Mouse model of fetal alcohol spectrum disorders according to two human alcohol drinking patterns and the role of epigallocatechin gallate in their prevention. Epigallocatechin gallate bioavailability study in humans
[eng] HYPOTHESIS: Prenatal alcohol exposure produces different degrees of fetal growth restriction, placental disorders, and brain impairments in humans depending on the type of exposure (acute or binge versus chronic moderate or Mediterranean). EGCG therapy administered under optimal pharmacokineti...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/205392 |
| Acceso en línea: | https://hdl.handle.net/2445/205392 http://hdl.handle.net/10803/689707 |
| Access Level: | acceso abierto |
| Palabra clave: | Trastorns de l'espectre alcohòlic fetal Creixement fetal Polifenols Fetal alcohol spectrum disorders Fetal growth Polyphenols |
| Sumario: | [eng] HYPOTHESIS: Prenatal alcohol exposure produces different degrees of fetal growth restriction, placental disorders, and brain impairments in humans depending on the type of exposure (acute or binge versus chronic moderate or Mediterranean). EGCG therapy administered under optimal pharmacokinetic conditions may attenuate these abnormalities. The specific hypotheses of this doctoral thesis are: 1. Binge human-like pattern of PAE produces more severe fetal growth restriction and placental disorders than Mediterranean PAE 2. Binge human-like pattern of PAE produces more severe brain impairment in comparison to Mediterranean PAE 3. EGCG therapy administered under optimal pharmacokinetic conditions may mitigate placental and brain alterations produced by PAE according to the two human-like drinking patterns (binge versus Mediterranean) 4. Highest plasma concentrations are reached with oral EGCG administration without food supplements 5. Food supplements improve the stability of oral EGCG administration. OBJECTIVES: The main objectives of this thesis are to evaluate the protective effect of EGCG on a FASD-like mouse model exposed to two human-like drinking patterns (acute or binge versus chronic moderate or Mediterranean) and assess the specific EGCG bioavailability profile in humans under different nutritional conditions. The specific objectives of this doctoral thesis are: 1. To assess the effects of binge versus Mediterranean alcohol exposure on fetal growth and placenta, based on fetal and placental weight and placental angiogenesis biomarkers 2. To analyze the effects of binge versus Mediterranean alcohol exposure on maturation, differentiation, and plasticity in fetal brain processes based on specific neuronal biomarkers 3. To study the protective effect of EGCG on fetal growth, placental development, and neurogenesis processes 4. To analyze the bioavailability of oral EGCG administered alone or with different food supplements in healthy volunteers 5. To evaluate the pharmacokinetic parameters of EGCG in healthy volunteers. |
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