Alteration of rat hepatic plasma membrane functions by 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)

Matsumura, Fumio; Brewster, David; Madhukar, Burra V.; Bombick, David W.

doi:10.1007/bf01056330

Cited by 60 publications

(23 citation statements)

References 20 publications

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“…For example, TCDD can produce immunosuppression, 26) induction of protein kinases 27) and phospholipase C, 28) and effects on plasma membranes and low-density lipoprotein receptor via AhR-independent mechanisms. 29,30) Although this study failed to observe any significant effect of curucumin on AhRmediated gene expression, this substance has been reported to exhibit inhibitory effects on various signaling proteins including cyclooxygenase, ornithine decarboxylase, nitric oxide synthase, transcription factors, matrix metalloproteinases, and protein kinases. 31,32) Therefore, it may that curcumin exerts its protective effects by acting on a target(s), such as signal transduction located downstream of the AhRdependent or -independent pathways.…”

Section: Discussionmentioning

confidence: 69%

Curcumin Anticipates the Suppressed Body Weight Gain with 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Mice

Ishida

Taketoh

Nakatsune

et al. 2004

JOURNAL OF HEALTH SCIENCE

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The protective effect of curcumin, a potent inducer of heat shock protein (Hsp) 70, against the acute toxicity produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied in vivo in C57BL/6J mice. Curcumin reduced the loss of body weight gain produced by TCDD regardless of having no effect on hepatomegaly and thymic atrophy. Hsp70.1 mRNA levels in liver and intestine were unaffected or tended to be reduced by TCDD and/or curcumin treatment. Curcumin also had no effect on the induction of hepatic ethoxyresorufin O-deethylase activity by TCDD. These data suggest that curcumin exhibits a protective effect against some forms of dioxin toxicity by a mechanism(s) distinct from the increase in hepatic and intestinal Hsp70 and inhibition of arylhydrocarbon receptor activation.

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Section: Discussionmentioning

confidence: 69%

Curcumin Anticipates the Suppressed Body Weight Gain with 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Mice

Ishida

Taketoh

Nakatsune

et al. 2004

JOURNAL OF HEALTH SCIENCE

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“…TCDD was a gift from Dow and was >99% pure (GLC examined); 3,4,3',4'-tetrachloroazoxybenzene was generously given to us by M. T. Stephen Hsia (University of Wisconsin, Madison, WI) and was >99% pure; sodium phenobarbital was purchased from Mallinckrodt; 3-methylcholanthrene, and epidermal growth factor (EGF) were from Sigma; Aroclor-1242, a polychlorinated biphenyl mixture containing 42% chlorine, was a gift from Monsanto; 3,4,3',4'-tetrachlorobiphenyl (>99% pure) was obtained from Analabs, North Haven, CT; and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane >99% pure was a gift from Mon mouli et al (10) with minor modifications as described (4,5). Phosphorylation assay was done essentially as described by Rubin et al (11).…”

Section: Methodsmentioning

confidence: 99%

“…We have recently found that many plasma membrane proteins and functions of the hepatocytes from TCDD-treated rats are quantitatively different from those of untreated rats (4)(5)(6).…”

mentioning

confidence: 99%

Effects of in vivo-administered 2,3,7,8-tetrachlorodibenzo-p-dioxin on receptor binding of epidermal growth factor in the hepatic plasma membrane of rat, guinea pig, mouse, and hamster.

Madhukar¹,

Brewster²,

Matsumura³

1984

Proc. Natl. Acad. Sci. U.S.A.

133

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The effect of in vivo-administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on epidermal growth factor (EGF) receptor activity of the rat hepatic plasma membrane was studied. TCDD causes a significant reduction in EGF binding at an early stage of toxicity (day 2) and at very low doses (1 pug/kg, single i.p., rat). This reduction appears to be due to a decline in the number of receptors. There is a good correlation between levels of decline in EGF binding and loss of body weight among TCDD-treated rats. The reduction in EGF binding occurs at a relatively low dose in the guinea pig (a very sensitive species) and at high doses in the hamster (a tolerant species). Among three mice strains, TCDD (115 ptg/kg, single i.p.) caused 98% reduction in EGF binding in the sensitive strains (C57BL/6J and CBA/J) but only a 50% reduction in the tolerant strain (AKR/J). To relate the above biochemical changes to in vivo effects, TCDD was postnatally administered (through mother's milk) to mouse neonates. The most prominent toxic manifestations were early eye opening and incisor eruption, loss in body weight gain, and retardation of hair growth. All of these symptoms have been ascribed to EGF effects. TCDD was also found to stimulate phosphorylation of the EGF receptor in the rat hepatic plasma membrane. This phosphorylation effect was observed at day 1 and persisted until the end of the test (day 10). It has long been recognized that agents causing reduction in number of EGF receptors (e.g., phorbol esters) elicit in vivo cellular responses that are similar to those caused by exposure to excess doses of growth factors. Accordingly, a hypothesis has been proposed to ascribe some of the EGF-like effects of TCDD, such as fatty infiltration of the liver and hyperplastic proliferation of gastric epithelia and epidermal cells to its action on the EGF receptor. 2,3,7, is an extremely toxic compound. The oral LD50 values in the male guinea pig and the rat are cited as 0.6 ,g/kg and 22 pug/kg, respectively (1). The action pattern of TCDD is unusual in that animals treated with a single dose steadily lose weight for several weeks, until death occurs, usually in 2-8 weeks. There are marked species differences in sensitivity (2): e.g., as compared to the above species, the Golden Syrian hamster is very tolerant to TCDD; its LD50 value is cited as >5000 pug/kg. Furthermore, the toxic manifestations also qualitatively vary from species to species. The basic biochemical cause for such toxic actions of TCDD is unknown (3).We have recently found that many plasma membrane proteins and functions of the hepatocytes from TCDD-treated rats are quantitatively different from those of untreated rats (4-6).As a follow-up of such a study, the current investigation was undertaken with the following objectives: (i) find several biochemical parameters on the plasma membrane that are severely affected by TCDD, (ii) study whether any of the changes occur at low enough doses and at very early stages in susceptible species, and only at high doses in tol...

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“…4,5) However, some effects of TCDD have been shown not to require AhR; i.e., immunosuppression, 6) induction of protein kinases 7) and phospholipase C, 8) and effects on plasma membranes and low-density lipoprotein receptor. 9,10) Therefore, the exact mechanisms governing dioxin toxicity remain to be fully elucidated.…”

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confidence: 99%

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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Alteration of rat hepatic plasma membrane functions by 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)

Cited by 60 publications

References 20 publications

Curcumin Anticipates the Suppressed Body Weight Gain with 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Mice

Curcumin Anticipates the Suppressed Body Weight Gain with 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Mice

Effects of in vivo-administered 2,3,7,8-tetrachlorodibenzo-p-dioxin on receptor binding of epidermal growth factor in the hepatic plasma membrane of rat, guinea pig, mouse, and hamster.

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

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