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.

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-1ß), 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.

Berberine chloride loaded nano-PEGylated liposomes attenuates imidacloprid-induced neurotoxicity by inhibiting NLRP3/Caspase-1/GSDMD-mediated pyroptosis.

Concerns have been expressed about imidacloprid (IMI), one of the most often used pesticides, and its potential neurotoxicity to non-target organisms. Chronic neuroinflammation is central to the pathology of several neurodegenerative disorders. Hence, exploring the molecular mechanism by which IMI would trigger neuroinflammation is particularly important. This study examined the neurotoxic effects of oral administration of IMI (45 mg/kg/day for 30 days) and the potential neuroprotective effect of berberine (Ber) chloride loaded nano-PEGylated liposomes (Ber-Lip) (10 mg/kg, intravenously every other day for 30 days) using laboratory rat. The histopathological changes, anti-oxidant and oxidative stress markers (GSH, SOD, and MDA), proinflammatory cytokines (IL1ß and TNF-α), microglia phenotype markers (CD86 and iNOS for M1; CD163 for M2), the canonical pyroptotic pathway markers (NLRP3, caspase-1, GSDMD, and IL-18) and Alzheimer's disease markers (Neprilysin and beta amyloid [Aß] deposits) were assessed. Oral administration of IMI resulted in apparent cerebellar histopathological alterations, oxidative stress, predominance of M1 microglia phenotype, significantly upregulated NLRP3, caspase-1, GSDMD, IL-18 and Aß deposits and significantly decreased Neprilysin expression. Berberine reduced the IMI-induced aberrations in the measured parameters and improved the IMI-induced histopathological and ultrastructure alterations brought on by IMI. This study highlights the IMI neurotoxic effect and its potential contribution to the development of Alzheimer's disease and displayed the neuroprotective effect of Ber-Lip.