Mechanisms of muscular electrophysiological and mitochondrial dysfunction following exposure to malathion, an organophosphorus pesticide

Abstract

<jats:p> Muscle dysfunction in acute organophosphorus (OP) poisoning is a cause of death in human. The present study was conducted to identify the mechanism of action of OP in terms of muscle mitochondrial dysfunction. Electromyography (EMG) was conducted on rats exposed to the acute oral dose of malathion (400 mg/kg) that could inhibit acetylcholinesterase activity up to 70%. The function of mitochondrial respiratory chain and the rate of production of reactive oxygen species (ROS) from intact mitochondria were measured. The bioenergetic pathways were studied by measurement of adenosine triphosphate (ATP), lactate, and glycogen. To identify mitochondrial-dependent apoptotic pathways, the messenger RNA (mRNA) expression of bax and bcl-2, protein expression of caspase-9, mitochondrial cytochrome c release, and DNA damage were measured. The EMG confirmed muscle weakness. The reduction in activity of mitochondrial complexes and muscular glycogen with an elevation of lactate was in association with impairment of cellular respiration. The reduction in mitochondrial proapoptotic stimuli is indicative of autophagic process inducing cytoprotective effects in the early stage of stress. Downregulation of apoptotic signaling may be due to reduction in ATP and ROS, and genotoxic potential of malathion. The maintenance of mitochondrial integrity by means of artificial electron donors and increasing exogenous ATP might prevent toxicity of OPs. </jats:p>

Clinical analysis of penehyclidine hydrochloride combined with hemoperfusion in the treatment of acute severe organophosphorus pesticide poisoning

“…The mechanism of organophosphorus pesticide poisoning involves entry of the organophosphorus pesticide into the body and combination with cholinesterase to form a stable phosphorylated cholinesterase, which cannot be broken down by acetylcholine, and thus, leads to accumulation of large amounts of phosphatidylcholine in the body and causes muscarinic, nicotinic, and central nervous system symptoms (Karami-Mohajeri et al, 2014), simultaneously with changes in the peripheral nervous system (Jayasinghe et al, 2012). In addition, bullous dermatitis and other rare manifestations are also observed (Dong et al, 2013).…”

Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research

“…Since, there are limited data about the hepatotoxicity of OPs in humans, it is not certain whether changes in biochemical parameters indicate actual liver damage. (90)(91)(92)(93)(94), energy production (93,(95)(96)(97), and cell death (98)(99)(100). Several studies have found an association between mitochondrial dynamics and malathion-induced drop in mitochondrial ATP synthesis in rat liver (9) or quinalphos and acephate effects on liver succinic dehydrogenase (84,85,101) and ATPase activities (87) -all of them the key enzymes for oxidative phosphorylation.…”

“…Several studies have evidenced the involvement of mitochondria in hepatotoxicity induced by OPs. For example, acute exposure to malathion and chronic exposure to dichlorvos and chlorpyrifos can increase the release of cytochrome C from mitochondria to cytosol and activate caspase-3 by disrupting cellular antioxidant defences (88,99,142). Diazinon can trigger apoptotic pathways by activating caspase-9 and caspase-3, increase the Bax/Bcl-2 ratio and protein disulphide isomerase (with pro-apoptotic function), and suppress endoplasmic Karami (81,143).…”

Malathion-induced testicular toxicity is associated with spermatogenic apoptosis and alterations in testicular enzymes and hormone levels in male Wistar rats

“…Residents near the farms and farmworkers may be [Machera et al, 2003], and dermal contact with contaminated soil and plants and from accidental spills [Tuomainen et al, 2002]. Acute exposure to OP insecticides and subsequent OP poisoning with muscle dysfunction can be a cause of deaths in humans due to mitochondrial dysfunction [Karami-Mohajeri et al, 2014]. Long term exposure to OP pesticides has been proved to impose higher risks of various chronic diseases [Mostafalou and Abdollahi, 2013].…”