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Exploring the link between pyrethroids exposure and dopaminergic degeneration through morphometric, immunofluorescence, and in-silico approaches: the therapeutic role of chitosan-encapsulated curcumin nanoparticles

Affiliation
Department of Pharmaceutical Sciences ,College of Pharmacy ,Princess Nourah bint Abdulrahman University ,Riyadh ,Saudi Arabia
Alotaibi, Badriyah S.;
Affiliation
Department of Forensic Medicine and Toxicology ,Faculty of Veterinary Medicine ,Zagazig University ,Zagazig ,Egypt
Abdel-Rahman Mohamed, Amany;
Affiliation
Department of Forensic Medicine and Toxicology ,Faculty of Veterinary Medicine ,Zagazig University ,Zagazig ,Egypt
Abd-Elhakim, Yasmina M.;
Affiliation
Department of Histology and Cytology ,Faculty of Veterinary Medicine ,Damanhour University ,Damanhour ,Egypt
Noreldin, Ahmed E.;
Affiliation
Cytology and Histology Department ,Faculty of Veterinary Medicine ,University of Sadat City ,Sadat City ,Egypt
Elhamouly, Moustafa;
Affiliation
Department of Pharmacology ,Faculty of Veterinary Medicine ,Zagazig University ,Zagazig ,Egypt
Khamis, Tarek;
Affiliation
Department of Biochemistry ,Faculty of Veterinary Medicine ,Damanhour University ,Damanhour ,Egypt
El-Far, Ali H.;
Affiliation
Department of Basic Health Sciences ,College of Medicine ,Princess Nourah bint Abdulrahman University ,Riyadh ,Saudi Arabia
Alosaimi, Manal E.;
Affiliation
Department of Anatomy ,Faculty of Medicine ,University of Jeddah ,Jeddah ,Saudi Arabia
Dahran, Naief;
Affiliation
Department of Biochemistry ,College of Science ,University of Jeddah ,Jeddah ,Saudi Arabia
Alqahtani, Leena S.;
Affiliation
School of Biosciences and Veterinary Medicine ,University of Camerino ,Matelica ,Italy
Nicotra, Mario;
Affiliation
Forensic Medicine and Clinical Toxicology Department ,Faculty of Medicine ,Mansoura University ,Mansoura ,Egypt
El-Gamal, Mohamed;
Affiliation
School of Biosciences and Veterinary Medicine ,University of Camerino ,Matelica ,Italy
Di Cerbo, Alessandro

Introduction: The synthetic pyrethroid derivative fenpropathrin (FNE), a commonly used insecticide, has been associated with various toxic effects in mammals, particularly neurotoxicity. The study addressed the hallmarks of the pathophysiology of Parkinson’s disease upon oral exposure to fenpropathrin (FNE), mainly the alteration of dopaminergic markers, oxidative stress, and molecular docking in rat models. In addition, the protective effect of curcumin-encapsulated chitosan nanoparticles (CRM-Chs-NPs) was also assessed. Methods: In a 60-day trial, 40 male Sprague Dawley rats were divided into 4 groups: Control, CRM-Chs-NPs (curcumin-encapsulated chitosan nanoparticles), FNE (15 mg/kg bw), and FNE + CRM-Chs-NPs. Results: FNE exposure induced reactive oxygen species generation, ATP production disruption, activation of inflammatory and apoptotic pathways, mitochondrial function and dynamics impairment, neurotransmitter level perturbation, and mitophagy promotion in rat brains. Molecular docking analysis revealed that FNE interacts with key binding sites of dopamine synthesis and transport proteins. On the other hand, CRM-Chs-NPs mitigated FNE’s toxic effects by enhancing mitochondrial dynamics, antioxidant activity, and ATP production and promoting anti-inflammatory and antiapoptotic responses. Conclusion: In summary, FNE appears to induce dopaminergic degeneration through various mechanisms, and CRM-Chs-NPs emerged as a potential therapeutic intervention for protecting the nervous tissue microenvironment.

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License Holder: Copyright © 2024 Alotaibi, Abdel-Rahman Mohamed, Abd-Elhakim, Noreldin, Elhamouly, Khamis, El-Far, Alosaimi, Dahran, Alqahtani, Nicotra, El-Gamal and Di Cerbo.

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