The Biochemical and Histological Effects of Tramadol on Liver and Kidney of Albino Mice


  • Zahraa Zuhair Muslim Assistant Lecturer / Kut Technical Institute


           The aim of this study is to assess the effect of usage of tramadol in liver and kidney in albino mice. Twenty albino mice were taken (25-30) gm and divided in to two groups, group I (10 mice) which received normal saline intramuscularly and group II (10 mice) which received) 25 mg /kg body weight (daily of tramadol intramuscularly for 40 days, the biochemical assay showed significant increase (p value < 0.05) in the Aspartate aminotransferase (AST), alanine aminotransferase (ALT), Urea and Creatinine in experimental group compared to the control group. The histological examination regarded for liver tissues degenerative changes in the hepatocytes, dilated central vein, focal necrotic area, congested vessel, congested hepatic vein and cytolysis while kidney tissues show widening bowman capsule, interstitial nephritis, necrosis, degenerative change, lymphocyte infiltration in renal interstitial nephritis and degenerative changes in renal proximal tubules.


Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879–923.

Trescot A.M., Datta S., Lee M., Hansen H. Opioid pharmacology. Pain Physician. 2008;11:S133–S153.

Afshari R, Afshar R, Mégarbane B 2011. Tramadol overdose: review of the literature. Ré‐ animation.;20(5):436-41.

Dickman A. Tramadol: a review of this atypical opioid. European Journal of Palliative Care. 2007;14(5):181–185.

Stoops WW, Lofwall MR, Nuzzo PA, Craig LB, Siegel AJ, Walsh SL2012. Pharmacody‐ namic profile of tramadol in humans: influence of naltrexone pretreatment. Psycho‐pharmacology (Berl).;223(4):427-38.

Schnitzer TJ. Update of ACR guidelines for osteoarthritis: role of the coxibs. Journal of pain and symptom management. 2002;23(4):S24-S30.

Agrawal A, Diwan S, Mahajan R. Severe delirium following single dose of tramadol. Indian journal of medical sciences. 2009;63(2):80-1.

Goldfrank LR, Flomenbaum N, Lewis NA, Howland MA, Hoffman RS, Nelson LS, editors. Goldfrank's 2000Toxicologic Emergencies. 7 ed. New York: McGraw-Hill Medical;916.

Shi Q, Hong H, Senior J, Tong W. Biomarkers for drug-induced liver injury, Expert Rev. Gastroenterol. Hepatol., 2010, vol. 4 (pg. 225-234)

Assis DN, Navarro VJ. Human drug hepatotoxicity: a contemporary clinical perspective. Expert Opin Drug Metab Toxicol 2009; 5: 463-473.

Marquardt KA Alsop JA Albertson TE. Tramadol exposures reported to statewide poison control system. Ann Pharmacother 2005; 39: 1039–1044

Sanaei-Zadeh H. Tramadol intoxication and shoulder pain. European review for medical and pharmacological sciences. 2014;18(2):285.

Lofwall MR, Babalonis S, Nuzzo PA, Siegel A, Campbell C, Walsh SL. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial. Drug and alcohol dependence. 2013;133(1):188-197.

El-Naggar M, El-Sehly WM, Morad GM, Eeed M, Hassan M. P19: The toxic effect of prolonged Ultram administration on cerebral cortex of albino rats: Toxicological and histological study. Experimental and Toxicologic Pathology. 2009;61(3):290.

Kaplowitz N. Drug-induced liver injury. Clin Infect Dis 2004;38: Suppl 2: S44-S48

Eizadi-Mood N, Ozcan D, Sabzghabaee AM, Mirmoghtadaee P, Hedaiaty M. Does naloxone prevent seizure in tramadol intoxicated patients? Int J Prev Med. 2014; 5:302–7.

Lee CR, McTavish D, Sorkin EM. Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs 1993; 46: 313–40

Wu WN, Mcknown LA, Gauthier AD, Jones WJ and Raffa RB. Metabolism of analgesic, tramadol hydrochloride, in ratand dog. Xenobiotica. 2001; 31: 423-441.

Yang RZ, Park S, Reagan WJ. Alanine amino transferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity. Hepatology. 2009; 49: 598-607.

Atici S, Cinel I, Cinel L, Doruk N, Eskandari G, Oral U. Liver and kidney toxicity in chronic use of opioids: An experimental long term treatment model. J Biosci. 2005; 30:245–52.

Borzelleca, J.F., J.L. Egle, L.S. Harries, D.N. Johnson, J.B. Terrill and J.A. Belleville. Toxicological evaluation of mμ-agonists. Part 1: Assessment of toxicity following 30 days of repeated oral dosing of male and female rats with levo-alphaacetylmethadol HCL (LAAM). Journal of Applied Toxicology. 1994; 14: 435-446.

Panchenko L. F., S.V. Pirozhkov, A.V. Nadezhdin, V.I. Baronets and N.N. Usamanova. Lipid peroxidation, peroxyl radical-scavenging system of plasma and liver and heart pathology in adolescence heroin users. Vopr.Med. Khim. 1999; 45:501-506.

Obed Khalid Ali, AL- Jmor Sara Ahmed, Al-Graibawi Mawlood. A. A. Effects of Tramadol on Histopathological and Biochemical Parameters in Male Rabbits. American Journal of Biology and Life Sciences. Vol. 3, No. 3, 2015, pp. 85-90. [24] Habibian- Dehkordi S, Bigham-Sadegh A, Abaspour A, Beigi Brojeni N. Intravenous administration of tramadol hydrochloride in sheep. J Comp Clin Pathol. 2010; 21: 289- 293

Giannini, E.G., R. Testa and V. Savarino. Liver enzyme alteration: a guide for clinicians Canadian Medical Association Journal. 2005; 172(3): 367-379.

Shadnia S, Soltaninejad K, Heydari K, Sasanian G, Abdollahi M. Tramadol intoxication: a review of 114 cases. Hum Exp Toxicol. 2008; 27: 201-205.

Lyman, J.L. Blood urea nitrogen and creatinine. Emergency Medicine Clinics of North America. 1986; 4(2): 223-33.

El-Gaafarawi I.I. Biochemical effects of some analgesics. Egypt. J. Hosp. Med. 2006; 21:16–32.

Shah NH, Thomas E, Jose R, Peedicayil J. Tramadol inhibits the contractility of isolated human myometrium. Auton Autacoid Pharmacol. 2013; 33:1–5.

Albarakai, A.Y. & Abd Elrhman Alsbery, H.M. Evaluation of the hepatoprotective efficacy of Moringa oleifera on tramal-induced liver toxicity in animal modules. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2016; 7. 1494-1501.

Youssef SH, Zidan AHM. Histopathological and Biochemical Effects of Acute and Chronic Tramadol Drug Toxicity on Liver, Kidney and Testicular Function in Adult Male Albino Rats. J Med Toxicol Clin Forensic Med. 2016;1:2