Chlorfenapyr (CFP) is a widely used pesticide associated with nephrotoxicity through
oxidative stress, inflammation, and mitochondrial dysfunction. This study investigated
the protective effects of limonene (LM) and its nano-liposomal formulation (LM-LNPs)
against CFP-induced renal injury in rats. Animals were divided into six groups—control,
LM, LM-LNPs, CFP, CFP + LM, and CFP + LM-LNPs—and treated orally for 30 days. CFP
exposure resulted in marked renal dysfunction, histopathological and ultrastructural damage,
suppression of the NRF2/HO-1/NQO1 antioxidant pathway, depletion of endogenous
antioxidants excessive generation of reactive oxygen and nitrogen species, lipid peroxidation
products, and DNA damage. These changes were accompanied by activation of
NF-κB/COX-2-mediated inflammation, mitochondrial respiratory impairment, disrupted
energy metabolism, and induction of apoptosis. Co-treatment with LM significantly ameliorated
these alterations, whereas LM-LNPs produced greater improvements in renal
function, tissue architecture, redox homeostasis, mitochondrial function, and inflammatory
and apoptotic signaling. Immunohistochemical analyses further confirmed enhanced NRF2
expression and reduced NF-κB immunoreactivity in LM-LNP-treated kidneys. Overall,
nano-liposomal delivery enhanced the renoprotective efficacy of limonene, highlighting its
potential as a therapeutic strategy against pesticide-induced kidney injury