RUcore: Rutgers University Community Repository
Synergestic induction of NRF-2 gene by curcumin and sulforaphane and pharmacokinetics/metabolism of 13C/Dim in rats by UPLC/MS
Descriptive
TypeOfResource
Text
TitleInfo
(ID = T-1)
Title
Synergestic induction of NRF-2 gene by curcumin and sulforaphane and pharmacokinetics/metabolism of 13C/Dim in rats by UPLC/MS
TitleInfo
(ID = T-2);
(type = alternative)
Title
Pharmacokinetics and pharmacodynamics of dietary cancer chemopreventive phytochemicals
Identifier
ETD_3115
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000057585
Language
LanguageTerm
(authority = ISO639-2);
(type = code)
eng
Genre
(authority = marcgt)
theses
Subject
(ID = SBJ-1);
(authority = RUETD)
Topic
Pharmaceutical Science
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
Cancer--Chemoprevention
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Cancer--Treatment
Subject
(ID = SBJ-4);
(authority = ETD-LCSH)
Topic
Carcinogenesis
Subject
(ID = SBJ-5);
(authority = ETD-LCSH)
Topic
Phytochemicals
Abstract
(type = abstract)
Curcumin (CUR) and Sulforaphane (SFN) have shown remarkable cancer chemopreventive effects in numerous studies and combinations of low doses of chemopreventive agents can reduce toxicity while augmenting efficacy. The first part of the thesis investigated the chemotherapeutic effects elicited by a combination of CUR and SFN on human hepatocarcinoma
cells. The combination treatment- mediated effects on phase II/antioxidant enzymatic induction and antioxidant response element (ARE) was investigated. It was proposed that the combination of CUR and SFN could synergistically enhance the induction of ARE and the nuclear E2-factor related factor 2 (Nrf2)-mediated enzymes. Low doses of CUR and SFN significantly induced the expression of Nrf2-mediated enzymes, HO-1 and UGT1A1, promoted nuclear translocation of
Nrf2– a key regulator of phase II detoxifying /antioxidant enzymes – and synergistically induced the ARE luciferase activity. Chemical inhibitors of mRNA and protein synthesis affected the combination therapy- mediated transcriptional regulation of both HO-1 and UGT1A1. Synergism of CUR and SFN was evident at low concentrations. Such synergism in ARE-luciferase activity may partly explain the significant induction in the expression of Nrf2- mediated expression of HO-1 and UGT1A1 and the nuclear translocation of Nrf2, suggesting that a combination of low doses may be a promising strategy for cancer chemoprevention. For the second part of this thesis, a liquid chromatographic method was validated for the simultaneous analysis and pharmacokinetic evaluation of Indole-3-Carbinol (I3C), Diindolylmethane (DIM), and several I3C metabolites. I3C and DIM are naturally derived phytochemicals with promising in-vitro and
in-vivo anticarcinogenic properties. Using reversed-phase ultra performance liquid
chromatography (UPLC) coupled with mass spectrophotometry (MS), a rapid, specific, and high
throughput method was developed and validated for the quantification and identification of I3C, DIM, and other I3C metabolites in plasma. Recovery, linearity, precision, accuracy, and stability analysis fulfilled the CDER guidelines criteria. The method was successfully applied to the determination of the pharmacokinetic parameters and elucidation of metabolites of I3C or DIM
after oral, intravenous, or intraperitoneal administration to Sprague- Dawley rats.
