Cardiac Fas-dependent and Mitochondria-dependent Apoptosis after chronic methamphetamine and cocaine abuse

• Main Authors: Cher-Ming Liou, 劉哲銘
• Other Authors: 丁化
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/26142929679635992913

博士 === 中山醫學大學 === 醫學研究所 === 102 === Objective：The purpose of this study is to evaluate whether long-term methamphetamine, cocaine abuse will increase cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways. Methods and Materials：Thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5ml, SQ per day), a methamphetamine-treated group (MA, 10mg/kg SQ per day) and a cocaine-treated group (Cocaine, 10mg/Kg, SQ per day). After three months of treatment, the myocardial architecture and two major apoptotic pathways in the excised left ventricles were measured by histopathological analysis, Western blotting, DAPI staining and TUNEL assays. Results：Abnormal myocardial architecture, enlarged interstitial spaces, more minor cardiac fibrosis and cardiac TUNEL-positive apoptotic cells were observed at greater frequency in the MA group, Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts were significantly increased in the MA group, Cocaine group, compared to the PBS group. Protein levels of cardiac Bak, t-Bid, Bak-to-Bcl-xL ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the MA group; protein levels of cardiac Bax, cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the Cocaine group; compared to the PBS group. Conclusion and Suggestion：Chronic methamphetamine, cocaine exposure will activate the cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with long-term methamphetamine, cocaine abuse.