Fetal Death from Nicotinamide-Deficient Diet and Its Prevention by Chlorpromazine and Imipramine

Fratta, Italo; Zak, Sylvia B.; Greengard, Paul; Sigg, E.B.

doi:10.1126/science.145.3639.1429

Cited by 15 publications

(4 citation statements)

References 12 publications

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“…Because nicotinic acid is a precursor of NAD + , 51 the significant decrease in nicotinic acid levels that we observed was likely due to DEHP exposure. Also, Fratta et al 52 demonstrated that niacin including nicotinic acid is essential for fetal growth; thus, the decrease in nicotinic acid levels upon DEHP exposure was related to fetal growth in our study. Fukuwatari et al 53 reported that DEHP enhances the bioconversion of tryptophan to nicotinamide (niacinamide) in male rats via the inhibition of α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase though there was no description on nicotinic acid.…”

Section: Discussionsupporting

confidence: 70%

Metabolomics and Data-Driven Bioinformatics Revealed Key Maternal Metabolites Related to Fetal Lethality via Di(2-ethylhexyl)phthalate Exposure in Pregnant Mice

et al. 2022

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We performed serum metabolome analysis of di(2-ethylhexyl)phthalate (DEHP)-exposed and control pregnant mice. Pregnant mice ( n = 5) were fed a DEHP-containing diet (0.1% or 0.2% DEHP) or a normal diet (control) from gestational days 0–18. After maternal exposure to 0.2% DEHP there were no surviving fetuses, indicating its strong fetal lethality. There were no significant differences in the numbers of fetuses and placentas between the 0.1% DEHP and control groups, although fetal viability differed significantly between them, suggesting that maternal exposure to 0.1% DEHP could inhibit fetal growth. Metabolomics successfully detected 169 metabolites in serum. Principal component analysis (PCA) demonstrated that the three groups were clearly separated on PCA score plots. The biological interpretation of PC1 was fetal lethality, whereas PC2 meant metabolic alteration of pregnant mice via DEHP exposure without fetal lethality. In particular, the first component was significantly correlated with fetal viability, demonstrating that maternal metabolome changes via DEHP exposure were strongly related to fetal lethality. Levels of some amino acids were significantly increased in the DEHP-exposed groups, whereas those of some fatty acids, nicotinic acid, and 1,5-anhydroglucitol were significantly decreased in the DEHP groups. DEHP-induced increases in glycine levels could cause fetal neurological disorders, and decreases in nicotinic acid could inhibit fetal growth. In addition, a machine-learning Random forest could determine 16 potential biomarkers of DEHP exposure, and data-driven network analysis revealed that nicotinic acid was the most influential hub metabolite in the metabolic network. These findings will be useful for understanding the effects of DEHP on the maternal metabolome in pregnancy and their relationship to fetal lethality.

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Section: Discussionsupporting

confidence: 70%

Metabolomics and Data-Driven Bioinformatics Revealed Key Maternal Metabolites Related to Fetal Lethality via Di(2-ethylhexyl)phthalate Exposure in Pregnant Mice

et al. 2022

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“…Experimental diets were based on casein-starch as follows: 20% casein, 0.24% vitamin mixture [18], 4% salt mixture [24], 5% hydrogenated vegetable oil, 2%…”

Section: Methodsmentioning

confidence: 99%

Metabolism of hydrogenated palatinose, an equimolar mixture ofα-D-glucopyranosido-1,6-sorbitol andα-D-glucopyranosido-1,6-mannitol

Grupp

Siebert

1978

Res. Exp. Med.

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Hydrogenated palatinose, an equimolar mixture of alpha-D-glucopyranosido-1,6-sorbitol and alpha-D-glucopyranosido-1,6-mannitol, was investigated as a potential oral sugar substitute in the following experiments in man and rat. 1. Enzymatic cleavage occurred at slow rates by maltase (alpha-glucosidase) of jejunal mucosa, liver lysosomes and yeast. 2. Part of ingested hydrogenated palatinose arrived unsplit at the caecum of the rat and underwent fermentation there; excretion in feces and urine are neglegible in man and rat. 3. Growth and maintenance of rats demonstrated 20--40 percent diminished caloric utilisation of diets containing 34.5 percent hydrogenated palatinose whereas indirect calorimetry in man showed about 50 percent caloric deficit. 4. Blood sugar did not increase in man after oral doses up to 100 g. 5. The capacity of the rat kidneys for excretion of hydrogenated palatinose and its constituents was high, symptoms of incompatibility were not observed.

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“…O n the other hand, a substance that in itself could act as a teratogen under certain circumstances can protect embryos against another teratogen. Fratta et al (1964), for instance, demonstrated a protective effect of chlorpromazine on teratogenesis obtained by nicotinamid deficiency, whereas, for instance, Brock & Kreybig ( 1964), showed a teratogenic effect of chlorpromazine on rats. Immobilization of the pregnant female increases the teratogenic effect of salicylate (Goldman et al 1963(Goldman et al , 1964 but this potentiation is prevented by chlorpromazine.…”

Section: Principles In Drug Teratogenesismentioning

confidence: 98%

Malformations Due to Toxic Influences

Källén

1968

Acta Ophthalmologica

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Fetal Death from Nicotinamide-Deficient Diet and Its Prevention by Chlorpromazine and Imipramine

Cited by 15 publications

References 12 publications

Metabolomics and Data-Driven Bioinformatics Revealed Key Maternal Metabolites Related to Fetal Lethality via Di(2-ethylhexyl)phthalate Exposure in Pregnant Mice

Metabolomics and Data-Driven Bioinformatics Revealed Key Maternal Metabolites Related to Fetal Lethality via Di(2-ethylhexyl)phthalate Exposure in Pregnant Mice

Metabolism of hydrogenated palatinose, an equimolar mixture ofα-D-glucopyranosido-1,6-sorbitol andα-D-glucopyranosido-1,6-mannitol

Malformations Due to Toxic Influences

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