title: Toxicity of lithium on isolated heart mitochondria and cardiomyocyte: A justification for its cardiotoxic adverse effect.
abstract: 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.
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Students Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran.
authors: Ahmad
authors: A
authors: Salimi
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Ehsan
authors: E
authors: Gholamifar
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran.
authors: Parvaneh
authors: P
authors: Naserzadeh
authors: Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.|Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors: Mir-Jamal
authors: MJ
authors: Hosseini
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Jalal
authors: J
authors: Pourahmad
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D018020:Lithium Compounds / Q000633:toxicity*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D018020:Lithium Compounds; D017382:Reactive Oxygen Species; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D013385:Succinate Dehydrogenase; D053148:Caspase 3; D020782:Matrix Metalloproteinases
keywords: Lithium; apoptosis; cardiotoxicity; mitochondrial dysfunction