التفاصيل البيبلوغرافية
| العنوان: |
Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits. |
| المؤلفون: |
Estrada‐Ortiz, Natalia, Starokozhko, Viktoriia, van Steenwijk, Hidde, van der Heide, Cor, Permentier, Hjalmar, van Heemskerk, Lisanne, Prins, Grietje Harmanna, Heegsma, Janette, Faber, Klaas Nico, Bressers, Steffi, Steiblen, Guy, de Groot, Antoinette, Groome, Steve, van Miert, Erik, Groothuis, Geny, de Graaf, Inge Anne Maria |
| المصدر: |
Journal of Applied Toxicology; Dec2022, Vol. 42 Issue 12, p1921-1936, 16p |
| مصطلحات موضوعية: |
VITAMIN A, HYDROXYMETHYL compounds, HOMEOSTASIS, VITAMINS, RABBITS, FOOD consumption, SULFATES |
| مستخلص: |
The biocide tetrakis(hydroxymethyl)phosphonium sulphate (THPS) and other members of the tetrakis(hydroxymethyl) phosphonium salts (THPX) family are associated with liver toxicity in several mammalian species and teratogenicity in rabbits. Malformations include skeletal changes and abnormalities in eye development and are very similar to those seen with vitamin A deficiency or excess. For this reason, it was hypothesized that teratogenicity of THPS(X) might be attributed to disturbances in retinol availability and/or metabolism as a result of maternal toxicity, for example, either due to insufficient dietary intake by the mothers or due to liver toxicity. Therefore, in the present study, liver toxicity and vitamin A homeostasis were studied in pregnant rabbits that were exposed to 13.8 or 46.0 mg/kg THPS during organogenesis and in precision‐cut liver slices of rats and rabbits exposed to 0–70 μM THPS. Results show that in vivo exposure to THPS leads to a marked reduction of food intake, increased plasma concentrations of γ‐glutamytransferase, degenerative changes in the liver and to changes in retinoid content in liver and plasma in the rabbits during organogenesis. In addition, THPS, both in vivo and ex vivo, caused a change in expression of proteins related to vitamin A metabolism and transport. Together, these observations could explain the birth defects observed in earlier teratogenicity studies. Pregnant rabbits and liver slices of rats and rabbits were exposed to tetrakis(hydroxymethyl)phosphonium sulphate (THPS) to investigate its interaction with vitamin A homeostasis. In the rabbits, this resulted in substantial reduction of food intake, adverse liver effects, and reduced retinol concentrations in liver and plasma. In vivo and in liver slices, THPS changed the expression of proteins related to retinoid metabolism and transport. The interference with vitamin A homeostasis could act in synergy with food deprivation leading to birth defects in rabbits following THPS exposure. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |