PLGA-Encapsulated Pterostilbene Mitigates Cadmium-Induced Nephrotoxicity in Rats by Modulating Oxidative Stress, Inflammation, and Apoptosis

Cadmium (Cd) is an environmentally pervasive toxic metal that accumulates in the kidney and promotes oxidative stress, inflammation, and apoptosis. This study evaluated the renoprotective effects of free pterostilbene (PTS) and PLGA-encapsulated PTS (PTS-PLGA) in male Sprague–Dawley rats with Cd-induced nephrotoxicity. Rats received CdCl2 (2 mg/kg/day, intraperitoneally) for 3 weeks and oral free PTS or PTS-PLGA at a nominal PTS-equivalent dose of 50 mg/kg/day. The formulation dose was calculated from encapsulation efficiency; however, systemic and renal PTS exposure were not measured. Renal function, kidney injury molecule-1 (Kim-1), oxidative stress, inflammatory, and apoptosis-related markers were assessed together with histopathological, ultrastructural, and immunohistochemical changes. Cd exposure impaired renal function and increased Kim-1, reactive oxygen species, malondialdehyde, protein carbonyls, 8-hydroxy-2′-deoxyguanosine, inflammatory mediators, caspase activities, Bax/Bcl-2 ratio, and p53 expression. These changes were accompanied by reduced antioxidant defenses and Nrf2/HO-1-related markers, as well as marked histological and ultrastructural injury. Both PTS formulations attenuated Cd-associated renal alterations. Under the present dosing conditions, PTS-PLGA was associated with greater improvement than free PTS across most endpoints. PLGA-encapsulated PTS therefore warrants further preclinical investigation as a potential approach to mitigate Cd-induced nephrotoxicity; pharmacokinetic, biodistribution, and empty-carrier control studies are needed to define the basis of the observed formulation-related differences.