On the mechanisms of melatonin in protection of aluminum phosphide cardiotoxicity

Abstract

Aluminum phosphide (AlP), one of the most commonly used pesticides worldwide, has been the leading cause of self-poisoning mortalities among many Asian countries. The heart is the main organ affected in AlP poisoning. Melatonin has been previously shown to be beneficial in reversing toxic changes in the heart. The present study reveals evidence on the probable protective effects of melatonin on AlP-induced cardiotoxicity in rats. The study groups included a control (almond oil only), ethanol 5% (solvent), sole melatonin (50 mg/kg), AlP (16.7 mg/kg), and 4 AlP + melatonin groups which received 20, 30, 40 and 50 mg/kg of melatonin by intraperitoneal injections following AlP treatment. An electronic cardiovascular monitoring device was used to record the electrocardiographic (ECG) parameters. Heart tissues were studied in terms of oxidative stress biomarkers, mitochondrial complexes activities, ADP/ATP ratio and apoptosis. Abnormal ECG records as well as declined heart rate and blood pressure were found to be related to AlP administration. Based on the results, melatonin was highly effective in controlling AlP-induced changes in the study groups. Significant improvements were observed in the activities of mitochondrial complexes, oxidative stress biomarkers, the activities of caspases 3 and 9, and ADP/ATP ratio following treatment with melatonin at doses of 40 and 50 mg/kg. Our results indicate that melatonin can counteract the AlP-induced oxidative damage in the heart. This is mainly done by maintaining the normal balance of intracellular ATP as well as the prevention of oxidative damage. Further research is warranted to evaluate the possibility of using melatonin as an antidote in AlP poisoning.

Antidotes for aluminum phosphide poisoning – An update

“…To estimate melatonin-attributed effects on 16.7 mg/kg AlP-induced decline in heart rate and blood pressure, several doses of melatonin (20, 30, 40 and 50 mg/kg; IP) were administered [ 41 ]. Significant improvements were observed in the activities of mitochondrial complexes, oxidative stress biomarkers and ADP/ATP ratio following 40 and 50 mg/kg melatonin administration.…”

Chrysin ameliorates aluminum phosphide‐induced oxidative stress and mitochondrial damages in rat cardiomyocytes and isolated mitochondria

“…Because mitochondria can play a pivotal role in all of the above mechanisms, it seems that mitochondrial toxicity be a key mechanism in AlP poisoning. The mitochondria‐related mechanisms of AlP‐induced cardiotoxicity have been extensively studied 9 . In recent years, accumulated documents demonstrate that small molecules found in plants have proven to be effective in chemical and drug‐induced cardiotoxicity and the use of natural small molecules targeting mitochondria to prevent cardiotoxicity has been extensively studied and has made considerable progress 10 …”

Adjuvant potential of selegiline in treating acute toxicity of aluminium phosphide in rats

“…Ample evidence indicates that poisoning with AlP causes cardiac toxicity and disturbances in ECG parameters such as prolongation of QT and PR intervals, QRS complex widening and ST changes . In most cases, failure in cardiac system is associated with high mortality rate in affected subjects.…”

“…Ample evidence indicates that poisoning with AlP causes cardiac toxicity and disturbances in ECG parameters such as prolongation of QT and PR intervals, QRS complex widening and ST changes. 16,[47][48][49] In most cases, failure in cardiac system is associated with high mortality rate in affected subjects. Previous studies revealed that cardiac toxicity is associated with metabolic acidosis and inflamed and dysmorphic mitochondria in cardiac tissue.…”