Reduction of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice using an antiulcer drug, geranylgeranylacetone.
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.
Ishida
Takumi
T
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Oshimo
Tomomi
T
Nishimura
Akihisa
A
Mutoh
Junpei
J
Ishii
Yuji
Y
Koga
Nobuyuki
N
Yamada
Hideyuki
H
Hashiguchi
Isao
I
Akamine
Akifumi
A
Oguri
Kazuta
K
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000502:physiology; D007668:Kidney / Q000002:abnormalities; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011247:Pregnancy; D013997:Time Factors
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D000072317:Polychlorinated Dibenzodioxins; C031049:geranylgeranylacetone