Enhanced Renoprotective Effects of Morin-Loaded PLGA Nanoparticles Against Arsenic-Induced Kidney Injury in Rats: Amelioration of Oxidative Stress, Inflammation, Fibrosis, and Apoptosis

Background/Objectives: Arsenic (ARS) exposure is a major cause of kidney injury, driven by oxidative stress, inflammation, fibrosis, and apoptosis. This study evaluated the renoprotective effects of morin (MOR) and morin-loaded PLGA nanoparticles (MOR–PGNPs) against ARS-induced nephrotoxicity in rats. Methods: Sixty male Sprague Dawley rats were randomly allocated into six groups (n = 10 per group). The control group received corn oil. The MOR group received MOR (100 mg/kg), and the MOR–PGNPs group received the same dose of MOR encapsulated in PLGA nanoparticles. ARS was administered at 10 mg/kg for 14 days. Co-treated groups received ARS together with either MOR or MOR–PGNPs, with a 28 min interval between administrations. Renal function markers (serum urea, creatinine, uric acid, renal KIM-1), oxidative stress and antioxidant parameters (Nrf2/HO-1, CAT, SOD, GPx, ROS, MDA), inflammatory mediators (TLR4/NF-κB, TNF-α, IL-6, IL-1β), fibrotic markers (TGF-β1, fibronectin), and apoptotic proteins (caspase-3, caspase-8, Bax, Bcl-2) were assessed, alongside histopathological and ultrastructural evaluations. Results: ARS exposure significantly impaired renal function, increased KIM-1, suppressed Nrf2/HO-1 signaling, reduced antioxidant enzyme activities, and elevated ROS and MDA levels. It also activated TLR4/NF-κB signaling, upregulated pro-inflammatory cytokines and fibrotic markers, and increased pro-apoptotic proteins while downregulating Bcl-2. MOR co-treatment partially ameliorated these alterations. MOR–PGNPs produced potentially enhanced protection, restoring kidney function markers, enhancing antioxidant defenses, and markedly attenuating inflammation, fibrosis, and apoptosis. Histopathological and ultrastructural analyses confirmed preservation of glomerular and tubular architecture, mitochondrial integrity, and minimal cytoplasmic vacuolization in the MOR–PGNPs group. Conclusions: MOR–PGNPs at 100 mg/kg effectively mitigated ARS-induced renal damage through antioxidant, anti-inflammatory, antifibrotic, and anti-apoptotic mechanisms, supporting PLGA-based morin nanoparticles as a promising and safe renoprotective strategy.