260 Pages
English

Impact of folate absorption and transport for nutrition and drug targeting [Elektronische Ressource] / N. Ceren Alemdaroglu

-

Gain access to the library to view online
Learn more

Description

Impact of Folate Absorption and Transport for Nutrition and Drug Targeting Dissertation zur Erlangung des Grades “Doktor der Naturwissenchaften” am Fachbereich Chemie, Pharmazie und Geowissenschaften der Johannes Gutenberg-Universität Mainz N. Ceren Alemdaroglu geb. in Ankara Mainz 2007 ii Dedicated to my husband, Fikri… v viTABLE OF CONTENTS Acknowledgements………………………………………………………………......vii Table of contents……………………………………………………………………..ix List of abbreviations…………………………………………………………………xi Chapter 1…...Chemistry, biochemical role, absorption and significance of folic acid & general aspects of flavonoids…….…………………...1 Objectives……………………………………………………………35 References……………………………………………………………37 Chapter 2…..In vitro cell culture studies, drug- and nutrient- interactions of folic acid ………………………....................................................51 Chapter 2.1…In vitro cell culture model for studying folic acid interactions……...53 Chapter 2.2…Expression of folate transport routes in Caco-2 cells: Reverse transcription PCR (RT-PCR) and real-time PCR……………………79 Chapter 2.3…Effect of green tea catechins and tea extracts on folic acid uptake….90 Chapter 2.

Subjects

Informations

Published by
Published 01 January 2007
Reads 13
Language English
Document size 2 MB

Impact of Folate Absorption and Transport for
Nutrition and Drug Targeting



Dissertation
zur Erlangung des Grades
“Doktor der Naturwissenchaften”


am Fachbereich
Chemie, Pharmazie und Geowissenschaften
der Johannes Gutenberg-Universität Mainz






N. Ceren Alemdaroglu
geb. in Ankara



Mainz 2007




































ii

















Dedicated to my husband, Fikri…














v
































viTABLE OF CONTENTS

Acknowledgements………………………………………………………………......vii
Table of contents……………………………………………………………………..ix
List of abbreviations…………………………………………………………………xi
Chapter 1…...Chemistry, biochemical role, absorption and significance
of folic acid & general aspects of flavonoids…….…………………...1
Objectives……………………………………………………………35
References……………………………………………………………37
Chapter 2…..In vitro cell culture studies, drug- and nutrient- interactions
of folic acid ………………………....................................................51
Chapter 2.1…In vitro cell culture model for studying folic acid interactions……...53
Chapter 2.2…Expression of folate transport routes in Caco-2 cells: Reverse
transcription PCR (RT-PCR) and real-time PCR……………………79
Chapter 2.3…Effect of green tea catechins and tea extracts on folic acid uptake….90
Chapter 2.4…Investigation of the interaction between folic acid and selected
flavonoids at the level of intestinal absorption……………………...106
Chapter 2.5…Investigation of the interaction between folic acid and
antiepileptics at the level of intestinal absorption………………….. 114
Chapter 2.6…In vitro toxicology assays………………………………………….. 121
Chapter 2.7…Scintillation counting………………………………………………. 124
References………………………………………………………….. 126
Chapter 3…...Influence of green and black tea on folic acid
Pharmacokinetics in healthy volunteers: A potential risk of
diminished folic acid bioavailability……………………….……….137
ixReferences…………………………………………………………..161
Chapter 4…..Targeting of DNA block copolymer micelles to folate
receptors: A new system for selective drug delivery to FR α
expressing cancer cells …………………..........................................167
References…………………………………………………………..184
Chapter 5…...Summary............................................................................................191
Zusammenfassung…………………………………………………..194
Curriculum Vitae……………………………………………………197
Chapter 6…...Appendix……………………………………………………………199





















xLIST OF ABBREVIATIONS

10-FTHF 10-Formyltetrahydrofolate
5,10-MeTHF 5,10-Methylenetetrahydrofolate
5-FTHF 5-Form
5-MTHF 5-Methyltetrahydrofolate
ABC ATP-binding cassette
ATCC American Type Culture Collection
BCRP Breast cancer resistance protein
BSA Bovine serum albumin
CLSM Confocal laser scanning microscopy
CV Coefficient of variation
CYP Cytochrome P450
DFE Dietary Folate Equivalent
DHF Dihydrofolate
DHFR reductase
DLS Dynamic light scattering
DMSO Dimethyl sulfoxide
DSMZ Deutsche Sammlung von Mikroorganismen und Zellkulturen
EC (-)-Epicatechin
ECG techin-3-gallate
EGC (-)-Epigallocatechin
EGCG (-)-Epigallocatechin-3-gallate
ESI-MS Electrospray ionization-mass spectrometry
FDA Food and Drug Administration
FPGS Folylpolyglutamate synthetase
FR Folate receptor
GAPDH Glyceraldehyde-3-phosphate dehydrogenase
HBSS Hank`s buffered salt solution
HEPES 2-[4-(2-Hydroxyethyl)-1-piperazinyl]-ethanesulfonic acid
K Michaelis-Menten constant m
IECs Intestinal epithelial cells
MCT Monocarboxylate transporter
xiMDR Multidrug resistance
MES 2-Morpholinoethanesulfonic acid monohydrate
MRP rug resistance protein
MTHFR Methylenetetrahydrofolate reductase
MTX Methotrexate
NHS N-hydroxysuccinimide
NTDs Neural tube defects
OATP Organic anion transporting polypeptides
OD Optical density
ODN Oligodeoxynucleotide
PAGE Polyacrylamide gel electrophoresis
PBS Phosphate buffered saline
PCFT Proton-coupled folate transporter
PCR Polymerase chain reaction
P Effective permeability coefficient eff
Pgp P-glycoprotein
pK Dissociation constant a
PPO Poly(propylene oxide)
RDA Recommended dietary allowance
RFC Reduced folate carrier
RT-PCR Reverse transcription PCR
SGLT1 Sodium-dependent glucose transporter
SLC Solute carrier
TEER Transepithelial electrical resistance
THF Tetrahydrofolate




xii

CHAPTER ONE








CHEMISTRY, BIOCHEMICAL ROLE, ABSORPTION AND
SIGNIFICANCE OF FOLIC ACID
&
GENERAL ASPECTS OF FLAVONOIDS



















CHAPTER 1

































2