Dysregulation of Hepatic AMPK and SIRT-1 Expressions Mediates Aluminum Oxide Nanoparticles-Induced Hepatic Injury and Microangiopathy in Rats with Special Emphasis on Shape-Dependent Hepatotoxicity | ||
| Egyptian Journal of Veterinary Sciences | ||
| Articles in Press, Corrected Proof, Available Online from 22 September 2025 PDF (1.27 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/ejvs.2025.401975.2960 | ||
| Authors | ||
| Esraa Mahmoud Hegazy1; Mohamed Y. Mahmoud2; Faten Fathy Mohammed* 3; Magdy M. El-Mahdy1 | ||
| 1Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt. | ||
| 2Toxicology and Forensic Medicine Department, Faculty of Veterinary Medicine, Cairo University, Giza , Egypt | ||
| 3Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt & Department of Pathology, College of Veterinary Medicine, King Faisal University, AlAhsa, 31982, Saudi Arabia. | ||
| Abstract | ||
| Aluminum oxide (Al2O3) nanoparticles (NPCs) are widely used in various medical purposes, including drug delivery; thus, the safety evaluation of their toxicity is crucial. The present study aimed to evaluate the hepatotoxic potential of Al2O3 nanoparticles in rats and clarify the molecular pathways that mediate their effect. The oral intoxication of rats with two different shapes of Al2O3 NPCs (nanoparticles spheres-NPS) and nanoparticles rods-NPRs) were performed, the doses were 20 mg and 40 mg/kg b.w. daily for 2 months. At the end of the experimental period, blood and liver samples were collected to determine liver biochemical enzymes and oxidative stress markers, in addition to histopathological evaluation of the liver. The immunohistochemical characterization of AMPK and SIRT-1 was also investigated. Results revealed that Al2O3 NPCs induced a significant increase in hepatic enzymes and oxidative stress parameters in a dose-dependent manner, severe histopathological hepatic alterations, including macro- to microvesicular hepatic steatosis, hepatocellular necrosis, in addition to severe portal reactions characterized by microangiopathy with portal cholangiofibrosis. Downregulation of AMPK and SIRT-1 expression in hepatic parenchyma was evident. Conclusion: The present study confirmed that aluminum nanoparticles have hepatotoxic potential in rats through the induction of oxidative stress and the downregulation of AMPK and SIRT-1. | ||
| Keywords | ||
| Aluminum oxide; Nanoparticles; liver; Sirt-1; AMPK; rat | ||
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