International Journal of Environmental Health Research, 2026 (SCI-Expanded, Scopus)
Gentamicin (GEN) is an effective aminoglycoside whose clinical use is limited by dose-dependent nephrotoxicity. This study evaluated renoprotective effects and mechanisms of zinc nanoparticles synthesized with an extract of the edible mushroom Boletus edulis (BE-ZnNPs). BE-ZnNPs were characterized by UV–Vis, FTIR, XRD and STEM. Thirty-five rats were divided into five groups: Control; GEN (100 mg/kg, i.p.); GEN +BE-ZnNPs (1 mg/kg, p.o.); GEN + BE-ZnNPs (3 mg/kg, p.o.); and BE-ZnNPs (3 mg/kg) alone. Biochemical (BUN, creatinine), molecular (qRT-PCR for Bax, Bcl-2, Casp-3, Cyt-c, Nrf2, HO-1, Hsp27, Hsp70), histopathological, and immunohistochemical (8-OHdG, 4-HNE, dityrosine, cleaved caspase-3) analyses were performed. GEN caused significant renal dysfunction, histological damage, and increased oxidative-stress and apoptosis markers. BE-ZnNPs treatment—particularly at 3 mg/kg—markedly improved BUN/creatinine and histology, reduced oxidative and apoptotic immunopositivity, upregulated Bcl-2, Nrf2, and HO-1, and downregulated Bax, Casp-3, Cyt-c, Hsp27, and Hsp70. Protection is mediated by activation of the Nrf2/HO-1 antioxidant pathway and inhibition of the intrinsic mitochondrial apoptotic cascade. BE-ZnNPs are a promising biocompatible agent to mitigate drug-induced kidney injury.