Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57B16 mice

Vos, J.G.; Moore, J. A.; Zinkl, Joseph G.

doi:10.1016/0041-008x(74)90060-x

Cited by 154 publications

(46 citation statements)

References 14 publications

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“…As has been reported already, the minimum dose of TCDD required to produce toxicity differs depending on the particular toxic effect; for example, in C57BL mice, loss of body weight gain, over 95 mg/kg 21) ; LD 50 , 114 mg/kg 27) ; hepatomegary and thymic atrophy, 1 mg/kg 27) ; and cleft palate and kidney malformation, 3 mg/kg. 28) Therefore, each toxic sign has a different threshold.…”

Section: Discussionmentioning

confidence: 97%

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

Ishida

Oshimo

Nishimura

et al. 2004

Biological & Pharmaceutical Bulletin

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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.

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Section: Discussionmentioning

confidence: 97%

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

Ishida

Oshimo

Nishimura

et al. 2004

Biological & Pharmaceutical Bulletin

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“…Alternatively, the reduction in fibrosis may be coupled to the observed reduction in bile duct proliferation in PAR-1-deficient mice. TCDD exposure was previously reported to cause bile duct proliferation (Vos et al, 1974), although the mechanism remains elusive.…”

Section: Discussionmentioning

confidence: 99%

From the Cover: Coagulation-Driven Hepatic Fibrosis Requires Protease Activated Receptor-1 (PAR-1) in a Mouse Model of TCDD-Elicited Steatohepatitis

et al. 2016

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Emerging evidence supports a role for environmental chemical exposure in the pathology of non-alcoholic fatty liver disease (NAFLD), a disease process tightly linked to increased activity of the blood coagulation cascade. Exposure of C57BL/6 mice to the persistent environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) recapitulates features of the NAFLD spectrum, including steatosis, hepatic injury, inflammation, and fibrosis. We assessed coagulation cascade activation, and determined the role of the thrombin receptor protease activated receptor-1 (PAR-1) in experimental TCDDelicited NAFLD. Chronic exposure to TCDD (30 mg/kg every 4 days for 28 days) was associated with intrahepatic coagulation, indicated by increased plasma thrombin-antithrombin levels and hepatic fibrin(ogen) deposition. PAR-1 deficiency diminished TCDD-elicited body weight loss and relative liver weight was reduced in TCDD-exposed PAR-1 À/À mice compared with TCDD-exposed wild-type mice. PAR-1 deficiency did not affect TCDD-induced hepatic steatosis or hepatocellular injury, as indicated by serum alanine aminotransferase activity. Despite a lack of effect on these 2 features of NAFLD pathology, PAR-1 deficiency was associated with a reduction in hepatic inflammation evident in liver histopathology, and reflected by a reduction in serum levels of the proinflammatory cytokine interleukin-6. Moreover, TCDD-driven hepatic collagen deposition was markedly reduced in PAR-1-deficient mice. These results indicate that experimental TCDD-elicited steatohepatitis is associated with coagulation cascade activation and PAR-1-driven hepatic inflammation and fibrosis.

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“…Vos et al (140) found the most significant findings in both mice and guinea pigs treated with sublethal doses of TCDD were in the lymphoid system where there was a supression of cell mediated immunity at doses of 2 and 5 pg/kg TCDD.…”

Section: B the Subacute And Chronic Toxicity Potentials Of Tcddmentioning

confidence: 99%

“…The main target organs of TCDD in rats, guinea pigs and mice appeared to be the liver and thymus (56,69,70,139,140). The degree of hepatic involvement appeared to be dose dependent and the severity of the changes produced varied between species (56).…”

Section: B the Subacute And Chronic Toxicity Potentials Of Tcddmentioning

confidence: 99%

The Toxicology, Environmental Fate, and Human Risk of Herbicide Orange and Its Associated Dioxin

Young¹,

Calcagni²,

Thalken³

et al. 1978

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Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57B16 mice

Cited by 154 publications

References 14 publications

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

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

From the Cover: Coagulation-Driven Hepatic Fibrosis Requires Protease Activated Receptor-1 (PAR-1) in a Mouse Model of TCDD-Elicited Steatohepatitis

The Toxicology, Environmental Fate, and Human Risk of Herbicide Orange and Its Associated Dioxin

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