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