Nicardipine protects against gentamicin-induced nephrotoxicity: Potential involvement of IL-23R, NRF2, and Beclin-1 perturbation.

AIMS: Gentamicin (GNT) remains a cornerstone in the treatment of severe Gram-negative infections; however, its clinical utility is constrained by dose-limiting nephrotoxicity. Emerging evidence implicates nicardipine (NIC), a dihydropyridine calcium channel blocker, in renoprotection via mechanisms distinct from its canonical vascular effects. In this study, we delineate an unprecedented nephroprotective mechanism of NIC in the context of GNT-induced renal injury, with a particular focus on its capacity to modulate oxidative stress, inflammatory signaling, autophagic, and apoptotic pathways.

MATERIALS AND

METHODS

Experimental groups comprised control rats, GNT-treated rats, NIC-treated rats, and animals that received NIC + GNT. Renal function was rigorously evaluated through measuring serum creatinine and blood urea nitrogen (BUN), alongside a multidimensional analysis encompassing oxidative stress indices, inflammatory mediators, histopathological alterations, and expression profiles of apoptosis- and autophagy-associated proteins. Mechanistic interrogation centered on nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense; interleukin-23 receptor (IL-23R), a pivotal mediator of proinflammatory signaling; and Beclin-1, a crucial autophagy-related factor underlying NIC's renoprotective action.

KEY FINDINGS: Co-administration of NIC markedly ameliorated GNT-induced renal injury, as reflected by improved biochemical indices of kidney function, preservation of renal histoarchitecture, attenuation of caspase-3-mediated apoptosis, upregulation of NRF2-driven antioxidant responses, suppression of IL-23R-dependent inflammatory signaling, and modulation of Beclin-1-associated autophagic activity.

SIGNIFICANCE: These findings delineate a novel mechanistic axis by which NIC exerts coordinated antioxidant, anti-inflammatory, autophagic, and anti-apoptotic effects. This multifactorial cytoprotection highlights NIC's therapeutic potential for targeted intervention in aminoglycoside-induced nephrotoxicity.