Amitriptyline Induced Alterations in Liver and Kidney Functions and Structures in Male Rats

Main Article Content

Fathy A. M. Atta
Ehab Tousson
Noha A. Dabour
Ahmed A. Massoud
Ahmed F. Hasan


Aims: Depression is a mental health issue that starts most often in early adulthood and it is a common and recurrent disorder causing significant morbidity and mortality worldwide. Amitriptyline is a tricyclic antidepressant that is known to inhibit the presynaptic reuptake of serotonin, norepinephrine, and inhibitor of mitochondrial functions and induces apoptosis in several tissues. This study aims to identify the changes in liver and kidney structure and functions after treatment of male rats with Amitriptyline drugs.

Materials and Methods: A total of 20 male albino rats were randomly and equally divided into 2 groups (G1, control group that included animals that did not receive any treatment during the experimental period. G2, Amitriptyline (Tryptizol; El Kahira Pharm And Chem Ind Co) group in which rats were injected intraperitoneally with Amitriptyline (100 mg/kg body weight/daily) for four weeks).

Results: The current results revealed that; Amitriptyline treatments significantly (P <0.05) increased the levels of serum ALT, AST, ALP, urea, creatinine, sodium ions, chloride ions and liver  and kidney damages as compared to control. In contrast; a significant (P <0.05) decrease in albumin, and total protein, potassium ions and calcium ions in Amitriptyline group was reported when compared with control group.

Conclusion: Amitriptyline has many side effects on rat liver and kidney, it induced liver and kidney toxicity and tissue injury were it metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons.

Amitriptyline, antidepression, liver and kidney, rats

Article Details

How to Cite
Atta, F. A. M., Tousson, E., A. Dabour, N., A. Massoud, A., & F. Hasan, A. (2019). Amitriptyline Induced Alterations in Liver and Kidney Functions and Structures in Male Rats. Asian Journal of Research in Medical and Pharmaceutical Sciences, 7(4), 1-10.
Original Research Article


Rashid T, Heider I. Life Events and Depression. Annals of Punjab Medical College. 2008;2(1).

Fonseca AP, Leala V. Use of Antidepressants to Treat Postpartum Depression, During Breast Feeding. J Depress Anxiety. 2014;3:148.

Ghoneim M, Saber AL, El-Desoky H. Utility Spectrophotometric and Chromatographic Methods for Determination of Antidepressant Drug Sulpiride in Pharmaceutical Formulations and Plasma. J Anal Bioanal Tech. 2014;5:183.

El Atrash A, Tousson E, Gad A, Allam S. Hematological and Biochemical Changes Caused by Antidepressants Amitriptyline Induced Cardiac Toxicity in Male Rats. Asian Journal of Cardiology Research. 2019;23:1-6.

Jespersen S. Antidepressant induced sexual dysfunction Part 2: assessment and management. S Afr Psychiatry Rev. 2006; 9:79-83.

Nazari M. Effect of Fluoxetine on the sexual behavior of Drosophila melanogaster, J. Postgr. Medi. Insti. (Peshawar Pakistan). 2011;25(4).

Kavitha BB, Nischal R, Shashank B. Dose Dependent Amitriptyline Induced Sexual Dysfunction in a Migraine Patient. International Journal of Pharmacology and Clinical Sciences. 2016;5(2):62-64.

George S, Acharya LD, Prabhu, AR, Mallayasamy S. Management and treatment outcome of complications of chronic kidney disease patients in a South Indian tertiary care hospital. Int. J. Pharmacol. and Clin Sci. 2013;2:113-120.

Tousson E, Zaki S, Hafez, E Gad A. Biochemical and immunocytochemical studies of the testicular alteration caused by Amitriptyline in adult male rat. Journal of Bioscience and Applied Research. 2018;4(4):418-424.

Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003; 552(2):335-344.

Saggu S, Sakeran M, Zidan N, Tousson E, Mohan A. Rehman H. Ameliorating effect of chicory (Chichorium intybus L.) fruit extract against 4-tert-octylphenol induced liver injury and oxidative stress in male rats. Food and Chemical Toxicology. 2014; 72:138–146.

Moustafa AH, Ali EM, Moselhey SS, Tousson E, El-Said KS. Effect of coriander on thioacetamide-induced hepatotoxicity in rats. Toxicology and Industrial Health. 2014;30(7):621-629.

Al-Rasheed NM, El-Masry TA, Tousson E, Hassan HM, Al-Ghadeer A. Protective potential of grape seed proanthocyandins extract against glivec (Imatinib Mesylate) induced liver toxicity and oxidative stress in male rats. Annual Research & Review in Biology. 2017;20(6):1-9.

El-Moghazy M, Zedan NS, El-Atrsh AM, El-Gogary M, Tousson E. The possible effect of diets containing fish oil (Omega-3) on hematological, biochemical and histopathogical alterations of rabbit liver and kidney. Biomedicine & Preventive Nutrition. 2014;4:371–377.

Basuony M, Hafez E, Tousson E, Massoud A, Elsomkhraty S, Eldakamawy S. Beneficial role of Panax ginseng root aqueous extract against Cisplatin induced blood toxicity in rats. American Journal of Biological Chemistry. 2015;3:1-7.

