Role of IRE1α/XBP1/CHOP/NLRP3 Signalling Pathway in Neonicotinoid Imidacloprid-Induced Pancreatic Dysfunction in Rats and Antagonism of Lycopene: In Vivo and Molecular Docking Simulation Approaches
Walaa Bayoumie El Gazzar,
Heba Bayoumi,
Heba S. Youssef,
Tayseer A. Ibrahim,
Reham M. Abdelfatah,
Noha M. Gamil,
Mervat K. Iskandar,
Amal M. Abdel-Kareim,
Shaymaa M. Abdelrahman,
Mohammed A. Gebba,
Mona Atya Mohamed,
Maha M. Mokhtar,
Tayseir G. Kharboush,
Nervana M. Bayoumy,
Hatun A. Alomar,
Amina A. Farag
Affiliations
Walaa Bayoumie El Gazzar
Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan
Heba Bayoumi
Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt
Heba S. Youssef
Department of Physiology, Faculty of Medicine, Benha University, Benha 13518, Egypt
Tayseer A. Ibrahim
Department of Physiology, Faculty of Medicine, Benha University, Benha 13518, Egypt
Reham M. Abdelfatah
Department of Pesticides, Faculty of Agriculture, Mansoura University, Mansoura 35516, Egypt
Noha M. Gamil
Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City 12573, Egypt
Mervat K. Iskandar
Department of Zoology, Faculty of Science, Benha University, Benha 13518, Egypt
Amal M. Abdel-Kareim
Department of Zoology, Faculty of Science, Benha University, Benha 13518, Egypt
Shaymaa M. Abdelrahman
Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt
Mohammed A. Gebba
Department of Anatomy& Embryology, Faculty of Medicine, Benha University, Benha 13518, Egypt
Mona Atya Mohamed
Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt
Maha M. Mokhtar
Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, Egypt
Tayseir G. Kharboush
Department of Pharmacology and Therapeutics, Faculty of Medicine, Benha University, Benha 13518, Egypt
Nervana M. Bayoumy
Department of Physiology, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia
Hatun A. Alomar
Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Amina A. Farag
Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, Egypt
Imidacloprid (IMI) is a commonly used new-generation pesticide that has numerous harmful effects on non-targeted organisms, including animals. This study analysed both the adverse effects on the pancreas following oral consumption of imidacloprid neonicotinoids (45 mg/kg daily for 30 days) and the potential protective effects of lycopene (LYC) administration (10 mg/kg/day for 30 days) with IMI exposure in male Sprague–Dawley rats. The apoptotic, pyroptotic, inflammatory, oxidative stress, and endoplasmic reticulum stress biomarkers were evaluated, along with the histopathological alterations. Upon IMI administration, noticeable changes were observed in pancreatic histopathology. Additionally, elevated oxidative/endoplasmic reticulum-associated stress biomarkers, inflammatory, pyroptotic, and apoptotic biomarkers were also observed following IMI administration. LYC effectively reversed these alterations by reducing oxidative stress markers (e.g., MDA) and enhancing antioxidant enzymes (SOD, CAT). It downregulated ER stress markers (IRE1α, XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-α, IL-1β), and suppressed pyroptotic (NLRP3, caspase-1) along with apoptotic markers (Bax, cleaved caspase-3). It also improved the histopathological and ultrastructure alterations brought on by IMI toxicity.
