Ursolic acid methyl ester mitigates aluminum oxide nanoparticle-induced hematobiochemical, immune, and oxidative disturbances and modulates apoptosis-related gene expression in Oreochromis niloticus.

Aluminum oxide nanoparticles (AONPs) represent an emerging toxicological risk to aquatic animals, with potential adverse effects on fish health and productivity. This study assessed the efficiency of ursolic acid methyl ester (UME) in reducing AONPs toxicity in Nile tilapia (Oreochromis niloticus). Three hundred tilapia fish (11.50 ± 0.50 g) were classified into four groups (75 fish per group, five replicates per group, and 15 fish per replicate): control, UME (1.0 mg/L water), AONPs (10 mg/L water), and UME + AONPs groups, with a forty-day exposure duration. A basal diet was fed to all groups. Comprehensive assessments included hepatorenal function, lipid and protein profiles, stress biomarkers, immune responses, antioxidant status, and tissue histomorphology. Hematological parameters were improved by aquas exposure of UME, reversing AONPs-induced anemia, leukopenia, hypoproteinemia, and hyperlipidemia. It also mitigated the elevation of serum levels of glucose, cortisol, liver enzymes, and kidney injury markers as well as hepatic malondialdehyde caused by AONPs. Tissue antioxidant biomarkers (hepatic CAT, SOD, and GPx) and immunological indicators (lysozyme activity, complement factor 3, nitric oxide, phagocytic activity %, and NBT) were both significantly boosted by UME exposure. At the molecular level, UME downregulated apoptosis-related genes (caspase-3 and p53) and upregulated immune- and cytoprotective-related genes (ifn-α, il-10, ho-1, and keap-1). The histological examination of the liver, kidneys, and spleen showed that UME significantly corrected the degenerative alterations brought on by AONPs. These findings advocate that UME is a promising candidate for mitigating AONPs toxicity in O. niloticus.