Reduction of the Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Mice Using an Antiulcer Drug, Geranylgeranylacetone

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.

Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice

“…Thus, GGA pretreatment quickly and transiently elevated the expression of HSP70 protein in eyes. These results are consistent with a previous study examining other organs (Ishida et al, 2004).…”

The Plant Flavonoid, Quercetin, Reduces Some Forms of Dioxin Toxicity by Mechanism Distinct from Aryl Hydrocarbon Receptor Activation, Heat-Shock Protein Induction and Quenching Oxidative Stress

“…In general, while the expression of Hsps is very low under normal physiological conditions, 22) those proteins are induced by various stresses such as stimuli by xenochemicals. 23) Although we previously reported the induction of hepatic Hsp70 by dioxins, 4,5) one of our previous studies performed with the same dose and schedule of TCDD administration as the present study also failed to show any notable TCDD-dependent increase in Hsp70.1 mRNA.…”

“…This is partially supported by our previous observation that geranylgeranylacetone and curcumin, potent inducers of Hsp70, significantly attenuated the reduction in body weight gain and lethality in C57BL/6J mice produced by TCDD. 5,6) Flavonoids are thought to improve health, and this effect seems to be due at least partially to their antioxidant effects. Diets rich in phenolic flavonoids such as quercetin reduce the risk of chronic degen- To clarify the relationship between heat shock protein (Hsp) 70 expression and dioxin toxicity, we studied the effect of quercetin, which is an inhibitor of the biosynthesis of Hsp70, on the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6J mice.…”

Developmental exposure of mice to TCDD elicits a similar uterine phenotype in adult animals as observed in women with endometriosis

“…The studies presented herein examined the impact of a relatively high dose (10 μg/kg) of TCDD compared to human background levels. However, the dose of TCDD used in the present study was similar to that reported by other investigators [56][57][58] and was chosen to insure that we could identify appropriate endpoints in offspring animals. Importantly, humans are exposed to complex mixtures of toxicants which are collectively capable of interacting with the AhR [59].…”