Regulation of cytochrome P450 2A6 and phase II enzymes by unsaturated aldehydes
- UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
- Todd Steven Mack (Creator)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
- Advisor
- Gregory Raner
Abstract: Human Phase I and Phase II drug metabolizing enzymes are known to interact
with foreign chemicals that enter the body as a defense mechanism, however, it is often
the case that unwanted interactions can occur. Phase I metabolism may form reactive
electrophiles that can covalently modify DNA, proteins and lipids. These modified
electrophilic biomolecules are thought to cause progression of many diseases such as
Parkinson’s and Alzheimer’s Disease (3). On the other hand, Phase II enzymes can
remove the toxic compounds of the Phase I enzymes. The Phase II enzymes are likely
induced via biochemical pathway involving the nuclear transcription factor Nrf2 (4).
This current study was designed to probe specific interactions between commonly
used essential oils, along with their major aldehyde constituents, and CYP2A6. The
overall goal was to gain a better understanding of factors that may govern the inhibitory
effects of aldehydes on this isoform. In addition, the ability of the essential oil of Cassia
and it’s primary constituent, cinnamaldehyde on Phase II gene induction was probed as
well using cultured human hepatoma cells (HepG2). Here the goal was to gain a better
understanding of the relationship between oxidative stress, and aldehydes that may be
present in commonly used products. The results demonstrated that relatively small
unsaturated aldehydes (6-8 carbons) showed a dramatic decrease in the CYP2A6 activity
when catalyzing the coumarin 7-hydroxylation reaction. This inhibition could translate to
a net antioxidant effect, by preventing the formation of reactive oxygen species (ROS),
particularly in the presence of 2A6-activated nitrosamines, which can be carcinogenic. It
was also shown that Cassia and cinnamaldehyde had an inductive effect on Phase II
enzymes in human hepatoma cells, such as heme oxygenase 1 (HO1) and epoxide
hydrolase (EPHX), thus exerting a net anti-oxidant effect on the cells as a whole.
Regulation of cytochrome P450 2A6 and phase II enzymes by unsaturated aldehydes
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Created on 8/1/2009
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Additional Information
- Publication
- Thesis
- Language: English
- Date: 2009
- Keywords
- Aldehydes, Cassia, Cinnamaldehyde, Hepatoma cells
- Subjects
- Enzymes $x Metabolism.
- Aldehydes.
- Cytochrome P-450.
- Antioxidants.
- Oxygenases.
- Essences and essential oils $x Physiological aspects.