Tousson E, Tawfeek Z, Abu-Shaeir WA, Hassan H. Methotrexate-induced Hepatic and Renal Toxicity: Role of L-carnitine in Treatment. Biomedicine and Biotechnology. 2014;2(4):85-92.

Eldaim MA, Tousson E, El Sayed IE, El AE, Elsharkawy HN. Grape seeds proanthocyanidin extract ameliorates Ehrlich solid tumor induced renal tissue and DNA damage in mice. Biomedicine & Pharmacotherapy. 2019;115:108908.

Oyouni AA, Saggu S, Ehab Toussonb, Rehman H. Immunosuppressant drug tacrolimus induced mitochondrial nephrotoxicity, modified PCNA and Bcl-2 expression attenuated by Ocimum basilicum L. in CD1 mice. Toxicology Reports. 2018;5:687–694.

El-Masry TA, Al-Shaalan NH, Tousson E, El-Morshedy K, Al-Ghadeer A. P53 expression in response to equigan induced testicular injury and oxidative stress in male rat and the possible prophylactic effect of star anise extracts. Annual Research & Review in Biology. 2017; 14(1):1-8.

Tousson E, Bayomy MF, Ahmed AA. Rosemary extract modulates fertility potential, DNA fragmentation, injury, KI67 and P53 alterations induced by etoposide in rat testes. Biomedicine & Pharmacotherapy. 2018;98:769–774.

Tousson E. Histopathological alterations after a growth promoter boldenone injection in rabbits. Toxicology and Industrial Health. 2016;32(2):299–305.

Tousson E, El-Moghazy M, Massoud A, El-Atrash A, Sweef O, Akel A. Physiological and biochemical changes after boldenone injection in adult rabbits. Toxicology and Industrial Health. 2016;32(1):177–182.

Tousson E, Ibrahim W, Barakat L, Abd El-Hakeem A. Role of proplis administration in boldenone-induced oxidative stress, Ki-67 protein alterations and toxicity in rat liver and kidney. International Journal of Scientific & Engineering Research 2015; 6(8):660-664.

Tortora GJ, Grabowski SR. The digestive system (liver and gallbladder) In: Principles of Anatomy and Physiology, seventh edition, Harper Collins college publishers. New York. 2002;24:792-795.

Shanmugasundaram P, Venkataraman S. Hepatoprotective and antioxidant effects of Hygrophila auriculata (K. Schum) Heine Acanthaceae root extract. Journal of Ethnopharmacology. 2006;104: 124-128.

Salama A, Kasem S, Tousson E, Elsisy MK. Protective role of L-carnitine and vitamin E on the testis of atherosclerotic rats. Toxicology and Industrial Health 2015;31(5):467–474.

Bolkiny Y, Tousson E, El-Atrsh A, Akela M, Farg E. Costus root extract alleviates blood biochemical derangements of experimentally-induced hypo-and hyperthyroidism in mice. Annual Research & Review in Biology. 2019;31(5):1-0.

DeSanty KP, Amabile CM: Antidepressant-induced liver injury. Ann Pharmacother. 2007;41:1201–1211.

Cunningham ML: Acute hepatic necrosis following treatment with amitriptyline and diazepam. Br J Psychiatry. 1965;111: 1107–1109.

Ebuehi OA, Asonye CL. Gender and alcohol consumption affect human serum enzymes, protein and bilirubin. Asian J Biochem. 2007;2:330-6.

Anttila M, Sotaniemi EA, Pelkonen O et al. Marked effect of liver and kidney function on the pharmacokinetics of selegiline. Clin Pharmacol Ther. 2005;77:54–62.

Alm-Eldeen A, Tousson E. Deterioration of glomerular endothelial surface layer and the alteration in the renal function in Rabbits after treatment with a growth promoter Boldenone. Human & Experimental Toxicology. 2012;31(5):465-472.

El-Moghazy M, Tousson E, Sakeran M. Changes in the hepatic and renal structure and function after a growth promoter Boldenone injection in Rabbits. Animal Biology. 2012;62(2):171-180.

Tousson E, Keshta AT, Hussein Y, Fekry RM, Abo-Ghaneima WK. Renal protective effect of Ginkgo biloba and L-carnitine extracts against pentylenetetrazol induced toxicity, oxidative stress, injury and proliferation alternation in epileptic rats. Annual Research & Review in Biology. 2019;28:1-3.

Salama AF, Tousson E, Ibrahim W, Hussein MW. Biochemical and histopathological studies in the PTU-induced hypothyroid rat kidney with reference to the ameliorating role of folic acid. Toxicology and Industrial Health 2013; 29(7):600-608.

Salama AF, Kasem SM, Tousson E, Elsisy MK. Protective role of L-carnitine and vitamin E on the kidney of atherosclerotic rats. Biomedicine & Aging Pathology. 2012;2:212–215.

Łąkowska H, Maciejewski R, Szkodziak P, Staśkiewicz G. Changes in the activity of lysosomal enzymes in rat kidneys in the course of acute pancreatitis. Medical Science Monitor. 2001;7(6):BR1193-7.