Biological definition of multiple chemical sensitivity from redox state and cytokine profiling and not from polymorphisms of xenobiotic-metabolizing enzymes

Journal Article · Mon Nov 01 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.04.017· OSTI ID:21460233

De Luca, Chiara ^[1]; Scordo, Maria G ^[2]; Cesareo, Eleonora; Pastore, Saveria; Mariani, Serena; Maiani, Gianluca; Stancato, Andrea ^[1]; Loreti, Beatrice ^[3]; Valacchi, Giuseppe ^[4]; Lubrano, Carla ^[3]; Raskovic, Desanka ^[5]; De Padova, Luigia; Genovesi, Giuseppe ^[3]

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1. Laboratory of Tissue Engineering and Skin Pathophysiology, Dermatology Institute (IDI IRCCS), Rome (Italy)
2. Department of Medical Sciences, Clinical Pharmacology, University Hospital, Uppsala (Sweden)
3. Department of Medical Pathophysiology, University of Rome 'La Sapienza', Policlinico Umberto I, Rome (Italy)
4. Department of Biomedical Sciences, Siena University (Italy)
5. 2nd Division of Dermatology, Dermatology Institute (IDI IRCCS), Rome (Italy)

Background: Multiple chemical sensitivity (MCS) is a poorly clinically and biologically defined environment-associated syndrome. Although dysfunctions of phase I/phase II metabolizing enzymes and redox imbalance have been hypothesized, corresponding genetic and metabolic parameters in MCS have not been systematically examined. Objectives: We sought for genetic, immunological, and metabolic markers in MCS. Methods: We genotyped patients with diagnosis of MCS, suspected MCS and Italian healthy controls for allelic variants of cytochrome P450 isoforms (CYP2C9, CYP2C19, CYP2D6, and CYP3A5), UDP-glucuronosyl transferase (UGT1A1), and glutathione S-transferases (GSTP1, GSTM1, and GSTT1). Erythrocyte membrane fatty acids, antioxidant (catalase, superoxide dismutase (SOD)) and glutathione metabolizing (GST, glutathione peroxidase (Gpx)) enzymes, whole blood chemiluminescence, total antioxidant capacity, levels of nitrites/nitrates, glutathione, HNE-protein adducts, and a wide spectrum of cytokines in the plasma were determined. Results: Allele and genotype frequencies of CYPs, UGT, GSTM, GSTT, and GSTP were similar in the Italian MCS patients and in the control populations. The activities of erythrocyte catalase and GST were lower, whereas Gpx was higher than normal. Both reduced and oxidised glutathione were decreased, whereas nitrites/nitrates were increased in the MCS groups. The MCS fatty acid profile was shifted to saturated compartment and IFNgamma, IL-8, IL-10, MCP-1, PDGFbb, and VEGF were increased. Conclusions: Altered redox and cytokine patterns suggest inhibition of expression/activity of metabolizing and antioxidant enzymes in MCS. Metabolic parameters indicating accelerated lipid oxidation, increased nitric oxide production and glutathione depletion in combination with increased plasma inflammatory cytokines should be considered in biological definition and diagnosis of MCS.

• OSTI ID: 21460233
• Journal Information: Toxicology and Applied Pharmacology, Vol. 248, Issue 3; Other Information: DOI: 10.1016/j.taap.2010.04.017; PII: S0041-008X(10)00144-4; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARBOXYLIC ACIDS
CATALASE
CHEMILUMINESCENCE
GLUTATHIONE
SENSITIVITY
SUPEROXIDE DISMUTASE
TRANSFERASES
DRUGS
EMISSION
ENZYMES
LUMINESCENCE
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PEPTIDES
PEROXIDASES
PHOTON EMISSION
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS