Mentha-mediated selenium nanoparticles attenuate adriamycin-induced chronic kidney disease via multi-target modulation of oxidative, inflammatory, and fibrotic pathways.

BACKGROUND: Chronic kidney disease (CKD) is characterized by progressive renal dysfunction associated with oxidative stress, inflammation, apoptosis, podocyte injury, and fibrotic remodeling. Adriamycin (ADR)-induced nephropathy is a widely used experimental model that reproduces key features of CKD, including proteinuria, glomerular and tubular injury, and renal fibrosis. Green-synthesized selenium nanoparticles (SeNPs) have emerged as potential renoprotective agents owing to their antioxidant activity and favorable biocompatibility.

OBJECTIVE: This study investigated the renoprotective efficacy of Mentha-mediated biosynthesized SeNPs against ADR-induced CKD in rats and explored the underlying molecular mechanisms.

METHODS: SeNPs were biosynthesized using sodium selenite and Mentha extract as reducing and capping agent. The synthesized nanoparticles were characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), zeta size and zeta potential analysis, X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). Eighteen male Sprague-Dawley rats were allocated into control, ADR-induced CKD, and ADR + SeNPs groups. At the end of the experimental period, renal function markers, oxidative stress parameters, proteinuria, histopathological alterations, alpha smooth muscle actin (α-SMA) immunoreactivity, and the mRNA expression of apoptotic, inflammatory, and fibrotic genes were assessed.

RESULTS: Characterization confirmed the formation of predominantly spherical SeNPs with a primary particle size of approximately 45-50 nm, a crystalline trigonal selenium structure, moderate colloidal stability, and surface functional groups consistent with biological capping. ADR administration caused significant renal dysfunction, increased urinary protein-to-creatinine ratio (UPCR), decreased renal Wilms tumor 1 (WT1) protein concentration, increased malondialdehyde (MDA), reduced superoxide dismutase (SOD) activity, severe histopathological damage. ADR also increased collagen deposition and α-SMA immunoreactivity and upregulation of Bax, p53, TNF-α, TGF-β, and Collagen-1 genes. SeNPs treatment improved serum renal-function parameters, significantly reduced UPCR, increased renal WT1 concentration, restored SOD activity, decreased MDA levels, and restored renal histoarchitecture. SeNPs also reduced α-SMA immunoreactivity, attenuated fibrotic alterations, and downregulated pro-apoptotic, pro-inflammatory, and pro-fibrotic gene expressions.

CONCLUSION: Mentha-derived SeNPs effectively attenuated ADR-induced CKD through coordinated antioxidant, anti-inflammatory, anti-apoptotic, and anti-fibrotic actions. These findings highlight the therapeutic potential of green-synthesized SeNPs as a promising nano-based therapeutic approach for chronic renal injury.