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: Reza Solgi, Amir Baghaei, Ali Golaghaei, Shokoufeh Hasani, Maryam Baeeri, Mona Navaei, Seyyed Nasser Ostad, Rohollah Hosseini, Mohammad Abdollahi
• Journal: Toxicology mechanisms and methods (Toxicol Mech Methods) Vol. 25 Issue 4 Pg. 249-57 ( 2015) ISSN: 1537-6524 [Electronic] England
• PMID: 25906050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Cardiotonic Agents
• Ferric Compounds
• Insecticides
• Phosphines
• Hydroxyl Radical
• Adenosine Diphosphate
• Adenosine Triphosphate
• phosphine
• Ferric Oxide, Saccharated
• Glucaric Acid

Topics

• Adenosine Diphosphate (metabolism)
• Adenosine Triphosphate (metabolism)
• Animals
• Antioxidants (metabolism)
• Apoptosis (drug effects)
• Cardiotonic Agents (therapeutic use)
• Cell Death (drug effects)
• Electrocardiography (drug effects)
• Ferric Compounds (therapeutic use)
• Ferric Oxide, Saccharated
• Glucaric Acid (therapeutic use)
• Heart Diseases (chemically induced, pathology, prevention & control)
• Heart Rate (drug effects)
• Hydroxyl Radical (metabolism)
• Insecticides (toxicity)
• Lipid Peroxidation (drug effects)
• Male
• Mitochondria, Heart (drug effects, metabolism)
• Myocardium (metabolism, pathology)
• Phosphines (antagonists & inhibitors, toxicity)
• Rats
• Rats, Wistar