Al-Qadisiyah Journal of Veterinary Medicine Sciences

Role of Amlodipine Besylate in Prevention or Attenuation of Hepatic Centrilobular Necrosis Induced by CCl4 in Rabbit Models

Document Type : Research Paper

Author

Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of AL-Qadisiyah, Iraq

Abstract

Centrilobular necrosis of hepatic tissue is a major cause of acute liver injury associated with cellular death and impairment of liver functions. It was experimentally induced by hepatotoxic  substances called carbon tetrachloride. Eighteen healthy domestic rabbits were used to evaluate the hepatoprotective activity of amlodipine besylate, they were allocated to three groups; G1 (negative control), GII (positive control) and GIII (treatment group). G1 received only distilled water 3 ml orally, GII was given single dose of carbon tetrachloride ( 1.5 ml/kg body weight) orally as a mixture with olive oil to induce liver damage. Whereas GIII was given amlodipine besylate (1.25 mg/body weight) orally one hour before induction of hepatic centrilobular necrosis by carbon tetrachloride, then the same dose of tested agent continued daily for two successive days after the administration of carbon tetrachloride. The duration of experiment was 3 days i.e. 72 hours.Blood samples were taken for biochemical analysis of liver functions at 2 occasions, 24 and 72 hour after induction of hepatic centrilobular necrosis to determine the values of serum  alanine aminotansferase (SALT), serum aspartate aminotansferase (SAST), serum alkaline phosphatase (SALP), total serm bilirubin (TSB) and total serum protein (TSP) of the tested animals. The histopathological examination of liver samples was then done after 72 hours to check the microscopic changes of the liver tissue. Amlodipine besylate with this daily dose showed a significant reduction (p<0.05) in the levels of serum ALT, AST , ALP, total bilirubin and significant elevation (p<0.05) in the level of total serum protein in comparison to GII, both after 24 hour and 72 hour of carbon tetrachloride administration. Histologically, liver sections showed that amlodipine produced no necrosis, mild fatty change, mild inflammatory infiltration and mild congestion when compared with that of GII. As conclusion, Amlodipine besylate was proved to have a significant hepatoprotective activity on hepatic centrilobular necrosis model .

Keywords

References
1. Kumar V, Cotran RS, Robbins SL. ROBBINS Basic Pathology. 7th ed. Philadelphia: Saunders; 2003. p. 591-598.
2. Henry JB. Clinical Diagnosis and Management by Laboratory Methods. 20th ed. Vol. 1. Philadelphia: W.B. Saunders Company; 2001. p. 272-274.
3. Christopher H, Edwin R, Nichoas AB, Nichi R. DAVIDSON'S: Principles and Practice of Medicine. 19th ed. India: Churchill Livingstone; 2002. p. 834-848.
4. Klaassen CD. Casarett and Doull's Toxicology: The Basic Science of Poisons. 6th ed. Vols. 1, 2. USA: McGraw-Hill; 2001. p. 472-487, 876-887.
5. Ohta Y, Kongo-Nishimura M, Matsura T, Yamada K, Kitagawa A, Kishikawa T. Melatonin Prevents Disruption of Hepatic Reactive Oxygen Species Metabolism in Rats Treated with CCl4. Dept. of Chemistry. Japan. 2004;36(1):7-10. https://doi.org/10.1046/j.1600-079X.2003.00091.x
6. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive Oxygen Species in Inflammation and Tissue Injury. Antioxid Redox Signal. 2014;20(7):1126-1167. https://doi.org/10.1089/ars.2012.5149
7. Macfarlane PS, Reid R, Callander R. Pathology Illustrated. 5th ed. China: Churchill Livingstone; 2000. p. 342-362.
8. Fares H, DiNicolantonio JJ, O'Keefe JH, Lavie CJ. Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes. Open Heart. 2016;3(2). https://doi.org/10.1136/openhrt-2016-000473
9. Amlodipine. Available from: https://livertox.nih.gov/Amlodipine.htm. Accessed 9 December 2018.
10. Dashti H. Liver Injury and Liver Cirrhosis: An Experimental and Clinical Study. Dept. of Surgery. London. 1986. p. 32-34, 79-81.
11. Ritter C, Reinke A, Andrades M, Martins MR, Rocha J, Menna-Barreto S, et al. Protective Effect of N-acetylcysteine and Deferoxamine on CCl4-Induced Acute Hepatic Failure in Rats. Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, SC, Brazil. 2004;32(10):2079-83. https://doi.org/10.1097/01.CCM.0000142699.54266.D9
12. Sherlock S, Dooley J. Disease of the liver and Biliary System. 11th ed. Italy: Blackwell Science; 2002. p. 111-123, 341-342.
13. Taira Z, Yabe K, Hamaguchi Y, Hirayama K, Kishimoto M, Ishida S, et al. Effect of Sho-saiko-to Extract and Its component, Basicalin, Basicline, Glycyrrhizin and Glycyrrhetic Acid on Pharmacokinetic Behavior of Salicylamide in CCl4 Intoxicated Rats. Food Chem Toxicol. Japan. 2004;42(5):803-7. https://doi.org/10.1016/j.fct.2003.12.017
14. Javl'e P, Yates J, Kynaston HG, Parsons KF, Jenkins SA. Hepatosplanchnic Haemodynamics and Renal Blood Flow and Function in Rats with Liver Failure. Dept. of Urology. Liverpool. UK. 1998;43:272-279. https://doi.org/10.1136/gut.43.2.272
15. Hung DY, Chang P, Cheung K, McWhinney B, Masci PP, Weiss M, Roberts MS. Cationic Drug Pharmacokinetics in Diseased Livers Determined by Fibrosis Index, Hepatic Protein Content, Microsomal Activity, and Nature of Drug. Dept. of Medicine. Australia. 2002;301(3):1079-1087. https://doi.org/10.1124/jpet.301.3.1079
16. Varghese G, Madi L, Ghannam M, Saad R. A possible increase in liver enzymes due to amlodipine: a case report. SAGE Open Med Case Rep. 2020. https://doi.org/10.1177/2050313X20917822
17. Horman JYK, Patel P, Schultz M, Kraschnewski J. Amlodipine-Induced Liver Injury. Cureus. 2022 Mar;14(3).
Al-Qadisiyah Journal of Veterinary Medicine Sciences
Volume 22, Issue 1
May 2023
Pages 11-16
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