Hypergastrinemia is associated with decreased gastric acid secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats

Mably, Thomas A.; Theobald, Holger; Ingall, Glynnis B.; Peterson, Richard E.

doi:10.1016/0041-008x(90)90346-v

Cited by 14 publications

(5 citation statements)

References 26 publications

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“…The association was more significant with longer duration of use and diminished after treatment was discontinued ( 70 ). Similarly, TCDD is reported to decrease gastric acid secretion by reducing secretory volume, acidity, and total acid output ( 71 ). Collectively, this suggests that prolonged treatment with TCDD may reduce systemic levels of Cbl due to decreased gastric acid secretion.…”

Section: Discussionmentioning

confidence: 99%

Dioxin-elicited decrease in cobalamin redirects propionyl-CoA metabolism to the β–oxidation-like pathway resulting in acrylyl-CoA conjugate buildup

Orlowska¹,

Fling²,

Nault³

et al. 2022

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Dioxin-elicited decrease in cobalamin redirects propionyl-CoA metabolism to the β–oxidation-like pathway resulting in acrylyl-CoA conjugate buildup

Orlowska¹,

Fling²,

Nault³

et al. 2022

Journal of Biological Chemistry

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“…The association was more significant with longer duration of use and diminished after treatment was discontinued (78). Similarly, TCDD is reported to decrease gastric acid secretion by reducing secretory volume, acidity and total acid output (79). Collectively, this suggests that prolonged treatment with TCDD may reduce systemic levels of Cbl due to decreased gastric acid secretion.…”

Section: Discussionmentioning

confidence: 99%

Dioxin-elicited decrease in cobalamin redirects hepatic propionyl-CoA metabolism to the β–oxidation-like pathway resulting in acrylyl-CoA conjugate accumulation

Orlowska

Fling

Nault

et al. 2021

Preprint

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2,3,7,8 –Tetrachlorodibenzo –p –dioxin (TCDD) is a persistent environmental contaminant and the prototypical ligand for the aryl hydrocarbon receptor (AhR). AhR mediates the effects of TCDD and related compounds, including the reprograming of intermediate metabolism. Untargeted metabolomics analysis of hepatic extracts prepared from mice orally gavaged with TCDD every 4 days for 28 days identified the dose –dependent induction of acrylyl –CoA, a highly reactive toxic intermediate produced during the metabolism of propionyl –CoA in the cobalamin (Cbl) –independent β –oxidation –like pathway. Acrylyl –CoA is a biomarker of inborn errors of metabolism associated with propionic and methylmalonic acidemia associated with Cbl deficiency, transport and/or defects in Cbl –dependent methylmalonyl –CoA mutase (MUT). Although TCDD repressed gene expression for both the canonical Cbl –dependent carboxylase and the alternate Cbl –independent β –oxidation –like pathways, inhibition occurred only at 30 μg/kg TCDD while acrylyl –CoA levels increased at ~3 μg/kg. In contrast, TCDD decreased serum Cbl and hepatic cobalt levels at ~3 μg/kg TCDD consistent with the dose –dependent increase in acrylyl –CoA levels. TCDD elicited negligible effects on the expression of genes associated with Cbl absorption, transport, trafficking and derivatization to 5 –deoxy –adenosylcobalamin (AdoCbl), the required MUT cofactor. In addition, TCDD induced the decarboxylation of cis –aconitate to itaconate by Acod1. Itaconate can then be activated to itaconyl –CoA, a MUT suicide inactivator that forms an adduct with AdoCbl, blocking MUT activity and reducing Cbl levels. Collectively, these results suggest MUT activity was impaired due to Cbl depletion by TCDD causing propionyl –CoA metabolism to be redirected to the alternate Cbl –independent β –oxidation –like pathway resulting in hepatic acrylyl –CoA accumulation.

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“…The same volume (12 ml) of 20%) sucrose solution which as an oral dose had no effect on subsequent feed intake in control rats, suppressed feed intake when given as an intragastric dose. A recent paper showed TCDD to increase serum gastrin concentration 4-fold (Mably et al 1990). Some caution is still warranted in interpreting the data from the gastric infusion experiment, since this route is more apt to elicit nausea than the oral route (Deutsch 1990).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, it might yet be worthwhile to determine the effect of meals on the secretion of the endogenous equivalents of CCK-8 and bombesin. A recent paper showed TCDD to increase serum gastrin concentration 4-fold (Mably et al 1990). The correponding releasing factor, gastrin-releasing peptide, is the mammalian counterpart of bombesin, which also has suppressive activity on feeding (Gibbs & Smith 1988).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Enhanced Responsiveness to Postingestive Satiety Signals in 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD)‐Treated Han / Wistar Rats

Pohjanvirta¹,

Unkila²,

Tuomisto³

1991

Pharmacology & Toxicology

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Previous studies have shown that under free-feeding conditions, TCDD-treated Han/Wistar (H/W) rats consume less sucrose solution but ingest more saccharin solution than their controls thus implying hyperresponsiveness to postingestive satiety signals. In this study, nutrient preloads were employed to further elucidate this phenomenon. Male H/W rats were given a single high but usually non-lethal intraperitoneal dose (1000 micrograms/kg) of TCDD. Feed intake was stimulated by 24 hr feed deprivation at various time points after TCDD exposure. When TCDD-dosed rats were allowed to drink either a 20% sucrose or a 0.25% saccharin solution and then given access to feed, those that had had sucrose ate only about 50% of the amount consumed by the saccharin group. Although the preloads were similar in control rats, no such difference in subsequent feeding occurred. The sucrose solution also produced a longer-lasting suppression of feed intake in TCDD-treated compared with control rats when infused directly into the stomach. By contrast, TCDD-treated H/W rats failed to exhibit an augmented satiety response to parenterally applied glucose independent of testing time. Oral corn oil reduced feed intake in both control and TCDD-exposed rats, but the inhibition was slightly larger in TCDD-treated animals. TCDD did not markedly affect the responsiveness of H/W rats to the suppression of feeding by CCK-8 or bombesin. It is concluded that gastrointestinal factors appear critical to the exaggerated response of TCDD-treated H/W rats to nutrient energy.

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Hypergastrinemia is associated with decreased gastric acid secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats

Cited by 14 publications

References 26 publications

Dioxin-elicited decrease in cobalamin redirects propionyl-CoA metabolism to the β–oxidation-like pathway resulting in acrylyl-CoA conjugate buildup

Dioxin-elicited decrease in cobalamin redirects propionyl-CoA metabolism to the β–oxidation-like pathway resulting in acrylyl-CoA conjugate buildup

Dioxin-elicited decrease in cobalamin redirects hepatic propionyl-CoA metabolism to the β–oxidation-like pathway resulting in acrylyl-CoA conjugate accumulation

Characterization of the Enhanced Responsiveness to Postingestive Satiety Signals in 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD)‐Treated Han / Wistar Rats

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