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Oxidative stress and epigenetics in diabetic nephropathy: the potential of dietary phytochemicals

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Title
Oxidative stress and epigenetics in diabetic nephropathy: the potential of dietary phytochemicals
Name (type = personal)
NamePart (type = family)
Cheng
NamePart (type = given)
David C.
NamePart (type = date)
1990-
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David C. Cheng
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RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Kong
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Ah-Ng Tony
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Ah-Ng Tony Kong
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Advisory Committee
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chair
Name (type = personal)
NamePart (type = family)
Suh
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Nanjoo
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Nanjoo Suh
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Advisory Committee
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co-chair
Name (type = personal)
NamePart (type = family)
Androulakis
NamePart (type = given)
Ioannis
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Ioannis Androulakis
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Advisory Committee
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internal member
Name (type = personal)
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Minden
NamePart (type = given)
Audrey
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Audrey Minden
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Advisory Committee
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internal member
Name (type = personal)
NamePart (type = family)
Cai
NamePart (type = given)
Li
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Li Cai
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
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NamePart
School of Graduate Studies
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school
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Text
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theses
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2019
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2019-10
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English
Abstract (type = abstract)
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in the United States. Hyperglycemia and hemodynamic aberrations contribute to DN. But growing evidence identifies oxidative stress, inflammation, and epigenetics as playing important roles in the pathogenesis of DN. To ameliorate DN, strategies to mitigate excessive oxidative stress and inflammation or alter epigenetics have been proposed. One strategy involves the activation of Nrf2, a transcription factor that regulates the antioxidant response. Nrf2 has been discovered to play a protective role against DN and activation of Nrf2 can lower oxidative stress and inflammation in many different disease models. Development of Nrf2 activators for treating DN have been tested in clinical studies and showed promising results. However, their development has been hampered by increased adverse events. As an alternative, dietary phytochemicals have been studied as safer modalities for reducing oxidative stress and inflammation due to their antioxidant and anti-inflammatory properties. Our group has investigated the use of a novel phytochemical, MIC-1, an isothiocyanate found in Moringa oleifera, and its potential in DN. MIC-1 upregulated the Nrf2 antioxidant response in HepG2C8 cells to increase antioxidant genes in addition to reducing inflammation in RAW264.7 cells. In an in vitro HK-2 cell culture model of DN, MIC-1 reduced high glucose induced oxidative stress and reverse activation of the upstream regulator, TGFβ1, a key driver in DN development and progression. Though oxidative stress and inflammation play important roles in DN, epigenetics have also been identified to contribute to DN. One type of epigenetic modification, DNA methylation, plays an important role in gene regulation of many diseases including cancer and diabetes. Our study showed that in an in vivo model of early DN, DNA methylation alterations can influence gene expression that contribute towards driving DN progression. Evidence for use of dietary phytochemicals found commonly in over-the-counter medicines in human are limited. To assess the potential of dietary phytochemicals in humans, a small study on a single dose of oral curcumin in healthy human volunteers was performed. Parent curcumin was not detectable in subjects’ plasma. However, levels of curcumin metabolite were detected along with increases in antioxidant genes and decreases in epigenetic modifying enzymes. Collectively, dietary phytochemicals modulate antioxidant and epigenetic genes that could contribute to ameliorating DN. The long-term goal for this research is to understand the epigenetic events involved in DN and to develop safer alternatives using dietary phytochemicals such as isothiocyanates and curcumin to influence oxidative stress, inflammation, and epigenetic alterations.
Subject (authority = RUETD)
Topic
Pharmaceutical Science
Subject (authority = LCSH)
Topic
Diabetic nephropathies -- Prevention
RelatedItem (type = host)
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Rutgers University Electronic Theses and Dissertations
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ETD_10371
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application/pdf
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1 online resource (xv, 163 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
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School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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NjNbRU
Identifier (type = doi)
doi:10.7282/t3-s6th-9z64
Genre (authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Cheng
GivenName
David
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-09-30 01:01:28
AssociatedEntity
Name
David Cheng
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
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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.
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Type
Embargo
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2020-10-30
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 30th, 2020.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2019-09-30T00:58:52
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