Reduction of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice using an antiulcer drug, geranylgeranylacetone

Takumi Ishida, Tomomi Oshimo, Akihisa Nishimura, Junpei Mutoh, Yuji Ishii, Nobuyuki Koga, Hideyuki Yamada, Isao Hashiguchi, Akifumi Akamine, Kazuta Oguri

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Abstract

The protective effect of geranylgeranylacetone (GGA), an antiulcer drug, against the acute toxicity and teratogenicity produced by 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) was examined in C57BL/6J mice. When mice were co-treated, GGA reduced the loss of body weight gain and lethality produced by TCDD but hepatomegaly and thymic atrophy were not improved. Additionally, no protective effect of GGA was observed in the formation of cleft palate and hydronephrosis in mouse fetuses caused by maternal exposure to TCDD. To clarify the reducing mechanism by GGA, the Hsp70.1 mRNA levels in liver and intestine were analyzed. However, it was difficult to explain the effect of GGA from the induction of Hsp70.1. GGA had also no effect on the induction of hepatic ethoxyresorufin O-deethylase activity by TCDD. These data suggest that GGA exhibits a protective effect against some forms of dioxin toxicity by a mechanism without involving inhibition of arylhydrocarbon receptor activation.

Original languageEnglish
Pages (from-to)1397-1402
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume27
Issue number9
DOIs
Publication statusPublished - Sep 1 2004

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geranylgeranylacetone
Pharmaceutical Preparations
Maternal Exposure
Cytochrome P-450 CYP1A1
Dioxins
Hepatomegaly
Hydronephrosis
Liver
Cleft Palate
Polychlorinated Dibenzodioxins
Inbred C57BL Mouse
Weight Gain
Atrophy
Intestines

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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Reduction of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice using an antiulcer drug, geranylgeranylacetone. / Ishida, Takumi; Oshimo, Tomomi; Nishimura, Akihisa; Mutoh, Junpei; Ishii, Yuji; Koga, Nobuyuki; Yamada, Hideyuki; Hashiguchi, Isao; Akamine, Akifumi; Oguri, Kazuta.

In: Biological and Pharmaceutical Bulletin, Vol. 27, No. 9, 01.09.2004, p. 1397-1402.

Research output: Contribution to journalArticle

Ishida, Takumi ; Oshimo, Tomomi ; Nishimura, Akihisa ; Mutoh, Junpei ; Ishii, Yuji ; Koga, Nobuyuki ; Yamada, Hideyuki ; Hashiguchi, Isao ; Akamine, Akifumi ; Oguri, Kazuta. / Reduction of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice using an antiulcer drug, geranylgeranylacetone. In: Biological and Pharmaceutical Bulletin. 2004 ; Vol. 27, No. 9. pp. 1397-1402.
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