pH-Responsive Carboxymethyl Cellulose-Encapsulating Hesperidin-Selenium Nanoparticles Attenuate Paracetamol-Induced Acute Kidney Injury via Keap-1/Nrf2, NF-κB, and Mitochondrial Apoptosis Modulation
Abstract
Paracetamol overdose is a major cause of drug-induced acute kidney injury (AKI), driven by oxidative stress, inflammation, mitochondrial dysfunction, and tubular apoptosis. This study evaluated the nephroprotective efficacy of pH-responsive carboxymethyl cellulose-encapsulated hesperidin-stabilized selenium nanoparticles (CMC@HES-SeNPs) against paracetamol-induced AKI in rats. HES-SeNPs were synthesized using hesperidin as a reducing/stabilizing agent and further coated with CMC. The nanoparticles were characterized by DLS, zeta potential, TEM, and in vitro release kinetics at pH 7.4 and 5.5. 42 Male rats were allocated into groups of control, paracetamol (PAR), paracetamol treated with sodium selenite (PAR&Se), paracetamol treated with hesperidin (PAR&HES), paracetamol treated with hesperidin-loaded selenium nanoparticles (PAR&HES-SeNPs), and paracetamol treated with carboxy methyl cellulose-coated hesperidin-loaded selenium nanoparticles (PAR&CMC@HES-SeNPs). Paracetamol markedly impaired renal function, increasing creatinine, urea, NGAL, KIM-1, and cystatin-C, and induced oxidative/nitrosative stress, Keap-1 upregulation, Nrf2 suppression, NF-κB-mediated inflammation, cytochrome-C release, Bax/Bcl-2 imbalance, caspase-3 activation, and severe renal histopathological injury. CMC@HES-SeNPs displayed sustained, pH-enhanced hesperidin release and produced the strongest renoprotective response, restoring renal biomarkers, associated with restoration of Keap-1/Nrf2-related…
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