Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
Arch Toxicol. 2017 Sep;91(9):3109-3120. doi: 10.1007/s00204-017-1998-6. Epub 2017 May 27.
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.
磷化铝(AlP)是世界上使用最广泛的杀虫剂之一,也是许多亚洲国家导致自杀性中毒死亡的主要原因。心脏是 AlP 中毒的主要受影响器官。褪黑素先前已被证明对逆转心脏毒性变化有益。本研究揭示了褪黑素对大鼠 AlP 诱导的心脏毒性可能具有保护作用的证据。研究组包括对照组(仅食用杏仁油)、5%乙醇(溶剂)、单独褪黑素(50mg/kg)、AlP(16.7mg/kg)以及 4 个 AlP+褪黑素组,这些组在 AlP 处理后通过腹腔注射分别接受 20、30、40 和 50mg/kg 的褪黑素。使用电子心血管监测设备记录心电图(ECG)参数。从氧化应激生物标志物、线粒体复合物活性、ADP/ATP 比和细胞凋亡等方面研究心脏组织。发现异常 ECG 记录以及心率和血压下降与 AlP 给药有关。根据结果,褪黑素在控制研究组中 AlP 诱导的变化方面非常有效。在褪黑素以 40 和 50mg/kg 剂量治疗后,观察到线粒体复合物活性、氧化应激生物标志物、半胱天冬酶 3 和 9 的活性以及 ADP/ATP 比显著改善。我们的研究结果表明,褪黑素可以对抗 AlP 诱导的心脏氧化损伤。这主要是通过维持细胞内 ATP 的正常平衡以及防止氧化损伤来实现的。需要进一步研究来评估将褪黑素用作 AlP 中毒解毒剂的可能性。