Research Article Mohamed S. Othman*, Sofian T. Obeidat, Ghada M. Aleid, Mohamed M. Abdel-Daim, Ola A. Habotta, Laurent Schwartz, Amal H. Al-Bagawi, Manal M. Hussein, Ashraf Bakkar Pergularia tomentosa coupled with selenium nanoparticles salvaged lead acetate-induced redox imbalance, inflammation, apoptosis, and disruption of neurotransmission in rats’ brain https://doi.org/10.1515/chem-2022-0246 received September 19, 2022; accepted November 1, 2022 Abstract: In this study, the neuroprotective potential of either Pergularia tomentosa leaf methanolic extract (PtE) alone or in combination with selenium nanoparticles (SeNPs-PtE) was investigated against lead acetate (PbAc)- induced neurotoxicity. Experimental rats were pretreated with PtE (100 mg/kg) or SeNPs-PtE (0.5 mg/kg) and injected intraperitoneally with PbAc (20 mg/kg) for 2 weeks. Notably, SeNPs-PtE decreased brain Pb accumulation and enhanced the level of dopamine and the activity of AChE compared to the control rats. In addition, elevated neural levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione along with decreased lipid peroxidation levels were noticed in pretreated groups with SeNPs-PtE. Moreover, SeNPs-PtE significantly sup- pressed neural inflammation, as indicated by lower levels of interleukin-1 beta, interleukin-6, tumor necrosis factor- alpha, nuclear factor-kappa B p65, and nitric oxide in the examined brain tissue. The molecular results also unveiled significant down-regulation in iNOS gene expression in the brains of SeNPs-PtE-treated rats. In addition, SeNPs- PtE administration counteracted the neural loss by increasing B-cell lymphoma 2 (Bcl -2) and brain-derived neurotrophic factor levels as well as decreasing BCL2-associated X protein and caspase-3 levels. To sum up, our data suggest that P. tomentosa extract alone or in combination with SeNPs has great potential in reversing the neural tissue impairment induced by PbAc via its antioxidant, anti -inflammatory, and anti-apoptotic activities. This study might have therapeutic implications in preventing and treating several lead-induced neurological disorders. Keywords: Pergularia tomentosa, selenium nanoparticles, lead acetate, oxidative stress, neuroinflammation, apoptosis 1 Introduction Lead is a non-biodegradable environmental pollutant that has a wide range of harmful effects, particularly on brain-related disorders [1,2]. It is extensively found in the environment as it is used in pesticides, fertilizers, lead-containing gasoline, lead paints, cosmetics, and metal products as plumbing pipes [3]. The exposure of humans to lead may be occupational or through inges- tion of drinking water, and also environmental through traffic pollution, coal burning, or high lead levels in some regions [2]. According to the Institute for Health Metrics and Evaluation, lead exposure was responsible for nearly one million mortalities in 2017 [3]. Lead can also accumulate and cause damage to various organs, such as the brain, kidney, liver, heart, and immune system [4].  * Corresponding author: Mohamed S. Othman, Basic Sciences Department, University of Ha’il, 2240, Hail, Saudi Arabia, e-mail: biostar55@yahoo.com Sofian T. Obeidat, Ghada M. Aleid: Basic Sciences Department, University of Ha’il, 2240, Hail, Saudi Arabia Mohamed M. Abdel-Daim: Department of Pharmaceutical Sciences, Phamacy Program, Batterjee Medical College, 6231 Jeddah, Saudi Arabia; Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, 41522 Ismailia, Egypt Ola A. Habotta: Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, 35516, Mansoura, Egypt Laurent Schwartz: Oncology Department, Assistance Publique des Hopitaux de Paris, 71150 Paris, France Amal H. Al-Bagawi: Chemistry Department, Faculty of Science, University of Ha’il, 2240, Hail, Saudi Arabia Manal M. Hussein: Zoology and Entomology Department, Faculty of Science, Helwan University, 11795, Cairo, Egypt Ashraf Bakkar: Biochemistry Department, Faculty of Biotechnology, October University for Modern Science and Arts (MSA), 12585 Giza, Egypt Open Chemistry 2022; 20: 1313–1326 Open Access. © 2022 the author(s), published by De Gruyter. This work is licensed under the Creative Commons Attribution 4.0 International License.