Protective Role of Apigenin-PEGylated Chitosan Nanoparticles Against Pesticide Deltamethrin-Induced Liver Injury via...

The present investigation evaluated the liver-protective effect of apigenin encapsulated in PEGylated chitosan nanoparticles (APG-PCHNPs) against hepatotoxicity induced by pesticide deltamethrin (DLM) in rats. Sixty rats were randomly allocated into six groups: a control group, groups treated with APG (20 mg/kg BW) or APG-PCHNPs (20 mg/kg BW), a group exposed to DLM (5 mg/kg BW), and two combination treatment groups receiving DLM (5 mg/kg BW) plus either APG or APG-PCHNPs at 20 mg/kg BW for 35 days. DLM administration significantly decreased serum total protein and its fractions. Simultaneously, hepatic enzyme activities, C-reactive protein, and total bilirubin concentrations were significantly elevated. DLM exposure induced oxidative damage by lowering the activity of vital antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase, reducing levels of reduced glutathione, and elevating malondialdehyde as a marker of lipid peroxidation. The observed biochemical alterations coincided with a significant increase in the expression of the apoptotic genes Bax and caspase-3, while the expression of the anti-apoptotic gene Bcl-2 was markedly reduced. Additionally, the pro-inflammatory mediators nuclear factor kappa B, tumor necrosis factor alpha, interleukin-6, and DNA oxidative damage biomarkers (8-OHdG) were significantly elevated in the liver following exposure to DLM. APG-PCHNPs provided markedly better protection than crude APG against DLM-induced hepatic damage (p < 0.05). This was evidenced by restored liver enzyme levels, improved antioxidant enzyme activities, reduced liver inflammation, decreased oxidative stress-induced apoptosis, and the reversal of histological and ultra-structural damage, with outcomes nearly comparable to controls. Docking studies revealed a high affinity of APG for key proteins regulating antioxidant activity, apoptotic pathways, and inflammatory responses. In conclusion, APG-PCHNPs provided superior protection against DLM-induced liver injury by enhancing antioxidant defenses, suppressing NF-κB-mediated inflammation, and modulating Bcl-2/Bax/Caspase-3 signaling to prevent apoptosis, outperforming crude APG due to improved stability, solubility, and bioavailability.