Selenium diet-supplementation improves cocaine-induced myocardial oxidative stress and prevents cardiac dysfunction in rats.
Chronic cocaine abuse causes cardiac dysfunction and induces oxidative stress. The goal of this study was to evaluate whether an enhanced antioxidant pool, induced by the administration of selenium, may prevent the myocardial dysfunction induced by cocaine. Cocaine was administered for 7 days (15 mg/kg/day, i.p.) to rats pretreated for 4 weeks with selenium (1.16 mg/L/day, p.o.). Cardiac function was evaluated by cardiac index and left ventricular (LV) fractional shortening (FS) measured by echocardiography. The redox ratio and enzymatic activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured in the LV myocardium. Cocaine administration induced a cardiac dysfunction, as evidenced by a decrease in cardiac index and LV FS as well as by an increase in LV diameters. Moreover, antioxidant markers and redox ratio were altered in rats after cocaine exposure. Selenite supplementation induced a significant limitation of cardiac index and FS alterations observed after cocaine administration. This improvement in cardiac function was associated with a redox ratio recovery while SOD and GPX activities remained unchanged. Thus, selenite reversed both the oxidative stress and the contractile dysfunction induced by cocaine administration. These results suggest a major role of oxidative stress in the cocaine-induced cardiotoxicity.
INSERM E9920 (IFRMP n degrees 23) UFR de Médecine et de Pharmacie, 22 boulevard Gambetta, 76183 Rouen, France.
Fabienne
F
Moritz
Christelle
C
Monteil
Marc
M
Isabelle
Paul
P
Mulder
Jean-Paul
JP
Henry
Geneviève
G
Derumeaux
Vincent
V
Richard
Jean-Michel
JM
Muller
Christian
C
Thuillez
D000818:Animals; D019970:Cocaine-Related Disorders / Q000150:complications* / Q000201:enzymology; D004032:Diet; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000008:administration & dosage / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000517:prevention & control*
D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D012643:Selenium