Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits

Natalia Estrada‐Ortiz; Viktoriia Starokozhko; Hidde SteenwijkCor HeideHjalmar PermentierLisanne HeemskerkGrietje Harmanna PrinsJanette HeegsmaKlaas Nico FaberSteffi BressersGuy SteiblenAntoinette GrootSteve GroomeErik MiertGeny GroothuisInge Anne Maria Graaf

首页> 外文期刊>Journal of applied toxicology >Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits

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Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits

机译：Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits

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Abstract 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.

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《Journal of applied toxicology》 |2022年第12期|1921-1936|共16页
作者
Natalia Estrada‐Ortiz; Viktoriia Starokozhko; Hidde SteenwijkCor HeideHjalmar PermentierLisanne HeemskerkGrietje Harmanna PrinsJanette HeegsmaKlaas Nico FaberSteffi BressersGuy SteiblenAntoinette GrootSteve GroomeErik MiertGeny GroothuisInge Anne Maria Graaf;
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Groningen Research Institute of Pharmacy (GRIP),University of Groningen;

Department of Gastroenterology and Hepatology, University of Groningen,University Medi‐cal Center;

Charles River LaboratoriesSolvay, Toxicological and Environmental Risk Assessment UnitUniversity Medical Center Groningen, Surgical Research Laboratory,University of GroningenSolvay, Product Stewardship;

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正文语种英语
中图分类毒物学（毒理学）;
关键词
cytochrome p45026A1; precision‐cut liver slices; retinoid binding proteins; retinoids; teratogenicity; tetrakis(hydroxymethyl) phosphonium sulphate; THPS; VAD; vitamin A homeostasis;

Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits

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