Imidacloprid Induces Neurotoxicity in Albino Male Rats by Inhibiting Acetylcholinesterase Activity, Altering Antioxidant Status, and Primary DNA Damage

Abstract

Imidacloprid (IMI) is a neonicotinoid insecticide used worldwide, either alone or in combination with other pesticides. The goal of this study was to assess the effects of IMI on the central nervous system of rats and its mechanism of oxidative stress-induced DNA damage by oxidant/antioxidant parameters. Fifteen male rats, divided into three groups, were used: the first group received 5 ml/kg body weight corn oil as a control, the second received a high oral dose of IMI (45 mg/kg body weight), while the third received a low dose (22 mg/kg body weight). After 28 days, acetylcholinesterase (AChE) activity, oxidative stress markers, histopathological alterations, and DNA damage were examined in the brains of these rats. The AChE activities decreased significantly after IMI exposure, reaching 2.45 and 2.75 nmol/min/mg protein in high dose and low dose, respectively, compared to the control group (3.75 nmol/g tissues), while the concentration of malondialdehyde MDA increased significantly (29.28 and 23.92 nmol/g tissues) vs. the control group (19.28 nmol/g tissues). The antioxidant status parameters such as reduced glutathione (GSH) content was 13.77 and 17.63 nmol/g, catalase (CAT) activity was 22.56 and 26.65 µmol/min/g, and superoxide dismutase (SOD) activity was 6.66 and 7.23 µmol/min/g in both doses against the control group (21.37 nmol/g, 30.67 µmol/min/g, 11.76 µmol/min/g), respectively, and histopathological changes in the brain tissues were observed. More in vivo research using epigenetic methods is needed to determine the ability of IMI and its metabolites to cause neurotoxicity and DNA lesions in mammalian brains.

Figure 1

Acetylcholinesterase activity in rat brain tissues after 28 days of oral IMI exposure. Values are expressed as the mean ± SD expressed as nmol of acetylthiocholine hydrolyzed per minute per mg protein. 45 mg/kg B.W., and 22.5 groups vs. control p < 0.05 three groups (n = 5).

Figure 2

Malondialdehyde levels in rat brain tissues after 28 days of oral IMI exposure. Values are expressed as the mean ± SD expressed as nmol of MDA per g protein. 45 mg/kg B.W., and 22.5 groups vs. control p < 0.05 three groups (n = 5).

Figure 3

Reduced glutathione content in rat brain tissues after 28 days of oral IMI exposure. Values are expressed as the mean ± SD expressed as mmol of g tissues. 45 mg/kg B.W., and 22.5 groups vs. control p < 0.05 three groups (n = 5).

Figure 4

Catalase levels in rat brain tissues after 28 days of oral IMI exposure. Values are expressed as the mean ± SD expressed as units of CAT per g protein. 45 mg/kg B.W., and 22.5 groups vs. control p < 0.05 three groups (n = 5).

Figure 5

Superoxide dismutase levels in rat brain tissues after 28 days of oral IMI exposure. Values are expressed as the mean ± SD expressed as units of SOD per g protein. 45 mg/kg B.W., and 22.5 groups vs. control p < 0.05 three groups (n = 5).

Figure 6

Agarose gel electrophoresis was used to evaluate the fragmentation of rat brain DNA in all experimental groups. Ladder DNA marker, DNA patterns of the control group, the treated group (low dose), and the treated group (high dose).

Figure 7

Displayed a photomicrograph of the cerebral cortex, subiculum, fasci dentata and hilus, straitum, and cerebellum in rat brain tissues for histopathological extermination in a control group.

Figure 8

Displayed a photomicrograph of the cerebral cortex, subiculum, fasci dentata and hilus, straitum, and cerebellum in rat brain tissues for histopathological changes in a low dose group.

Figure 9

Displayed a photomicrograph of the cerebral cortex, subiculum, fasci dentata and hilus, straitum, and cerebellum in rat brain tissues for histopathological changes in a high dose group.