title: Role of reactive oxygen species in cocaine-induced cardiac dysfunction.
abstract: OBJECTIVE
  Contractility alterations and LV hypertrophy after chronic cocaine administration have been shown to be accompanied by an increase in oxidative stress. This study was carried out to investigate whether the production of reactive oxygen species is an early event of primary importance in cocaine-induced myocardial injury or simply occurs as a consequence of the ventricular dysfunction itself.
  
  
  RESULTS
  After 2 days of cocaine administration to rats, no differences were observed in echocardiographic parameters between the cocaine-treated group and the control group. However, an increase in oxidative stress in the myocardium was indicated by an increase in lipid peroxidation (+35%, cocaine vs. control), an increase in antioxidant enzymes (catalase +110%, glutathione peroxidase +40% and superoxide dismutase +38%) and of NADPH-driven superoxide production (assessed by chemiluminescence). Furthermore, higher gp91phox and p22phox mRNA expression, measured by quantitative real-time RT-PCR, was found in the cocaine group. On day 8, cocaine administration induced a cardiac dysfunction, characterized by a decrease in cardiac index (-30%, cocaine vs. controls) and left ventricular (LV) fractional shortening (-23%, cocaine vs. controls). This LV dysfunction was prevented by antioxidant treatment (100 mg/kg/day vitamin C and 100 U/kg/day vitamin E). Moreover, in these animals, antioxidant treatment decreased lipid peroxides and decreased the activity of NADPH oxidase, associated with the downregulation of gp91phox.
  
  
  CONCLUSIONS
  These data indicate that cocaine administration induces early NADPH-driven O2-. release which may play an important role in the development and progression of the LV dysfunction observed after chronic cocaine abuse.
authors.affiliation: INSERM E9920, Faculté de médecine-Pharmacie de Rouen, IFRMP n degrees 23, University Medical School, 22 boulevard Gambetta, 76183 Rouen, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Moritz
authors.forename: Christelle
authors.initials: C
authors.lastname: Monteil
authors.forename: Marc
authors.initials: M
authors.lastname: Isabelle
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bauer
authors.forename: Sylvanie
authors.initials: S
authors.lastname: Renet
authors.forename: Paul
authors.initials: P
authors.lastname: Mulder
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage; D003042:Cocaine / Q000494:pharmacology*; D004452:Echocardiography; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D014810:Vitamin E; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D003042:Cocaine; D001205:Ascorbic Acid