Toxicological mechanisms of aluminum oxide nanoparticles: insights into cytotoxicity and cell cycle perturbations in Musca domestica

Abstract

The expanding use of aluminum oxide nanoparticles (Al₂O₃-NPs) across industrial applications necessitates evaluating their biological interactions and potential environmental risks. This study provides a comprehensive assessment of the cytotoxic, genotoxic, and molecular effects of Al₂O₃-NPs on Musca domestica larvae, a suitable model for nanoparticle-induced toxicity. Biochemical analyses showed significant elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities following exposure, indicating cellular damage. Flow cytometric analysis revealed marked alterations in cell cycle progression, including decreased G₀–G₁ phase populations and increased S, G₂–M, and pre-G₁ (apoptotic) fractions, reflecting DNA damage and cell cycle arrest. Complementary viability assays demonstrated substantial reductions in cell viability and increased early and late apoptosis, while necrosis remained minimal. Molecular docking indicated strong and selective binding of Al₂O₃-NPs to cytochrome P450, characterized by a stable hydrogen bond at SER410, suggesting preferential interactions with detoxification pathways. Correspondingly, several cytochrome P450 genes, particularly CYP6A36 and CYP6G4, were significantly upregulated, reflecting an adaptive detoxification response to nanoparticle-induced stress. Collectively, the findings demonstrate that Al₂O₃-NPs disrupt cellular homeostasis in insects through oxidative, apoptotic, and detoxification-mediated mechanisms, providing important insights into the mechanistic toxicology and environmental implications of aluminum-based nanomaterials. KEY WORDS: Al₂O₃-NPs, Cell cycle, Apoptosis, Molecular docking Bull. Chem. Soc. Ethiop. 2026, 40(11), 2489-2502 DOI: https://dx.doi.org/10.4314/bcse.v40i11.15