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 (IRE1,
XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-, IL-1), 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.