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.