cells. The combination treatment- mediated effects on phase II/antioxidant enzymatic induction and antioxidant response element (ARE) was investigated. It was proposed that the combination of CUR and SFN could synergistically enhance the induction of ARE and the nuclear E2-factor related factor 2 (Nrf2)-mediated enzymes. Low doses of CUR and SFN significantly induced the expression of Nrf2-mediated enzymes, HO-1 and UGT1A1, promoted nuclear translocation of
Nrf2– a key regulator of phase II detoxifying /antioxidant enzymes – and synergistically induced the ARE luciferase activity. Chemical inhibitors of mRNA and protein synthesis affected the combination therapy- mediated transcriptional regulation of both HO-1 and UGT1A1. Synergism of CUR and SFN was evident at low concentrations. Such synergism in ARE-luciferase activity may partly explain the significant induction in the expression of Nrf2- mediated expression of HO-1 and UGT1A1 and the nuclear translocation of Nrf2, suggesting that a combination of low doses may be a promising strategy for cancer chemoprevention. For the second part of this thesis, a liquid chromatographic method was validated for the simultaneous analysis and pharmacokinetic evaluation of Indole-3-Carbinol (I3C), Diindolylmethane (DIM), and several I3C metabolites. I3C and DIM are naturally derived phytochemicals with promising in-vitro and
in-vivo anticarcinogenic properties. Using reversed-phase ultra performance liquid
chromatography (UPLC) coupled with mass spectrophotometry (MS), a rapid, specific, and high
throughput method was developed and validated for the quantification and identification of I3C, DIM, and other I3C metabolites in plasma. Recovery, linearity, precision, accuracy, and stability analysis fulfilled the CDER guidelines criteria. The method was successfully applied to the determination of the pharmacokinetic parameters and elucidation of metabolites of I3C or DIM
after oral, intravenous, or intraperitoneal administration to Sprague- Dawley rats.
PhysicalDescription
Form
(authority = gmd)
electronic resource
Extent
x, 91 p. : ill.
InternetMediaType
application/pdf
InternetMediaType
text/xml
Note
(type = degree)
M.S.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Yury Y. Gomez
Name
(ID = NAME-1);
(type = personal)
NamePart
(type = family)
Gomez
NamePart
(type = given)
Yury Y.
NamePart
(type = date)
1982-
Role
RoleTerm
(authority = RULIB)
author
DisplayForm
Yury Gomez
Name
(ID = NAME-2);
(type = personal)
NamePart
(type = family)
KONG
NamePart
(type = given)
AH-NG
Role
RoleTerm
(authority = RULIB)
chair
Affiliation
Advisory Committee
DisplayForm
AH-NG KONG
Name
(ID = NAME-3);
(type = personal)
NamePart
(type = family)
Minko
NamePart
(type = given)
Tamara
Role
RoleTerm
(authority = RULIB)
internal member
Affiliation
Advisory Committee
DisplayForm
Tamara Minko
Name
(ID = NAME-4);
(type = personal)
NamePart
(type = family)
Michniak
NamePart
(type = given)
Bonzena
Role
RoleTerm
(authority = RULIB)
internal member
Affiliation
Advisory Committee
DisplayForm
Bonzena Michniak
Name
(ID = NAME-1);
(type = corporate)
NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
(ID = NAME-2);
(type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm
(authority = RULIB)
school
OriginInfo
DateCreated
(qualifier = exact)
2011
DateOther
(qualifier = exact);
(type = degree)
2011-01
Place
PlaceTerm
(type = code)
xx
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
(type = local)
rucore19991600001
Location
PhysicalLocation
(authority = marcorg);
(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T39W0F5G
Genre
(authority = ExL-Esploro)
ETD graduate
Back to the top
Rights
RightsDeclaration
(AUTHORITY = GS);
(ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder
(ID = PRH-1);
(type = personal)
Name
FamilyName
Gomez
GivenName
Yury
Role
Copyright Holder
RightsEvent
(ID = RE-1);
(AUTHORITY = rulib)
Type
Permission or license
DateTime
2011-01-04 17:04:04
AssociatedEntity
(ID = AE-1);
(AUTHORITY = rulib)
Role
Copyright holder
Name
Yury Gomez
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
(ID = AO-1);
(AUTHORITY = rulib)
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
(ID = RE-2);
(AUTHORITY = rulib)
Type
Embargo
DateTime
2011-01-31
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after January 31st, 2012.
Back to the top
Technical
ContentModel
ETD
MimeType
(TYPE = file)
application/pdf
MimeType
(TYPE = container)
application/x-tar
FileSize
(UNIT = bytes)
1413120
Checksum
(METHOD = SHA1)
1f173d9bba2d6b67bed01ab3929e32d5305e916d
Back to the top
Statistical Profile