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6th Internet World Congress for Biomedical Sciences

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Invited Symposium: The Therapeutic Potential of Phase II Enzyme Induction (4 Presentations in this Symposium)

Antioxidant regulation of genes encoding enzymes that detoxify xenobiotics and carcinogens.

S. Dhakshinamoorthy(1), D. Bloom(2), Anil Jaiswal(3)
(1)(2)Department of Pharmacology. Baylor College of Medicine. - Houston. United States
(3)Baylor College of Medicine - Houston. United States

[ABSTRACT] [Antioxidants and their Mode of Action] [Induction of Genes Encoding Enzymes that Detoxify Xenobiotics and Carcinogens.] [Antioxidant Response Element] [Figures] [Figures-2] [Antioxidant Response Element-Binding Proteins] [Summary and Conclusions] [Acknowledgements] [References] [Discussion Board]
ABSTRACT Previous: Phase II Enzyme Symposium Introduction Induction of Genes Encoding Enzymes that Detoxify Xenobiotics and Carcinogens.
Next: Glutathione deficiencies exacerbate response to stroke.

Antioxidants and their Mode of Action

Antioxidants are substances that either directly or indirectly protect cells against adverse effects of xenobiotics, drugs and carcinogens (1-5). Several biologically important compounds have been reported to have antioxidant functions. These include vitamin C (ascorbic acid), vitamin E, b-carotene, metallothionein, polyamines, melatonin, glutathione, superoxide dismutase and catalase (6-12). The antioxidant role of phenolic compounds including 3-( 2)-tert-butyl-4-hydroxyanisole (BHA), 3,5-di-tert-butyl-4-hydroxytoluene (BHT), and t-butyl hydroquinone (t-BHQ) in prevention of oxidative stress have been well documented (2-5). The various antioxidants either scavenge superoxide and free radicals or stimulate the detoxification mechanisms within cells resulting in prevention and increased detoxification of free radicals formation. Glutathione, superoxide dismutase and catalase directly scavenge superoxide, whereas BHA, BHT and t-BHQ coordinately induce the expression of a battery of genes, the products of which protect cells against oxidative stress and related consequences (13-21) (Fig. 1 and 2). Interestingly, many xenobiotics, oxidants, peroxides, UV light, and heavy metals also coordinately induce the expression of similar genes as observed with antioxidants (Fig. 1 and 2). Both, antioxidants and xenobiotics are metabolized by cellular enzymes to generate superoxide and electrophiles. It is believed that this initial generation of superoxide is to activate a battery of genes for cellular protection. Failure in this mechanism leads to the accumulation of superoxide and other free radicals. The accumulation of superoxide and other free radicals is known to cause oxidative stress, DNA and membrane damage, mutagenicity, degeneration of tissues, premature aging, apoptotic cell death, cellular transformation and cancer (13-21). This article focuses on the mechanisms by which antioxidants and xenobiotics induce the gene expression of detoxifying enzyme.


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[ABSTRACT] [Antioxidants and their Mode of Action] [Induction of Genes Encoding Enzymes that Detoxify Xenobiotics and Carcinogens.] [Antioxidant Response Element] [Figures] [Figures-2] [Antioxidant Response Element-Binding Proteins] [Summary and Conclusions] [Acknowledgements] [References] [Discussion Board]

ABSTRACT Previous: Phase II Enzyme Symposium Introduction Induction of Genes Encoding Enzymes that Detoxify Xenobiotics and Carcinogens.
Next: Glutathione deficiencies exacerbate response to stroke.
S. Dhakshinamoorthy, D. Bloom, Anil Jaiswal
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