Malathion Neurotoxic Effects on Dopaminergic System in Mice: Role of Inflammation

Background: Pesticides exposure is considered a global health problem. Increased risk of neurodegenerative disorders has been strongly associated with chronic repeated exposure to organophosphates. The mechanism of chronic neurotoxicity is still unclear and seems to be different from cholinergic affection in acute toxicity.

Methods & Findings: This work aims to verify the degenerative effects of chronic malathion exposure on dopaminergic system in BALB/c mice and to identify the possible contributing mechanism. Behavioural tests were done to assess locomotor performance in malathion-treated mice. To evaluate the histopathological consequences in the mice brains, dopaminergic neurons in the substantia nigra were assessed by antibodies to tyrosine hydroxylase. Additionally, microglia and neuroinflammation were identified using Iba-1 immunostaining. We also investigated the role of dexamethasone (Dx) and acetyl salicylic acid (ASA) in ameliorating malathion neurotoxic effects. Results revealed that some neurobehavioural deficits were detected in malathion-treated mice. They were associated with decreased corpus striatum fiber density, increased dopaminergic neurodegeneration in substantia nigra and increased number of activated microglia. Treatment with ASA and Dx imparted significant protection against malathion neurotoxicity as evidenced by improved neurobehavioural performance and diminished neurodegeneration in the nigrostriatal system.

Conclusion: Our findings advocate the use of antiinflammatory drugs as possible neuroprotective therapy against organophosphates-induced neurodegeneration. It is recommended to perform longer studies to examine the complete reversibility of OPs-induced neurotoxicity in response to different anti-inflammatory agents (the exact doses and duration) and to extrapolate the findings to humans chronically exposed to malathion.


Dalia Ahmed, Rania Hamed Abdel-Rahman, Mohamed Salama, Laila M El-Zalabany and Mona,Ahmed El-Harouny

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