Effect of geranylgeranylacetone (GGA) on gastric lesions induced by topical aspirin plus HCl.

Murakami, Manabu; Oketani, Kiyoshi; Fujisaki, Hideaki; Wakabayashi, Tsuneo

doi:10.1254/jjp.32.921

Cited by 18 publications

(11 citation statements)

References 8 publications

(7 reference statements)

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“…TPA is a novel antiuicer drug developed in Japan [3][4][5][6], Murakami et al [3,5,6] found that TPA prevented the gastric hexosamine content from being reduced by cold restraint stress. Terano et al…”

Section: Discussionmentioning

confidence: 99%

“…Tetraprenylacetone (TPA), a novel antiulcer drug, was developed in Japan [3][4][5][6], This drug has been shown to protect the gastric mucosa in rats against noxious agents by a mechanism that does not involve the inhibition of acid secretion [7], More recent studies suggest that this agent's protective effect is related to its ability to stimulate mucus production [8].…”

mentioning

confidence: 99%

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Scanning Electron Microscopic Observations on Gastric Mucus Secretion in Rats, and the Effects of Tetraprenylacetone

1995

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Mucus secretion in the gastric mucosa of rats was studied with a scanning electron microscope. After stimulation, two types of mucus secretion were observed: exocytosis and apical expulsion. Prolonged administration of tetraprenylacetone (TPA) significantly increased the number of mucus-secreting cells in both the gastric corpus and antrum 12 h after the last administration of TPA. In the secreting cells, apical expulsion was significantly more frequent among TPA-treated than in untreated rats. TPA also significantly increased the hexosamine concentration in both gastric corpus and antrum. These findings indicate that TPA stimulates both the content and the secretion of gastric mucus, and that its secretion is chiefly through apical expulsion.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Scanning Electron Microscopic Observations on Gastric Mucus Secretion in Rats, and the Effects of Tetraprenylacetone

1995

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“…Geranylgeranylacetone (GGA) is an example of an available therapeutic drug that has been shown to induce Hsps in several systems. GGA is an isoprenoid that is used clinically for the treatment of gastritis and gastric ulcers (Murakami et al 1981(Murakami et al , 1982a. GGA induces Hsp70 in a variety of tissues, including the gastric mucosa, heart, liver, brain, and cochlea (Hirakawa et al 1996;Ooie et al 2001;Oda et al 2002;Mikuriya et al 2005;Sone et al 2005).…”

Section: Figmentioning

confidence: 99%

Hsp70 Inhibits Aminoglycoside-Induced Hair Cell Death and is Necessary for the Protective Effect of Heat Shock

Taleb

Brandon

Lee

et al. 2008

JARO

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Sensory hair cells of the inner ear are sensitive to death from aging, noise trauma, and ototoxic drugs. Ototoxic drugs include the aminoglycoside antibiotics and the antineoplastic agent cisplatin. Exposure to aminoglycosides results in hair cell death that is mediated by specific apoptotic proteins, including cJun N-terminal kinase (JNK) and caspases. Induction of heat shock proteins (Hsps) is a highly conserved stress response that can inhibit JNK-and caspasedependent apoptosis in a variety of systems. We have previously shown that heat shock results in a robust upregulation of Hsps in the hair cells of the adult mouse utricle in vitro. In addition, heat shock results in significant inhibition of both cisplatin-and aminoglycoside-induced hair cell death. In our system, Hsp70 is the most strongly induced Hsp, which is upregulated over 250-fold at the level of mRNA 2 h after heat shock. Therefore, we have begun to examine the role of Hsp70 in mediating the protective effect of heat shock. To determine whether Hsp70 is necessary for the protective effect of heat shock against aminoglycoside-induced hair cell death, we utilized utricles from Hsp70.1/3 −/− mice. While heat shock inhibited gentamicin-induced hair cell death in wild-type utricles, utricles from Hsp70.1/3 −/− mice were not protected. In addition, we have examined the role of the major heat shock transcription factor, Hsf1, in mediating the protective effect of heat shock. Utricles from Hsf1 −/− mice and wild-type littermates were exposed to heat shock followed by gentamicin. The protective effect of heat shock on aminoglycoside-induced hair cell death was only observed in wildtype mice and not in Hsf1 −/− mice. To determine whether Hsp70 is sufficient to protect hair cells, we have utilized transgenic mice that constitutively overexpress Hsp70. Utricles from Hsp70-overexpressing mice and wild-type littermates were cultured in the presence of varying neomycin concentrations for 24 h. The Hsp70-overexpressing utricles were significantly protected against neomycin-induced hair cell death at moderate to high doses of neomycin. This protective effect was achieved without a heat shock. Taken together, these data indicate that Hsp70 and Hsf1 are each necessary for the protective effect of heat shock against aminoglycoside-induced death. Furthermore, overexpression of Hsp70 alone significantly inhibits aminoglycoside-induced hair cell death.

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“…Tetraprenylacetone (TPA) protects the gastric mucosa against noxious agents such as aspirin [ 1 ], aspirin plus HC1 [2], and abso lute ethanol [3] in rats by a mechanism that does not involve the inhibition of acid secre tion. However, whether TPA can protect the human gastric mucosa against noxious agents is not known.…”

Section: Introductionmentioning

confidence: 99%

Gastric Cytoprotection by Tetraprenylacetone in Human Subjects

Yamada¹,

Nakamura²,

Nebiki³

et al. 1988

Digestion

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We assessed the inhibition by tetraprenylacetone (TPA) of gastric mucosal damage caused by ethanol in human subjects. Seventeen healthy volunteers were given either TPA (a 50-mg capsule) or a placebo 3 times daily for 5 days. Then, 20 ml of 70% ethanol were sprayed onto the gastric antrum and 15 min later, visible mucosal lesions were evaluated with an endoscope, and biopsy specimens were taken from mucosa that looked normal but had been sprayed with ethanol. The specimens were observed by light microscopy and scanning electron microscopy. The gross mucosal damage was significantly less (p < 0.05) in the subjects given TPA than in those given the placebo. Hyperemia and hemorrhage in the mucosa and surface epithelial damage were also significantly less (p < 0.05) in the subjects given TPA. The results suggested that TPA protects the gastric mucosa from damage by ethanol as judged not only by the gross appearance of the mucosa but also by microscopic observation.

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Effect of geranylgeranylacetone (GGA) on gastric lesions induced by topical aspirin plus HCl.

Cited by 18 publications

References 8 publications

Scanning Electron Microscopic Observations on Gastric Mucus Secretion in Rats, and the Effects of Tetraprenylacetone

Scanning Electron Microscopic Observations on Gastric Mucus Secretion in Rats, and the Effects of Tetraprenylacetone

Hsp70 Inhibits Aminoglycoside-Induced Hair Cell Death and is Necessary for the Protective Effect of Heat Shock

Gastric Cytoprotection by Tetraprenylacetone in Human Subjects

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