Cytochrome P450-Mediated Estrogen Metabolites and Autoimmunity: Relationship and Link to Free Radicals

Cytochrome P450 enzymes are responsible for the hydroxylation of various endogenous estrogens of the Phase I metabolic pathway. Cytochrome P450s produce hormonally active estrogen metabolites that are typically reactive and mutagenic. Although these metabolites are known to have important roles in a...

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Bibliographic Details
Published inCurrent drug metabolism Vol. 17; no. 1; p. 65
Main Authors Khan, Wahid Ali, Ali Khan, Mohd Wajid
Format Journal Article
LanguageEnglish
Published Netherlands 01.01.2016
Subjects
Animals
Autoimmunity - physiology
Cytochrome P-450 Enzyme System - immunology
Cytochrome P-450 Enzyme System - metabolism
Estrogens - immunology
Estrogens - metabolism
Free Radicals - immunology
Free Radicals - metabolism
Humans
Reactive Oxygen Species - metabolism
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Summary:Cytochrome P450 enzymes are responsible for the hydroxylation of various endogenous estrogens of the Phase I metabolic pathway. Cytochrome P450s produce hormonally active estrogen metabolites that are typically reactive and mutagenic. Although these metabolites are known to have important roles in autoimmunity, the underlying mechanism of this remains unknown. Here we report that cytochrome P450-mediated estrogen metabolites produce high ROS concentrations that can result in DNA damage. Such DNA damage can alter its immunogenicity, resulting in the induction and elevation of autoantibody concentrations, thus generating various autoimmune conditions. Here we focus on the mechanisms through which cytochrome P450-catalyzed estrogen metabolites induce immune responses and subsequently produce the autoimmune phenomenon.
ISSN:1875-5453
DOI:10.2174/1389200216666151103115210