Molecular and biochemical evidence on the protection of cardiomyocytes from phosphine-induced oxidative stress, mitochondrial dysfunction and apoptosis by acetyl-l-carnitine

The aim of the present study was to investigate the efficacy of acetyl-l-carnitine (ALCAR) on pathologicchanges of mitochondrial respiratory chain activity, ATP production, oxidative stress, and cellular apo-ptosis/necrosis induced by aluminum phosphide (AlP) poisoning. The study groups included: the Shamthat received almond oil only; the AlP that received oral LD50dose of aluminum; the AC-100, AC-200, andAC-300 which received concurrent oral LD50dose of AlP and single 100, 200, and 300 mg/kg of ALCAR byintraperitoneal injection. After 24 h, the rats were sacrificed; the heart and blood sample were taken formeasurement of biochemical and mitochondrial factors. The results specified that ALCAR significantlyattenuated the oxidative stress (elevated ROS and plasma iron levels) caused by AlP poisoning. ALCARalso increased the activity of cytochrome oxidase, which in turn amplified ATP production. Furthermore,flow cytometric assays and caspase activity indicated that ALCAR prohibited AlP-induced apoptosis incardiomyocytes.© 2015 Elsevier B.V. All rights reserved.1. IntroductionPesticide poisoning is accountable for annually 300,000 casu-alties around the world. Organophosphorus and metal phosphides(aluminum and zinc phosphide) keep the highest rate in thisregard. Aluminum phosphide (AlP) is widely used as an effectiveinsecticide and rodenticide (in the shape of tablets, pellets, etc.) toprotect stored grains (Mehrpour et al., 2012). Phosphine gas (PH3)generated from AlP combines with humidity in the air and playsthe pesticide role. PH3is colorless and odorless (though impuritiesin tablets cause garlic smell while sublimated). Moreover, phos-phine density is approximately equal to the air (1.17 times) that∗Corresponding author.E-mail