sixty minutes later, TPA (200 mg/kg) or saline (control) was administered intragastrically . Thereafter, the same dose of TPA or saline was given orally every 8 hours. To investigate the role of endogenous prostaglandins, indomethacin was given intraperitoneally every 8 hours. Twenty four or 48 hours after the first administration of TPA or saline, rats were sacrificed and the stomachs were removed. Administration of TPA significantly reduced lesion indices from 100 ± 12.9% (control) to 57.0 ± 12.8% (24 hours, P < 0.05) and from 100 ± 15.3% (control) to 17.6 ± 3.4% (48 hours, P < 0.01). Addition of indomethacin did not significantly affect this effect of TPA . Ultrastructual studies revealed that TPA stimulated regeneration of gastric mucosa damaged by ET after 24 and 48 hours. These results indicate that TPA has the ability to promote the healing process of gastric mucosal damage induced by absolute ET. It is, however, unlikely that endogenous prostaglandins are involved in this promotive effect of TPA on the healing process of gastric injury.

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Section: Discussionmentioning

confidence: 91%

Tetraprenylacetone promotes healing process of ethanol-induced gastric damage in the rat.

et al. 1991

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“…In experimental studies, it prevents or reduces experimental gastric lesions induced by cold-resistant stress, indomethacin, or taurocholic acid/HCl and pro tects isolated gastric mucosal cells by mechanisms other than acid inhibition [18][19][20][21][22][23]. The clinical relevance of this agent is underscored by the fact that protective action of teprenone also applies to the human gastric mucosa [24][25][26], Teprenone enhances the synthesis of PGE2, the pro duction of which is impaired in portal hypertension [12][13][14][15][16]. Of relevance to study is the fact that teprenone increases the production of gastric mucus in the normal gastric mucosa.…”

Section: Discussionmentioning

confidence: 99%

Effect of Teprenone on Portal Hypertensive Gastric Mucosa

et al. 1996

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Teprenone (geranylgeranylacetone) is a gastric mucosal protective drug used clinically in Japan for treatment of gastric ulcers and gastritis. Its effect on portal hypertensive (PHT) gastric mucosa which has impaired defensive mechanisms is not known. In 20 PHT and 20 sham-operated rats, we studied the effects of teprenone or placebo on: (1) portal pressure; (2) gastric pH; (3) gastric mucosal blood flow using laser Doppler flowmetry, and (4) hexosamine content in gastric mucosa. The gastric mucosal blood flow was significantly higher in the PHT + teprenone group than in the PHT + placebo group (463 ± 75 and 381 ± 82 perfusion units, respectively; p < 0.05). The hexosamine content was significantly lower in PHT rats than in sham-operated controls (12.6 ± 2.3 vs. 14.3 ± 2.2 μg/mg, respectively). Teprenone treatment significantly increased the gastric mucosal hexosamine concentration in both sham-operated and PHT rats (17.2 ± 3.1 and 15.6 ± 3.6 μg/mg, respectively). These effects of teprenone, combined with its known prostaglandin-stimulat-ing action, suggest a potential role for this agent in the treatment of PHT gastric mucosal abnormalities.

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“…Furthermore, gastric cancer shows major substitution of MUC5AC and MUC6 by MUC3 and MUC4 (10-12, 15, 16, 18). Because the differential expressions of gastric MUC types have not been evaluated in terms of the protective role of the mucin, we tried to identify the MUC type that plays a major role in a rat model of ethanol-induced gastric mucosal damage by using geranylgeranylacetone (GGA), a cytoprotective agent (19)(20)(21). GGA is an acyclic polyisoprenoid and an antiulcer drug developed in Japan (22).…”

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confidence: 99%

Gastric Mucosal Protection via Enhancement of MUC5AC and MUC6 by Geranylgeranylacetone

et al. 2005

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The mucus layer that covers gastric mucosa is a powerful barrier that protects tissues from the hazardous gastric environment; however, the role of each gastric MUC type, such as MUC1, MUC5AC, and MUC6, has not been evaluated. The purpose of this study is to identify the MUC type, which plays a predominant role in this protective process by use of geranylgeranylacetone (GGA), a promising cytoprotective agent. In addition, the mechanism of mucus secretion promoted by GGA was investigated. Rat gastric mucosal damage was provoked using ethanol, and GGA was pretreated 1 hour before ethanol. GGA was found to significantly protect rats from ethanol-induced gastric damage by increasing mucus levels, MUC5AC and MUC6, especially at ethanol-induced ulcer margins, but not by MUC1. When expression of heat shock protein 70 (HSP70) and neuronal nitric oxide synthase (nNOS) was evaluated by Western blotting, both were found to be increased in GGA-treated ethanol rats. In addition, the cytoprotective effect of GGA was blocked by L-NMMA, a nonspecific NOS inhibitor, but not blocked by aminoguanidine, a specific inducible nitric oxide synthase inhibitor, thus indicating the participation of nNOS. In conclusion, GGA protected ethanol-induced gastric damage by upregulating MUC5AC and MUC6 rather than MUC1. In addition, HSP70 and nNOS were found to be involved in GGA cytoprotection, probably by increasing mucus production or secretion.

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Gastric Cytoprotection by Tetraprenylacetone in Human Subjects

Cited by 20 publications

References 8 publications

Tetraprenylacetone promotes healing process of ethanol-induced gastric damage in the rat.

Tetraprenylacetone promotes healing process of ethanol-induced gastric damage in the rat.

Effect of Teprenone on Portal Hypertensive Gastric Mucosa

Gastric Mucosal Protection via Enhancement of MUC5AC and MUC6 by Geranylgeranylacetone

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