title: Myocardial oxidative damage is induced by cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose.
abstract: The aim of this study is to analyse cardiac specimens from human cocaine-related overdose, to verify the hypothesis that cardiac toxicity by acute exposure to high dosage of cocaine could be mediated by unbalanced myocardial oxidative stress, and to evaluate the apoptotic response. To address these issues, biochemical and immunohistological markers of oxidative/nitrosative stress were evaluated. We found that i-NOS, NOX2 and nitrotyrosine expression were significantly higher in the hearts of subjects who had died from high doses of cocaine, compared to the control group. Increase of these markers was associated with a dramatic increase in 8-OHdG, another marker of oxidative stress. A high number of TUNEL-positive apoptotic myocells was observed in the study group compared to the control group. The immunoexpression of TNF-α was significantly higher in the cocaine group compared to the control group. Furthermore, we detected a significantly stronger immunoresponse to anti-SMAC/DIABLO in our study group compared to control cases. Both cardiac Fas-dependent and mitochondria-dependent apoptotic pathways appeared to be activated to a greater extent in the cocaine group than in the control group. Our results highlight the central role of oxidative stress in cocaine toxicity. High levels of NOS can promote the oxidation process and lead to apoptosis.
authors.affiliation: Institute of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia - Viale Pinto 1, 71121 Foggia, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Turillazzi
authors.affiliation: Department of Medical and Surgical Sciences and Neurosciences, University of Siena - Viale Mario Bracci 16, 53100 Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cerretani
authors.affiliation: Institute of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia - Viale Pinto 1, 71121 Foggia, Italy.
authors.forename: Santina
authors.initials: S
authors.lastname: Cantatore
authors.affiliation: Department of Medical and Surgical Sciences and Neurosciences, University of Siena - Viale Mario Bracci 16, 53100 Siena, Italy.
authors.forename: Anna Ida
authors.initials: AI
authors.lastname: Fiaschi
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, S apienza University of Rome - Viale Regina Elena 336, 00185 Rome, Italy.|Neuromed, Istituto Mediterraneo Neurologico (IRCCS) - Via Atinense 18, Pozzilli, 86077 Isernia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Frati
authors.affiliation: Department of Medical and Surgical Sciences and Neurosciences, University of Siena - Viale Mario Bracci 16, 53100 Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Micheli
authors.affiliation: Department of Morphology, Experimental Medicine and Surgery, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Neri
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, S apienza University of Rome - Viale Regina Elena 336, 00185 Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cipolloni
authors.affiliation: Institute of Legal Medicine, Department of Clinical and Experimental Medicine, University of Pisa - Via Roma 55, 56126 Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Di Paolo
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, S apienza University of Rome - Viale Regina Elena 336, 00185 Rome, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Pinchi
authors.affiliation: Institute of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia - Viale Pinto 1, 71121 Foggia, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Riezzo
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, S apienza University of Rome - Viale Regina Elena 336, 00185 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Santurro
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, S apienza University of Rome - Viale Regina Elena 336, 00185 Rome, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Vullo
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, S apienza University of Rome - Viale Regina Elena 336, 00185 Rome, Italy.|Neuromed, Istituto Mediterraneo Neurologico (IRCCS) - Via Atinense 18, Pozzilli, 86077 Isernia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Fineschi
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001344:Autopsy; D003042:Cocaine / Q000506:poisoning; D019970:Cocaine-Related Disorders / Q000378:metabolism; D062787:Drug Overdose / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction; D055815:Young Adult; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D019014:fas Receptor; D052247:Nitric Oxide Synthase Type II; D003042:Cocaine