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Updated: May 5, 2026

A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
Chronic methamphetamine exposure induces cardiac fas-dependent and mitochondria-dependent apoptosis
Cher-Ming Liou1, Shiow-Chwen Tsai, Chia-Hua Kuo
1Department of Anesthesiology, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan.
Abstract:
Very limited information regarding the influence of chronic methamphetamine exposure on cardiac apoptosis is available. In this study, we evaluate whether chronic methamphetamine exposure will increase cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways. Thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group [phosphate-buffered saline (PBS) 0.5 ml SQ per day] and a methamphetamine-treated group (MA 10 mg/kg SQ per day) for 3 months. We report that after 3 months of exposure, abnormal myocardial architecture, more minor cardiac fibrosis and cardiac TUNEL-positive apoptotic cells were observed at greater frequency in the MA group than in the PBS group. Protein levels of TNF-α, Fas ligand, Fas receptor, Fas-associated death domain, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts were significantly increased in the MA 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, compared with the PBS group. The results from this study reveal that chronic methamphetamine exposure will activate cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which may indicate a possible mechanism for developing cardiac abnormalities in humans with chronic methamphetamine abuse.
Insights
Chronic methamphetamine exposure triggers cardiac cell death through both Fas-dependent and mitochondria-dependent pathways. This study reveals potential mechanisms for heart damage in methamphetamine abusers.
Area of Science:
- Cardiovascular pathology
- Toxicology
- Cellular biology
Background:
- Limited data exists on chronic methamphetamine's cardiac effects.
- Methamphetamine abuse is a public health concern with potential cardiac implications.
Purpose of the Study:
- To investigate the impact of chronic methamphetamine exposure on cardiac apoptosis.
- To determine if methamphetamine activates Fas-dependent (Type I) and mitochondria-dependent (Type II) apoptotic pathways in the heart.
Main Methods:
- Male Wistar rats were administered methamphetamine (10 mg/kg) or vehicle (PBS) daily for 3 months.
- Cardiac tissue was analyzed for structural changes, fibrosis, and apoptosis (TUNEL assay).
- Protein levels of key apoptotic markers (caspases, TNF-α, Fas pathway proteins, Bcl-2 family proteins) were quantified.
Main Results:
- Methamphetamine-treated rats exhibited abnormal myocardial architecture, increased fibrosis, and higher TUNEL-positive apoptotic cells.
- Significant increases in Fas-dependent apoptosis markers (TNF-α, Fas ligand, Fas receptor, FADD, activated caspase-8, activated caspase-3) were observed.
- Significant increases in mitochondria-dependent apoptosis markers (Bak, t-Bid, Bak/Bcl-xL ratio, activated caspase-9, activated caspase-3) were noted.
Conclusions:
- Chronic methamphetamine exposure activates both Fas-dependent and mitochondria-dependent apoptotic pathways in the heart.
- These activated pathways represent a potential mechanism underlying cardiac abnormalities in chronic methamphetamine users.
- Further research is warranted to explore therapeutic strategies targeting these apoptotic pathways.
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