Electrophysiological and Molecular Mechanisms of Protection by Iron Sucrose Against Phosphine-Induced Cardiotoxicity: A Time Course Study Publisher Pubmed



Solgi R^{1, 2} ; Baghaei A¹ ; Golaghaei A¹ ; Hasani S¹ ; Baeeri M¹ ; Navaei M¹ ; Ostad SN¹ ; Hosseini R¹ ; Abdollahi M¹ Show Affiliations
Source: Toxicology Mechanisms and Methods Published:2015

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. © 2015 Informa Healthcare USA, Inc. All rights reserved.