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

Eman I Hassanen; Marwa Y Issa; Neven H Hassan; Marwa A Ibrahim; Iten M Fawzy; Sherif Ashraf Fahmy; Sally Mehanna

doi:10.1021/acsomega.2c08295

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

ACS Omega. 2023 May 17;8(21):18491-18508. doi: 10.1021/acsomega.2c08295. eCollection 2023 May 30.

Authors

Eman I Hassanen¹, Marwa Y Issa², Neven H Hassan³, Marwa A Ibrahim⁴, Iten M Fawzy⁵, Sherif Ashraf Fahmy⁶, Sally Mehanna⁷

Affiliations

¹ Department of Pathology, Faculty of Veterinary Medicine, Cairo University, 12211 Giza, Egypt.
² Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, 11562 Cairo, Egypt.
³ Department of Physiology, Faculty of Veterinary Medicine, Cairo University, 12211 Giza, Egypt.
⁴ Department of Biochemistry, Faculty of Veterinary Medicine, Cairo University, 12211 Giza, Egypt.
⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Future University in Egypt, 11835 Cairo, Egypt.
⁶ Department of Chemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative Capital, 11835 Cairo, Egypt.
⁷ Department of Animal Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, 12211 Giza, Egypt.

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.