Mitochondrial dysfunction and organophosphorus compounds

Abstract

Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed.

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

“…As a primary site of cellular energy generation and oxygen consumption, mitochondrion is a likely target for OPs, which may explain their non-cholinergic toxicity (88,89). Recent research has focused on the possible roles of mitochondrial dysfunction in OP-induced toxicity through mitochondrial respiration rate, respiratory chain enzymes…”

“…The best course of action to counter OP liver and mitochondrial toxicity in acute, subacute, sub-chronic, or chronic exposure is therefore to use antioxidants (89,119,165,166). The choice of antioxidants is wide, but several have been evidenced as potent against OP toxicity, including selenium (167), N-acetylcysteine (NAC), pentoxifylline (PTX), and alpha-tocopherol.…”

The sarin-like organophosphorus agent bis(isopropyl methyl)phosphonate induces ER stress in human astrocytoma cells

“…Some recent studies showed that sarin and other OP compounds induce multiple toxicities in vivo and in vitro (Banks and Lein, 2012;Karami-Mohajeri and Abdollahi et al, 2013). Treatment with OP compounds caused insult to neuronal cells and induced neuronal DNA damage, lipid peroxidation, mitochondrial dysfunction, and the inflammatory response.…”