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Titre du document / Document title

Immunosuppression and oxidative stress induced by acute and chronic exposure to cocaine in rat

Auteur(s) / Author(s)

PACIFICI Roberta (1) ; FIASCHI Anna Ida (2) ; MICHELI Lucia (2) ; CENTINI Fabio (3) ; GIORGI Giorgio (2) ; ZUCCARO Piergiorgio (1) ; PICHINI Simona (1) ; DI CARLO Simonetta (1) ; BACOSI Antonella (1) ; CERRETANI Daniela (2) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Clinical Biochemistry Department, Istituto Superiore di Sanità, V.le Regina Elena 299, 00161 Rome, ITALIE
(2) Department of Pharmacology G. Segre University of Siena, Siena, ITALIE
(3) Division of Forensic Toxicology, University of Siena, Siena, ITALIE

Résumé / Abstract

The objective of the present study was to verify if immunosuppression caused by cocaine (CO) can be mediated, at least in part, by increased formation of oxidative metabolites and reactive oxygen species (ROS) in rat. Pharmacokinetics of cocaine and its metabolites, cell-mediated immune function and cytokines production, biomarkers of cell redox state maintenance and lipidic peroxidation, and variations of activity in the enzymatic systems involved in cell antioxidant defence were measured in spleen of Wistar rats acutely and chronically treated with cocaine. Cmax, AUC, and 11/2 of norcocaine (NC) significantly increased after chronic exposure to cocaine while kinetic parameters of benzoylecgonine (BE) significantly decreased. A decrease in cultured T-lymphocytes proliferation and natural killer (NK) cell activity, a high increase of immunosuppressive cytokines and a switch from Th1-type cytokines to Th2-type cytokines together with an unbalance toward anti-inflammatory cytokines recovered within 4 h after acute treatment while subsisted for 14 days after chronic treatment. A significant increase in ascorbic acid (AA), reduced glutathione and glutathione reductase (GR) with a simultaneous decrease in oxidized glutathione were observed in the first hours after acute administration. Conversely, the increase in oxidized glutathione and malondialdehyde (MDA) production and the simultaneous depletion of reduced glutathione and ascorbic acid persisted at least 24 h after chronic cocaine treatment as well as the increase in the activities of glutathione reductase, glutathione peroxidase (GPx) and superoxide dismutase (SOD). The results suggest that chronic cocaine administration affects cellular enzyme and non-enzyme-mediated antioxidant defence systems and promotes immunotoxicity in rat. Cocaine N-oxidative metabolism may be an indirect contributor, via oxidative stress.

Revue / Journal Title

International immunopharmacology    ISSN  1567-5769 

Source / Source

2003, vol. 3, no4, pp. 581-592 [12 page(s) (article)] (41 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Kidlington, ROYAUME-UNI  (2001) (Revue)

Mots-clés anglais / English Keywords

Vertebrata

;

Mammalia

;

Rodentia

;

Antioxidant

;

Enzyme

;

Ester

;

Free radical

;

Oxidative stress

;

Mechanism of action

;

Immune response

;

Immunosuppression

;

Chronic

;

Multiple dose

;

Single dose

;

Administration schedule

;

Comparative study

;

Drug of abuse

;

Intraperitoneal administration

;

Toxicity

;

Rat

;

Animal

;

Cocaine

;

Mots-clés français / French Keywords

Vertebrata

;

Mammalia

;

Rodentia

;

Antioxydant

;

Enzyme

;

Ester

;

Radical libre

;

Stress oxydatif

;

Mécanisme action

;

Réponse immune

;

Immunodépression

;

Chronique

;

Dose répétée

;

Dose unique

;

Rythme administration

;

Etude comparative

;

Substance toxicomanogène

;

Voie intrapéritonéale

;

Toxicité

;

Rat

;

Animal

;

Cocaïne

;

Mots-clés espagnols / Spanish Keywords

Vertebrata

;

Mammalia

;

Rodentia

;

Antioxidante

;

Enzima

;

Ester

;

Radical libre

;

Estrés oxidativo

;

Mecanismo acción

;

Respuesta inmune

;

Inmunodepresión

;

Crónico

;

Dosis múltiple

;

Dosis única

;

Ritmo administración

;

Estudio comparativo

;

Sustancia toxicomanógena

;

Vía intraperitoneal

;

Toxicidad

;

Rata

;

Animal

;

Cocaína

;

Mots-clés d'auteur / Author Keywords

Cocaine

;

Immune function

;

Oxidative stress

;

Oxidative metabolites

;

Reactive oxygen species

;

Rat spleen

;

Localisation / Location

INIST-CNRS, Cote INIST : 27109, 35400011094480.0120

Nº notice refdoc (ud4) : 14680131



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