Hepatotoxic Effects of an Oral Amiodarone in White Albino Rats: Sub-Acute Biochemical, and Histopathological Assessments

Alzahraa Fatima Safa'a Fadhil; Yasir Mustafa kamal; Huda jaber waheed; Medhat ismail

doi:10.32947/ajps.v24i3.1058

Authors

Alzahraa Fatima Safa'a Fadhil Pharmacology and Toxicology department, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
Yasir Mustafa kamal Pharmacology and Toxicology department, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
Huda jaber waheed Pharmacology and Toxicology department, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
Medhat ismail Department of pharmacology faculty of medicine, Azhar University, Cairo, Egypt

DOI:

https://doi.org/10.32947/ajps.v24i3.1058

Keywords:

amiodarone, hepatotoxicity, phospholipidosis

Abstract

Amiodarone, potent antidysrhythmic, widely used drug that has been associated with hepatic toxicity in long-term or excessive use. In the presented study twelve rats were allocated into two groups and given daily doses via gastric gavage orally for two weeks as follows;

The first group served as a control normal group, whereas the second got amiodarone at a dosage of 300mg/kg/day orally. Liver tissues were processed for light microscopy, and blood samples were examined for serum transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and phospholipase a2 enzyme (Pla2) (which are thought to be an indicator of phospholipidosis and lipid buildup). Amiodarone was shown to produce hepatic histological abnormalities such as blood vessel congestion, leucocytic infiltration, liver degeneration, and stages of steatosis and necrosis of hepatocytes. The biochemical assessments were revealed that there was an elevation in amiodarone group's ALT and AST levels as a result of hepatic necrosis leading to leakage of enzymes content, while serum Pla2 was lowered significantly. Also, histopathology indicates stages of steatosis (Lipid accumulation) in hepatocytes, which may lead to farther damage in the late stages of hepatotoxicity.

References

- Sarah SH, Yassir MK, Huda JW. Astaxanthin effect on apoptotic biomarkers in methotrexate-induced liver injury Al Mustansiriyah J Pharm Sci. 2022; 10(24): 43-50.

- Inam SA, Israa R, Hayder L. Nuclear Factor Erythroid-2 Linked Factor (Nrf2) as a Potential Mediator of Hepatotoxicity Al Mustansiriyah J Pharm Sci. 2022; 4(19):12-16.

- LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012.

- Biancatelli RMC, Congedo V, Calvosa L, Ciacciarelli M, Polidoro A, Iuliano L. Adverse reactions of Amiodarone. Journal of geriatric cardiology: JGC, (2019); 16(7), 552.‏

- Dragovic S, Vermeulen NP, Gerets HH, Hewitt PG, Ingelman‐Sundberg M, Park BK, Weaver RJ. Evidence-based selection of training compounds for use in the mechanism-based integrated prediction of drug-induced liver injury in man. Archives of toxicology, (2016); 90, 2979-3003.‏

- Hussain N, Bhattacharyya A, Prueksaritanond S. Amiodarone-induced cirrhosis of liver: what predicts mortality? International Scholarly Research Notices, 2013.‏

- Nasser M, Larsen TR, Waanbah B, Sidiqi I, McCullough PA. Hyperacute drug-induced hepatitis with intravenous amiodarone: case report and review of the literature. Drug, healthcare and patient safety, (2013); 191-198.‏

- Gluck N, Fried M, Porat R. Acute amiodarone liver toxicity likely due to ischemic hepatitis. Isr Med Assoc J. 2011; 13:748–752.

- Kim G, Choi HK, Lee H, Moon KS, Oh JH, Lee J, Kim DH. Increased hepatic acylcarnitines after oral administration of amiodarone in rats. Journal of Applied Toxicology, (2020); 40(7), 1004-1013.‏

- Aldrich S. Aspartate Aminotransferase (AST) Activity Assay Kit. 2017;1– 4

- Aldrich S. Alanine Aminotransferase Activity Assay Kit. 2017; 1–4.

- SAS.2010.SAS/STAT Users Guide for Personal Computer. Release 9.13.SAS Institute, Inc., Cary, N.C., USA.

- Fonseca P, Dias A, Gonçalves H, Albuquerque A, Gama V. Acute hepatitis after amiodarone infusion. World J. Clin. Cases, 2015; 3(10):900.

- Riaz H, Saleem N, Ahmad M, Mehmood Y, Raza SA, Khan S, Kamran SH. Hepatoprotective effect of Crocus sativus on amiodarone-induced liver toxicity. Br. J. Pharm. Res, (2016); 12(4), 1-11.‏

- Vitins AP, Kienhuis AS, Speksnijder EN, Roodbergen M, Luijten M, van der Ven LTM. Mechanisms of amiodarone and valproic acid induced liver steatosis in mouse in vivo act as a template for other hepatotoxicity models. Arch Toxicol, 2014; 88: 1573–1588.

- Sagini K, Buratta S, Delo F, Pellegrino RM, Giovagnoli S, Urbanelli L, Emiliani C. Drug-induced lysosomal impairment is associated with the release of extracellular vesicles carrying autophagy markers. International Journal of Molecular Sciences, (2021); 22(23), 12922.‏

- Hinkovska-Galcheva V, Treadwell T, Shillingford JM, Lee A, Abe A, Tesmer JJ, & Shayman JA. Inhibition of lysosomal phospholipase A2 predicts drug-induced phospholipidosis. Journal of lipid research, (2021); 62.‏