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domenica 16 maggio 2010

Definizione biologica della Sensibilità Chimica Multipla: studio sui malati di MCS

Ad aprile un'équipe di ricercatori del Policlinico Umberto 1°, dell'IDI, dell'Università di Siena e dell'Università di Upssala (Svezia) ha pubblicato una ricerca effettuata sui malati  di MCS

Definizione biologica della sensibilità multipla chimica dallo stato redox e dal profilo delle citochine e non dai polimorfismi degli enzimi che metabolizzano gli xenobiotici
Toxicology and applied pharmacology (26 April 2010)
Chiara De Luca, Maria G. Scordo, Eleonora Cesareo, Saveria Pastore, Serena Mariani, Gianluca Maiani, Andrea Stancato, Beatrice Loreti, Giuseppe Valacchi, Carla Lubrano, Desanka Raskovic, Luigia De Padova, Giuseppe Genovesi, Liudmila G. Korkina 
AbstractBackground
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.

Fonte: pubmed
Foto: medicinalive

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