Methods
This study investigated the ACR-induced renal damage mechanisms, particularly focusing on the regulating role of miR-21a-5p/fibrotic and miR-122-5p/inflammatory signaling pathways via targeting Timp-3 and TP53 proteins in an In silico preliminary study. Besides, renal function assessment, oxidative status, protein profile, and the expression of renal biomarkers (Timp-1, Keap-1, Kim-1, P53, TNF-α, Bax, and Caspase3) were assessed in a 60-day experiment. The examination was additionally extended to explore the potential protective effects of green-synthesized zinc oxide nanoparticles (ZNO-MONPs). A four-group experiment including control, ZNO-MONPs (10 mg/kg b.wt.), ACR (20 mg/kg b.wt.), and ZNO-MONPs + ACR was established encompassing biochemical, histological, and molecular levels. The study further investigated the protein-binding ability of ZNO and MONPs to inactivate caspase-3, Keap-1, Kim-1, and TNFRS-1A.
Results
ZNO-MONPs significantly reduced ACR-induced renal tissue damage as evidenced by increased serum creatinine, uric acid, albumin, and oxidative stress markers. ACR-induced oxidative stress, apoptosis, and inflammationare revealed by biochemical tests, gene expression, and the presence of apoptotic nuclei microscopically. Also, molecular docking revealed binding affinity between ACR-BCL-2 and glutathione-synthetase, elucidating the potential mechanisms through which ACR induces renal damage. Notably, ZNO-MONPs revealed a protective potential against ACR-induced damage. Zn levels in the renal tissues of ACR-exposed rats were significantly restored in those treated with ACR + ZNO-MONPs. In