Protective effects of Opuntia ficus-indica (L.) Mill flower extract against imidacloprid-induced hepatotoxicity: Modulation of oxidative stress, apoptosis, and Raf/MEK/ERK-related gene expression.

Imidacloprid (IMI), a widely used neonicotinoid insecticide, is associated with hepatotoxic effects. This study evaluated the protective potential of Opuntia ficus-indica (L.) Mill. flower extract against IMI-induced liver injury in rats. Animals were allocated into four groups: control, extract-treated, IMI-treated, and extract plus IMI. Hepatic damage was assessed using histopathology, biochemical oxidative stress markers, and gene expression analysis of apoptotic and Raf/MEK/ERK pathway markers. IMI exposure induced marked liver injury, oxidative stress, and apoptosis, while co-treatment with the extract significantly ameliorated histological alterations, reduced lipid peroxidation, and enhanced antioxidant enzyme activities. The extract downregulated pro-apoptotic genes and suppressed the expression of Raf, MEK, and ERK. Molecular docking demonstrated a strong binding affinity of a major extract constituent (CID:20393) to extracellular signal-regulated kinase. These findings indicate that O. ficus-indica flower extract mitigates IMI-induced hepatotoxicity through antioxidant, anti-apoptotic, and modulation of signaling pathways.