Mohammad Hossein Asghari1,2, Mohammad Abdollahi3,2, Marcos Roberto de Oliveira4, Seyed Mohammad Nabavi5. 1. Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran. 2. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 3. Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran, Iran. 4. Department of Chemistry/ICET, Federal University of Mato Grosso (UFMT), Cuiaba, MT, Brazil. 5. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Abstract
OBJECTIVES: Acute poisoning with aluminium phosphide (AlP) is a major cause of mortality in developing countries. AlP mortality is due to cardiac dysfunction leading to cardiomyocyte death. The main mechanism is an inhibition of cytochrome c oxidase in the cardiomyocyte mitochondria, resulting in a decreased ATP production and oxidative stress. Unfortunately, the administration of exogenous drugs does not meet the desired requirements of an effective therapy. Melatonin is an amphiphilic molecule and can easily pass through all cellular compartments with the highest concentration recorded in mitochondria. It is known as a vigorous antioxidant, acting as a potent reactive oxygen species (ROS) scavenger. Our aim is to summarize the mechanisms by which melatonin may modulate the deteriorating effects of AlP poisoning on cardiac mitochondria. KEY FINDINGS: Melatonin not only mitigates the inhibition of respiratory chain complexes, but also increases ATP generation. Moreover, it can directly inhibit the mitochondrial permeability transition pore (mPTP) opening, thus preventing apoptosis. In addition, melatonin inhibits the release of cytochrome c from mitochondria to hinder caspase activation leading to cell survival. SUMMARY: Based on the promising effects of melatonin on mitochondria, melatonin may mitigate AlP-induced cardiotoxicity and might be potentially suggested as cardioprotective in AlP-intoxicated patients.
OBJECTIVES: Acute poisoning with aluminium phosphide (AlP) is a major cause of mortality in developing countries. AlP mortality is due to cardiac dysfunction leading to cardiomyocyte death. The main mechanism is an inhibition of cytochrome c oxidase in the cardiomyocyte mitochondria, resulting in a decreased ATP production and oxidative stress. Unfortunately, the administration of exogenous drugs does not meet the desired requirements of an effective therapy. Melatonin is an amphiphilic molecule and can easily pass through all cellular compartments with the highest concentration recorded in mitochondria. It is known as a vigorous antioxidant, acting as a potent reactive oxygen species (ROS) scavenger. Our aim is to summarize the mechanisms by which melatonin may modulate the deteriorating effects of AlP poisoning on cardiac mitochondria. KEY FINDINGS:Melatonin not only mitigates the inhibition of respiratory chain complexes, but also increases ATP generation. Moreover, it can directly inhibit the mitochondrial permeability transition pore (mPTP) opening, thus preventing apoptosis. In addition, melatonin inhibits the release of cytochrome c from mitochondria to hinder caspase activation leading to cell survival. SUMMARY: Based on the promising effects of melatonin on mitochondria, melatonin may mitigate AlP-induced cardiotoxicity and might be potentially suggested as cardioprotective in AlP-intoxicated patients.
Authors: Remedios Guzmán-Guillén; María Puerto; Daniel Gutiérrez-Praena; Ana I Prieto; Silvia Pichardo; Ángeles Jos; Alexandre Campos; Vitor Vasconcelos; Ana M Cameán Journal: Toxins (Basel) Date: 2017-05-23 Impact factor: 4.546
Authors: Haixia Zhang; Xuan Liu; Ting Chen; Yazhen Ji; Kun Shi; Lin Wang; Xiaodong Zheng; Jin Kong Journal: Molecules Date: 2018-02-27 Impact factor: 4.411