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Toxicity of lithium on isolated heart mitochondria and cardiomyocyte: A justification for its cardiotoxic adverse effect
Author(s) -
Salimi Ahmad,
Gholamifar Ehsan,
Naserzadeh Parvaneh,
Hosseini MirJamal,
Pourahmad Jalal
Publication year - 2017
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21836
Subject(s) - mitochondrion , oxidative stress , cytochrome c , reactive oxygen species , pharmacology , apoptosis , lipid peroxidation , microbiology and biotechnology , programmed cell death , mitochondrial ros , chemistry , lithium (medication) , myocyte , membrane potential , biology , biochemistry , endocrinology
Mitochondria play an important role in myocardial tissue homeostasis; therefore, deterioration in mitochondrial function will eventually lead to cardiomyocyte and endothelial cell death and consequently cardiovascular dysfunction. Lithium (Li + ) is an effective drug for bipolar disorder with known cardiotoxic side effects. This study was designed to investigate the effects of Li + on mitochondria and cardiomyocytes isolated from the heart of Wistar rat. Results revealed that Li + induced a concentration‐ and time‐dependent rise in mitochondrial ROS formation, inhibition of respiratory complexes (II), mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release in rat heart mitochondria and also induced Caspase 3 activation through mitochondrial pathway, decline of ATP and lipid peroxidation in rat cardiomyocytes. These results indicate that the cardiotoxic effects of Li + were initiated from mitochondrial dysfunction and oxidative stress, which finally ends in cytochrome c release and cell death signaling heart cardiomyocytes.