Interplay between Amiodarone and Statins: Experimental Evidence of Synergistic Hepatotoxicity

Hager Zaki Elghareb, Demonstrator in Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Egypt.Follow
Abdel-Motaal M. Fouda, Professor of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Egypt.
Mohamed Mahmoud Elhadidi, Professor of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Egypt.
Ahmed Abdel-Monem Elmetwally, Assistant Professor of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Egypt.

Corresponding Author

hager zaki mohammed elghareb

Subject Area

Pharmacology

Article Type

Original Study

Abstract

Background: Drug-induced liver injury (DILI) continues to be a main contributor to acute liver failure. So, this study aimed to investigate interactions between amiodarone and atorvastatin concerning hepatic safety, due to increasing clinical practice of their combination for optimal arrhythmia control. Methods: Forty male Sprague Dawley rats were randomly divided into four groups (10 in each group). Group 1 was control group receiving normal saline. Group 2 received Amiodarone-only \ (administered 30 mg/kg/day orally). Group 3 received Atorvastatin only (administered 10 mg/kg/day orally). Group 4 received combination of both amiodarone and atorvastatin in same previous doses. All drugs were dissolved in saline and administered orally daily for a duration of 8 weeks. At the end of the study, animals were euthanized, and blood and liver tissue samples were obtained for biochemical, histopathological, and molecular analyses. Results: Treatment of the rats with amiodarone resulted in a significant elevation in liver enzymes than atorvastatin group and controls, signifying hepatocellular damage. Histopathological score signified moderate damage. The combination group showed the most severe liver injury across all groups. Biochemically, liver enzymes levels were dramatically elevated, nearly 5 fold and 3.9-fold higher than control. Oxidative stress reached its peak, reflecting overwhelming lipid peroxidation. In terms of histopathology, this group showed the worst damage: H&E scores reached median of 3 (range 2–3), with extensive necrosis, dense inflammatory infiltrates, severe steatosis, and architectural distortion. Conclusion: Results showed that the concomitant administration of amiodarone and atorvastatin results in a significantly greater degree of hepatic injury than either drug alone.

Recommended Citation

Elghareb, Hager Zaki; Fouda, Abdel-Motaal M.; Elhadidi, Mohamed Mahmoud; and Elmetwally, Ahmed Abdel-Monem (2025) "Interplay between Amiodarone and Statins: Experimental Evidence of Synergistic Hepatotoxicity," Mansoura Medical Journal: Vol. 54 : Iss. 4 , Article 15.
Available at: https://doi.org/10.58775/2735-3990.1480