Journal
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
Volume 128, Issue 2, Pages 322-333Publisher
WILEY
DOI: 10.1111/bcpt.13500
Keywords
Cyclosporine A; Mitochondria; MitoTEMPO; Nicotine; Superoxide Dismutase
Categories
Funding
- Universiti Kebangsaan Malaysia [GGPM-2011-095, GUP-2013-008]
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This study found that prolonged nicotine administration increases myocardial susceptibility to I/R injury in rats, which is associated with increased mitochondrial permeability transition driven by ROS.
This study investigated the impact of prolonged nicotine administration on myocardial susceptibility to ischaemia-reperfusion (I/R) injury in a rat model and determined whether nicotine affects mitochondrial reactive oxygen species (ROS) production and permeability transition in rat hearts. Sprague-Dawley rats were administered 0.6 or 1.2 mg/kg nicotine for 28 days, and their hearts were isolated at end-point for assessment of myocardial susceptibility to I/R injury ex vivo. Rat heart mitochondria were also isolated from a subset of rats for analysis of mitochondrial ROS production and permeability transition. Compared to the vehicle controls, rat hearts isolated from nicotine-administered rats exhibited poorer left ventricular function that worsened over the course of I/R. Coronary flow rate was also severely impaired in the nicotine groups at baseline and this worsened after I/R. Nicotine administration significantly increased mitochondrial ROS production and permeability transition relative to the vehicle controls. Interestingly, pre-incubation of isolated mitochondria with ROS scavengers (superoxide dismutase and mitoTEMPO) significantly abolished nicotine-induced increase in mitochondria permeability transition in isolated rat heart mitochondria. Overall, our data showed that prolonged nicotine administration enhances myocardial susceptibility to I/R injury in rats and this is associated with mitochondrial ROS-driven increase in mitochondrial permeability transition.
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