Effects of Deltamethrin on striatum and hippocampus mitochondrial integrity and the protective role of Quercetin in rats

Abstract

The present work is to evaluate the neurotoxicity induced by pyrethroid insecticide "Deltamethrin" at 0.32 mg/kg/day in two main regions of the Wistar rat brain (hippocampus and striatum) and the protective effects of Quercetin at 10 mg/kg/day on this toxicity after 90 days of exposure. The assay of brain parameters showed that Deltamethrin caused a significant increase of mitochondrial metabolite level (proteins, lipids, and carbohydrates) and enzyme activity (glutathione S-transferase and superoxide dismutase); a decreased amount of mitochondrial glutathione level and catalase and glutathione peroxidase activities; and an increase of malondialdehyde (MDA) acid levels of the two regions. Furthermore, mitochondrial functional testing in the brains of treated rats exhibited a significant increase in permeability followed by a mitochondrial swelling. Instead, a statistically significant decrease in mitochondrial respiration (O consumption) was recorded in the striatum and hippocampus. Our study showed that the pesticide caused a significant increase of the cytochrome c amount correlated with activation of neuronal apoptosis mechanisms by the significant increase of caspase-3 of hippocampus and striatum. In particular, the results of behavioral tests (open field, classic maze tests of sucrose, and Morris water maze) have significant changes, namely bad behavior of the treated rats, affecting the level of anxiety, learning, and memory, and general motor activity has mainly been shown in treated rats. In addition, the histological cuts clearly confirm cerebral necrosis in the hippocampus and the striatum caused by the pesticide. They allow us to consider the necrotic areas, black spots, reduction, and denaturation of these brain regions in the treated rats. On the other hand, we have studied the protective effects against the neurotoxicity of Deltamethrin (DLM). In this context, after the gavage of Quercetin at the dose of 10 mg/kg/day, we have noticed an improvement in the entire parameters: mitochondrial enzyme, metabolic, histological, and behavioral parameters. This confirmed the improvement of preventive and curative effect of Quercetin against free radicals induced by the DLM.

Quercetin in Food: Possible Mechanisms of Its Effect on Memory

“…Oral administration of quercetin (10 mg/kg, 90 days) modified the effects of deltamethrin (DLM), a model of neurotoxicity, on the increase in permeability and mitochondrial swelling, mitochondrial metabolite levels (proteins, lipids, and carbohydrates), enzyme activity (glutathione S‐transferase [GST] and superoxide dismutase), amount of cytochrome c and caspase‐3, and MDA acid levels caused by DLM in the hippocampus and striatum of rats. Furthermore, the histological results confirmed the protective effects of quercetin on brain cells in the hippocampus and striatum (Gasmi et al., ).…”

Protective Effects of Pelargonium graveolens Essential Oil on Methomyl-Induced Oxidative Stress and Spatial Working Memory Impairment in Association with Histopathological Changes in the Hippocampus of Male Wistar Rats

“…Exposure to cholinesterase-inhibiting pesticides negatively affects memory and cognition ( Chen et al, 2012 ; Kapil et al, 2010 ). Other studies have demonstrated that memory disorders after exposure to pesticides is associated with morphological changes and oxidative damage in neurons of the hippocampus ( Gasmi et al, 2017 ; Brocardo, Pandolfo, Takahashi, Rodrigues, & Dafre, 2005 ).…”

Pyrethroid exposure and neurotoxicity: a mechanistic approach

“…Caspase-3 has a vital function in both extrinsic and intrinsic pathways of apoptosis (116,117). In a study by Gasmi et al (15), exposure to deltamethrin resulted in higher cytochrome c and caspase-3, followed by apoptosis, which confirmed mitochondrial damage (swelling and permeability).…”

“…The main concern about exposure to pyrethroids is the development of progressive neurodegenerative disorders (50). Due to its lipophilic nature, for example, deltamethrin can reach the brain in amounts that are probably toxic (15). Numerous investigations have indicated that it increases the risk of neurodegenerative diseases (51-54), as it inhibits nerve impulse by altering voltage-sensitive sodium channel kinetics and ligand-gated ion channels (GABA receptors, nicotinic acetylcholine receptors, and glutamate receptors) (14,54).…”

“…Pyrethroids can trigger apoptosis through ROS such as H 2 O 2 or OH • (38,75,114) and cytotoxins (77,115). Deltamethrin has been evidenced to induce apoptosis in the neuronal cells of the cerebral cortex, hippocampus, and striatum (15,29).…”