UNVEILING THE COMPARATIVE TOXICITY OF ACUTE VS. CHRONIC ZINC OXIDE NANOPARTICLE EXPOSURE IN ALBINO MICE KIDNEYS: EVIDENCE OF METABOLIC AND MOLECULAR DISRUPTION

Abstract

Zinc oxide nanoparticles (ZnONPs) are widely used in various industrial and biomedical applications; however, their potential health risks remain a growing concern. This study investigated the nephrotoxic effects of both acute and chronic ZnONPs exposure in male adult albino mice. Mice were intraperitoneally administered ZnONPs at a dose of 5 mg/kg body weight weekly for acute exposure (1 week) and twice weekly for chronic exposure (10 weeks). A glucose tolerance test (GTT) was performed to assess metabolic disruption. The results revealed that chronic ZnONPs administration impaired glucose tolerance, suggesting a diabetogenic effect. Moreover, ZnONPs significantly increased the expression of pro-inflammatory (NF-κB, TNF-α) and apoptotic (caspase-3) markers in renal tissues, with more pronounced effects observed under chronic exposure. Notably, a marked downregulation of the antioxidant protein Sirtuin-1 (SIRT1) was observed, particularly in chronically treated mice, indicating impaired redox homeostasis. Collectively, these findings demonstrate that ZnONPs induce renal toxicity through mechanisms involving inflammation, oxidative stress, and apoptosis, with severity increasing over time.