Chlorpyrifos- and Dichlorvos-Induced Oxidative and Neurogenic Damage Elicits Neuro-Cognitive Deficits and Increases Anxiety-Like Behavior in Wild-Type Rats

Abstract

The execution of agricultural activities on an industrial scale has led to indiscriminate deposition of toxic xenobiotics, including organophosphates, in the biome. This has led to intoxication characterized by deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to a combination of two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP), on neuro-cognitive performance and anxiety-like behaviors in rats. Thirty-two adult male Wistar rats (150–170 g) were randomly divided into four groups, orally exposed to normal saline (NS), DDVP (8.8 mg/kg), CPF (14.9 mg/kg), and DDVP + CPF for 14 consecutive days. On day 10 of exposure, anxiety-like behavior and amygdala-dependent fear learning were assessed using open field and elevated plus maze paradigms, respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following three training trials on days 11, 12, and 13. On day 15, the rats were euthanized, and their brains excised, with the hippocampus and amygdala removed. Five of these samples were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three were processed for histology (cresyl violet stain) and proliferative markers (Ki67 immunohistochemistry). Marked (p ≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p ≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damage are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.

Red Beetroot Extract Abrogates Chlorpyrifos-Induced Cortical Damage in Rats

“…Organophosphorus compounds are used for various military, household, and agricultural purposes to control and prevent different disease vectors such as flies, cockroaches, beetles, helminthes, cockroaches, termites, and corn rootworms [24]. Exposure to organophosphorus is strongly associated with the loss of cellular functions and the development of different diseases such as cardiovascular, renal, respiratory, and neurodegenerative disorders [25]. CPF is a wide-spectrum organophosphorus insecticide, and its indoor and outdoor uses cause several side effects to animals and humans [24].…”

“…Oxidative Medicine and Cellular Longevity metabolism, and its dysregulation causes different pathological conditions. CPF at different doses can inhibit AChE in different experimental models, leading to the accumulation of acetylcholine at synaptosomes and thus producing memory and learning impairments [7,25]. It has been demonstrated that CPF is able to inhibit AChE activity by enhancing the phosphorylation of its serine site [26].…”

“…CPF enhances the overproduction of ROS and consequently triggers polyunsaturated lipid5 peroxidation in the brain and other tissues [12]. The elevation in the production of NO has been observed in the brain tissue in response to CPF treatment [25]. This increase has been attributed to the overexpression of iNOS which potentiates the synthesis of NO in the brain tissue [44].…”

Chlorpyrifos and Dichlorvos in Combined Exposure Reveals Antagonistic Interaction to Freshwater Fish Mrigal, Cirrhinus mrigala

“…Hernández et al (2013) described that the pesticide mixture changes the toxicokinetics of the individual compounds, thus modifying their toxicity. Therefore, chemical interaction between two pesticides might be the reason for the antagonistic result (Imam et al 2018). Likewise, authors (Stepić et al 2013;Wang et al 2017) stated enhanced metabolization processes leading to faster excretion of metabolites, eventually resulting in decreased pesticide toxicity.…”

Repeated exposure to chlorpyrifos is associated with a dose-dependent chronic neurobehavioral deficit in adult rats

“…Another study reported that CPF (2.5-20 mg/kg from postnatal days 27 to 36) produced depression-like behavioral signs when assessed one week following the last CPF dose [37]. Cognitive deficits along with anxiety traits were noted on days 10 and 14 of a two-week CPF (14.9 mg/kg) exposure paradigm [38]. Another study on behavioral toxicity of repeated CPF exposures showed that CPF (18 mg/kg daily for 14 days or every other day for 30 days) leads to increased impulsivity and reductions in attention when assessed during and up to 30 days post exposure [39,40].…”