Cytochrome-P450 enzymes and autoimmunity: expansion of the relationship and introduction of free radicals as the link

MR Namazi

doi:10.1186/1740-2557-6-4

Abstract

The Cytochrome-P-450 enzymes (CYP) are among the most important xenobiotic-metabolizing enzymes, which produce reactive oxygen species (ROS) as the result of metabolizing xenobiotics.ROS are believed to play important roles in the pathophysiology of autoimmune diseases. ROS can alter the structure of cellular antigens to produce a "neo-antigen" which could mount an autoimmune response against the original antigen through molecular mimicry. ROS are involved in apoptosis, activation of antigen presenting cells and initiation or amplification of diverse immunologic reactions.Taking all these facts together, it could be speculated that CYP may be involved in the initiation and/or amplification of autoimmune phenomena.

Highlights

Involvement of cytochrome P450 (CYP) enzymes in the pathogenesis of autoimmune hepatitis type 2, occurring via molecular mimicry of human cytochrome P450 by hepatitis C virus at the level of cytotoxic T cell recognition, is well appreciated [1]
Given that the metabolism of xenobiotics by CYP leads to the production of reactive oxygen species (ROS), and that ROS contribute crucially to the initiation and/or amplification of the autoimmune response, CYP may play a role in the pathobiology of some autoimmune diseases
Some cytochrome P450 (CYP) heme-thiolate enzymes participate in the detoxication of xenobiotics

Summary

Background

Involvement of cytochrome P450 (CYP) enzymes in the pathogenesis of autoimmune hepatitis type 2, occurring via molecular mimicry of human cytochrome P450 by hepatitis C virus at the level of cytotoxic T cell recognition, is well appreciated [1]. Cells generate ROS such as superoxide anion (O2.-) and H2O2 as a result of metabolism of xenobiotics by CYP Both O2.- and H2O2 may be converted to the highly reactive hydroxyl radical (OH.-) by iron (Fe2+)-catalyzed Haber-Weiss and Fenton reactions. Many xenobiotics are converted to toxic quinones by CYP enzymes (Figure 1) These quinones are redox sensitive agents and are reversibly reduced to semihydoquinones/ hydroquinone, which generate superoxide anion. B)The important role of ROS in the pathogenesis of autoimmunity There are several ways by which ROS could contribute to the development of autoimmunity These mechanisms, discussed fully in reference [9], are as follows: The structures of cellular macromolecules and small molecules may markedly change by acute or chronic oxidative stress, acting as antigens ("neo-antigens"). Oxidative stress plays an important role in the etiopathogenesis of the autoimmune diseases by initiating or amplifying the autoimmune response

Conclusion

Namazi MR

12. Grifiths HR