synergistic neuroprotection effects of atropine and citric acid mitigate dichlorvos-induced neurotoxicity and oxidative stress

Background: dichlorvos (ddvp), an organophosphate, inhibits acetylcholinesterase, leading to acetylcholine accumulation and subsequent muscarinic receptor hyperstimulation. this disrupts normal electrochemical impulse transmission and redox homeostasis. atropine, a competitive muscarinic receptor antagonist, is the primary antidote for organophosphate poisoning, mitigating muscarinic hyperstimulation. concurrently, citric acid is recognized for its antioxidant properties and potential to combat oxidative stress. this study aimed to investigate the neurotoxic effects of ddvp, focusing on its oxido-inflammatory mechanisms and neurobehavioral implications. it also explored the potential therapeutic benefits of supplemental atropine and citric acid co-treatment. methods: sixty-four male wistar rats were divided into groups and treated with standard rat pellets and water ad libitum, ddvp alone, ddvp + atropine, ddvp + citric acid, or ddvp + atropine + citric acid. neurobehavioral profiles were assessed, and biochemical analyses were conducted to evaluate oxidative stress, inflammatory markers, and neurotransmitter parameters. results: ddvp exposure significantly decreased cholinergic activity, increased oxidative stress and inflammatory neurochemicals, and resulted in poor neurobehavioral outcomes. these detrimental effects were stabilized by co-treatment with citric acid and atropine. the antioxidant and anti-inflammatory capacities of citric acid significantly supplemented atropine's neuroprotective mechanisms, potentially preventing long-term sequelae.conclusion: ddvp ingestion leads to significant neurobehavioral dysfunction by disrupting cholinergic, monoaminergic, and oxido-inflammatory functions. supplementation with atropine and citric acid markedly improved neurobehavioral outcomes, largely attributed to the neuroprotective effects of citric acid. these findings suggest that antioxidant supplementation may offer considerable therapeutic advantages in cases of organophosphate poisoning.