Potential Mechanisms of Imidacloprid-Induced Neurotoxicity in Adult Rats with Attempts on Protection Using Origanum majorana L. Oil/Extract: In Vivo and In Silico Studies

Abstract

Imidacloprid (IMI) insecticide is rapidly metabolized in mammals and contributes to neurotoxicity via the blocking of nicotinic acetylcholine receptors, as in insects. Origanum majorana retains its great antioxidant potential in both fresh and dry forms. No data is available on the neuroprotective effect of this plant in laboratory animals. In this context, aerial parts of O. majorana were used to prepare the essential oil (OMO) and methanol extract (OME). The potential neuroprotective impact of both OMO and OME against IMI-induced neurotoxicity in rats was explored. Forty-two rats were divided into 6 groups, with 7 rats in each one. Rats were daily administered the oral treatments: normal saline, OMO, OME, IMI, IMI + OMO, and IMI + OME. Our results revealed the identification of 55 components in O. majorana essential oil, most belonging to the oxygenated and hydrocarbon monoterpenoid group. Moreover, 37 constituents were identified in the methanol extract, mostly phenolics. The potent neurotoxic effect of IMI on rats was confirmed by neurobehavioral and neuropathological alterations and a reduction of both acetylcholine esterase (AchE) activity and dopamine (DA), serotonin (5HT), and γ-aminobutyric acid (GABA) levels in the brain. Exposure of rats to IMI elevates the malondialdehyde (MDA) levels and reduces the antioxidant capacity. IMI could upregulate the transcription levels of nuclear factor-κB (NF-κB), interleukin-1 β (IL-1β), and tumor necrosis factor (TNF-α) genes and express strong caspase-3 and inducible nitric oxide synthase (iNOS) immunostaining in most examined brain areas. On the other hand, rats coadministered OMO or OME with IMI showed a marked improvement in all of the studied toxicological parameters. In conclusion, cotreatment of O. majorana extracts with IMI can protect against IMI neurotoxicity via their potent antioxidant, anti-inflammatory, and anti-apoptotic effects. Thus, we recommend a daily intake of O. majorana to protect against insecticide’s oxidative stress-mediated neuroinflammatory stress and apoptosis. The molecular docking study of linalool, rosmarinic acid, γ-terpene, and terpene-4-ol justify the observed normalization of the elevated iNOS and TNF-α levels induced after exposure to IMI.

Oculomotor nerve palsy caused by imidacloprid at initial diagnosis: A case report

“…Regarding the neurotoxicity of pyraclostrobin, researchers have found that it can induce neurotoxicity in rats by blocking acetylcholinesterase activity and reducing dopamine, serotonin, and γ-aminobutyric acid levels. [ 14 ] Furthermore, pyraclostrobin elevates malondialdehyde levels and impairs antioxidant capacity, upregulates the transcription levels of nuclear factor-κB, interleukin-1β, and tumor necrosis factor genes, and expresses high caspase-3 and inducible nitric oxide synthase. This study also shows that essential oil from Origanum vulgare and its extracts can counteract the neurotoxicity of pyraclostrobin, preventing its neurotoxic effects through their potent antioxidant, anti-inflammatory, and antiapoptotic properties.…”

“…This study also shows that essential oil from Origanum vulgare and its extracts can counteract the neurotoxicity of pyraclostrobin, preventing its neurotoxic effects through their potent antioxidant, anti-inflammatory, and antiapoptotic properties. [ 14 ] A research team employed untargeted lipidomics and metabolomics techniques to uncover a new mechanism by which pyraclostrobin and another neonicotinoid insecticide, dinotefuran, exert toxic effects on Neuro-2a neural cells. These insecticides disrupt various lipid and amino acid metabolisms within cells, leading to cellular dysfunction and affecting the body’s normal antioxidant and immune regulatory functions, thereby inducing various diseases and adverse reactions, including neural weakness.…”

Study on network pharmacology of Ginkgo biloba extract against ischaemic stroke mechanism and establishment of UPLC‐MS/MS methods for simultaneous determination of 19 main active components

“…67 TNF is a pro-inflammatory cytokine, which can not only attract macrophages but also activate the NF-κB signalling pathway and stimulate vascular cells to produce inflammatory cytokines. 68 TNF-α and IL-6 are highly expressed in patients with cerebral ischaemia, coronary heart disease, angina pectoris, and other cardiovascular and cerebrovascular diseases, so reducing the levels of TNF-α and IL-6 is a great significance in the prevention of cardiovascular and cerebrovascular diseases. 69 Studies have also showed that ginkgo flavonoids can protect neurons from ischaemia/reperfusion (I/R) injury by inhibiting the NF-κB signalling pathway and downregulating pro-inflammatory cytokines.…”

“…AKT1 also had the function of regulating inflammatory response, and the activation of AKT1 may participate in neuroprotection against IS brain injury by inhibiting the JNK3 signalling pathway 67 . TNF is a pro‐inflammatory cytokine, which can not only attract macrophages but also activate the NF‐κB signalling pathway and stimulate vascular cells to produce inflammatory cytokines 68 . TNF‐α and IL‐6 are highly expressed in patients with cerebral ischaemia, coronary heart disease, angina pectoris, and other cardiovascular and cerebrovascular diseases, so reducing the levels of TNF‐α and IL‐6 is a great significance in the prevention of cardiovascular and cerebrovascular diseases 69 .…”

Chitosan nanoparticle encapsulation increased the prophylactic efficacy of Lactobacillus plantarum RM1 against AFM1-induced hepatorenal toxicity in rats

“…AFM 1 -induced ROS generation, as previously discussed, increases the permeability of the mitochondrial membrane and opens the transition pores, resulting in cytochrome c release to the cytosol, which initiates activation of caspase cascade ends with caspase-3 activation (Mariod et al 2023 ; Jabbar et al 2023b ). The caspase-3 is a protein member of the cysteine-aspartic acid protease family and is the end product of caspase activation (Hassanen et al 2023a ). It has an important role in the execution phase of programmed cell death.…”