Alirocumab in Dexamethasone-Induced Metabolic Syndrome: Therapeutic Benefits and Potential Hepatic Risks through RXR-α / p-AKT Modulation

Authors

• Miad A. Aljuhani, 1Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi ArabiaFollow
• Mohamed S. Abdel-Bakky, Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia

Keywords

Metabolic Syndrome X; Dexamethasone; Hepatotoxicity Aliro-cumab; RXR-α and p-AKT

Document Type

Research Article

Abstract

Background: Metabolic syndrome (MetS) elevates the risk of developing cardi-ovascular diseases and type 2 diabetes., driven by insulin resistance (IR), inflammation, and metabolic dysregulation. The PI3K/AKT pathway shows a key part in glucose and lipid metabolism. Alirocumab, a PCSK9 inhibitor, lowers LDL-C and improves IR but may cause hepatotoxicity. Aims: This study examines ali-rocumab’s effects on dexamethasone-induced MetS in rats, focusing on its metabolic benefits and potential liver toxicity. Methods: Over 30 days, 40 male Albino rats were distributed into control, Alirocumab, Dexamethasone, and Dexa-methasone+Alirocumab groups, with the latter receiving Dexamethasone to induce metabolic syndrome followed by Alirocumab administration. Results: Dex-amethasone significantly reduced body weight and HDL-C while increasing insulin, glucose, insulin resistance, and cholesterol levels. Alirocumab mitigated dexamethasone-induced dyslipidemia, lowering LDL-C and total cholesterol. However, it elevated ALT and AST levels, suggesting potential hepatotoxicity. Reactive oxygen species and inflammatory markers (IL-4, IL-6) increased with alirocumab and dexamethasone. Histopathological analysis revealed immune cell migration and decreased RXR-α with increase in p-AKT expression in Dexame-thasone group. A significant rise in RXR-α and p-AKT expressions were observed in the Dexamethasone/Alirocumab group compared to the Dexamethasone group. These findings indicate that alirocumab may counteract dexamethasone-induced metabolic syndrome but has liver-related effects. Conclusions: Aliro-cumab mitigates dexamethasone-induced metabolic syndrome by improving lipid profile and insulin sensitivity; however, its use is associated with elevated hepatic enzyme levels and altered RXR-α and p-AKT expression, indicating potential hepatotoxic effects.

Publisher

Saudi Toxicology Society

Recommended Citation

Aljuhani, Miad A. and Abdel-Bakky, Mohamed S. (2025) "Alirocumab in Dexamethasone-Induced Metabolic Syndrome: Therapeutic Benefits and Potential Hepatic Risks through RXR-α / p-AKT Modulation," Saudi Toxicology Journal: Vol. 2: Iss. 3, Article 1.
DOI: https://doi.org/10.70957/uqu.edu.sa/s.toxicology.s/stj.2025.1.3.1
Available at: https://stj.researchcommons.org/journal/vol2/iss3/1

DOI

https://doi.org/10.70957/uqu.edu.sa/s.toxicology.s/stj.2025.1.3.1