Luteolin‐Loaded Chitosan Nanoparticles Attenuate Fenvalerate‐Induced Nephrotoxicity and Humoral Immune Suppression via NRF2/HO‐1 Activation and NF‐κB‐Mediated Inflammatory and Apoptotic Pathway Inhibition

Fenvalerate (FEV), a widely used pyrethroid, induces renal toxicity and suppresses humoral immunity. This study evaluated the protective effects of crude luteolin (LUT) and LUT-loaded chitosan nanoparticles (LUT-CHNPs) in male Wistar rats. The research included 60 rats divided into six groups: control, LUT, LUT-CHNPs, FEV, FEV + LUT, and FEV + LUT-CHNPs and administered oral treatment for a duration of 30 days. Exposure to FEV elevated levels of renal biomarkers, oxidative stress markers, pro-inflammatory cytokines, apoptotic proteins, and complement C3. It also reduced levels of antioxidant enzymes, GSH, NRF2/HO-1 expression, Bcl-2, and immunoglobulins (IgG, IgM). The concurrent administration of LUT-CHNPs significantly enhanced these alterations, restoring renal function, oxidative balance, anti-inflammatory and anti-apoptotic mechanisms, and humoral immunity. Histopathological and ultrastructural analyses confirmed the preservation of glomerular and tubular architecture, mitochondrial integrity, and organization of apical microvilli with LUT-CHNPs, indicating superior efficacy relative to crude LUT. The findings indicate that LUT-CHNPs enhance drug bioavailability and safeguard the kidneys and immune system against FEV-induced nephrotoxicity and immune suppression.