uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
The chemical defensive system in the pathobiology of idiopathic environment-associated diseases
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
Show others and affiliations
2009 (English)In: Current drug metabolism, ISSN 1389-2002, Vol. 10, no 8, 914-931 p.Article, review/survey (Refereed) Published
Abstract [en]

Chemical defensive system consisting of bio-sensoring, transmitting, and responsive elements has been evolved to protect multi-cellular organisms against environmental chemical insults (xenobiotics) and to maintain homeostasis of endogenous low molecular weight metabolites (endobiotics). Both genetic and epigenetic defects of the system in association with carcinogenesis and individual sensitivity to anti-tumor therapies have been intensely studied. Recently, several non-tumor human pathologies with evident environmental components such as rather rare functional syndromes (multiple chemical sensitivity, chronic fatigue, Persian Gulf, and fibromyalgia now collectively labeled as idiopathic environmental intolerances) and common diseases (vitiligo and systemic lupus erythematosus) have become subjects of the research on the impaired metabolism and detoxification of xenobiotics and endogenous toxins. Here, we collected and critically reviewed epidemiological, genetic, and biochemical data on the involvement and possible role of cytochrome P450 super family enzymes, glutathione-S-transferase isozymes, catechol-O-methyl-transferase, UDP-glucuronosyl transferases, and proteins detoxifying inorganic and organic peroxides (catalase, glutathione peroxidase, and peroxiredoxin) in the above pathologies. Genetic predisposition assessed mainly by single nucleotide polymorphism and gene expression analyses revealed correlations between defects in genes encoding xenobiotic-metabolizing and/or detoxifying enzymes and risk/severity of these syndromes/diseases. Proteome analysis identified abnormal expression of the enzymes. Their functions were affected epigenetically leading to metabolic impairment and, as a consequence, to the negative health outcomes shared by some of these pathologies. Data obtained so far suggest that distinct components of the chemical defensive system could be suitable molecular targets for future pathogenic therapies.

Place, publisher, year, edition, pages
2009. Vol. 10, no 8, 914-931 p.
Keyword [en]
Catalase, CYPs, genetic polymorphism, GSTs, idiopathic environmental intolerances, systemic lupus erythematosus, UGTs, vitiligo
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-124200ISI: 000273742300010PubMedID: 20201826OAI: oai:DiVA.org:uu-124200DiVA: diva2:317229
Available from: 2010-05-03 Created: 2010-05-03 Last updated: 2011-03-17Bibliographically approved

Open Access in DiVA

No full text

By organisation
Clinical Pharmacology
In the same journal
Current drug metabolism
Pharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 155 hits
ReferencesLink to record
Permanent link

Direct link