title: Electrophysiological and molecular mechanisms of protection by iron sucrose against phosphine-induced cardiotoxicity: a time course study.
abstract: The present study was designed for determining the exact mechanism of cytotoxic action of aluminum phosphide (AlP) in the presence of iron sucrose as the proposed antidote. Rats received AlP (12 mg/kg) and iron sucrose (5-30 mg/kg) in various sets and were connected to cardiovascular monitoring device. After identification of optimum doses of AlP and iron sucrose, rats taken in 18 groups received AlP (6 mg/kg) and iron sucrose (10 mg/kg), treated at six different time points, and then their hearts were surgically removed and used for evaluating a series of mitochondrial parameters, including cell lipid peroxidation, antioxidant power, mitochondrial complex activity, ADP/ATP ratio and process of apoptosis. ECG changes of AlP poisoning, including QRS, QT, P-R, ST, BP and HR were ameliorated by iron sucrose (10 mg/kg) treatment. AlP initiated its toxicity in the heart mitochondria through reducing mitochondrial complexes (II, IV and V), which was followed by increasing lipid peroxidation and the ADP/ATP ratio and declining mitochondrial membrane integrity that ultimately resulted in cell death. AlP in acute exposure (6 mg/kg) resulted in an increase in hydroxyl radicals and lipid peroxidation in a time-dependent fashion, suggesting an interaction of delivering electrons of phosphine with mitochondrial respiratory chain and oxidative stress. Iron sucrose, as an electron receiver, can compete with mitochondrial respiratory chain complexes and divert electrons to another pathway. The present findings supported the idea that iron sucrose could normalize the activity of mitochondrial electron transfer chain and cellular ATP level as vital factors for cell escaping from AlP poisoning.
authors.affiliation: a Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center , Tehran University of Medical Sciences , Tehran , Iran and.
authors.forename: Reza
authors.initials: R
authors.lastname: Solgi
authors.forename: Amir
authors.initials: A
authors.lastname: Baghaei
authors.forename: Ali
authors.initials: A
authors.lastname: Golaghaei
authors.forename: Shokoufeh
authors.initials: S
authors.lastname: Hasani
authors.forename: Maryam
authors.initials: M
authors.lastname: Baeeri
authors.forename: Mona
authors.initials: M
authors.lastname: Navaei
authors.forename: Seyyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.forename: Rohollah
authors.initials: R
authors.lastname: Hosseini
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D005290:Ferric Compounds / Q000627:therapeutic use*; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid / Q000627:therapeutic use*; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D017665:Hydroxyl Radical / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010720:Phosphines / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D005290:Ferric Compounds; D007306:Insecticides; D010720:Phosphines; D017665:Hydroxyl Radical; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C044646:phosphine; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid
keywords: Complex IV; cytochrome C oxidase; iron sucrose; phosphine