Effects of Tramadol on Histopathological and Biochemical Parameters in Male Rabbits
The present study was designed to investigate the effects of different doses of tramadol hydrochloride (TH) on histopathological and biochemical changes in male rabbits. Fifteen healthy males local breed rabbits weighting 1.6 - 1.8 kg were distributed randomly and equally into three groups, housed under laboratory condition at the same room with natural light 1 dark cycle at 23 +3 ºC temperature, and given free access to commercial balanced diet and water ad libitum all over the experimental period. Group T1injected intramuscularly(i.m) with tramadol 10 mg/kg b.w for 15 days, while the T2 group injected i.m with tramadol 15mg/kg b.w for 15 days and the 3rd groups T3 is control inoculated with distilled water 1/M at the same period. Blood samples were collected for biochemical analysis of creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). After sacrificed the animals, liver and kidney samples were obtained and fixed in 10% buffered formalin, processed, embedded in paraffin, sectioned, and stained with haematoxylin and eosin (H&E) for histopathological changes. The histopathological examination showed cellular degeneration characterized by vacuolization in the endothelium cells of renal tubules of the kidney and degeneration and pyknotic of the hepatocyte nuclei in the liver of the tramadole administrated rabbits only. The biochemical assay revealed that administration of tramadol for 15 days increased serum creatinine, ALT, AST, and ALP in treated rabbits compared to the control. The maximum increases was recorded in group T2, administrated i.m with 15mg/kg tramadol. In conclusion the tramadol side effects should be avoided during long term therapy especially in large doses.
Tramadol Hydrochloride, Rabbits, Creatinine, ALT, AST, ALP
ADRAC. (2003). Tramadol - four years' experience. Aust. Adv. Drug. React. Bull. 22:2-3.
Aldalou AR, Abdel-Aziz I and Shahwan O 2014: Impact of giving sildenafil (Viagra) / Tramadol (Tramal) combination on the blood of domestic rabbits. Journal of Science. Vol 4 Issue 3: 162-169.
Atici S, Cinel I, Cinel L, Doruk N, Eskandari G and Oral U (2005). Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model. J. Biosci. 30(2):245-52.
Babul N, Noveck R, Chipman H, Roth S H, Gana T and Albert K (2004). Efficacy and safety of extended-release, once-daily tramadol in chronic pain: a randomized 12-week clinical trial in osteoarthritis of the knee. Journal of Pain and Symptom Management. 28(1): 59–71.
Bartels H, Bohmer M and Heierli C (1972). Serum creatinine determination without protein precipitation. Clinica.Chemica.Acta.37: 193-197.
Bessey O A, Lowry O H and Brock M J (1946). Method for rapid determination of alkaline phosphates with 5 cubic millimeters of serum. Journal of Biological Chemistry. 164:321-329.
Dayer P, Desmeules J and Collart L (1997). Pharmacology of tramadol. Drugs. 2:18-24.
Elkhateeb E, El Khishin I, Megahed O and Mazen F (2015). Effect of Nigella sativa Linn oil on tramadol-induced hepatoand nephrotoxicity in adult male albino rats.Toxicology Reports. 2 : 512–519
El-Wessemy A M (2008).Histopathological and ultra-structural studies on the side effects of the analgesic drug tramadol on the liver of albino mice, Egypt. J. Zool. 50 423–442.
Feldmann G (2006). Liver apoptosis. Gastroenterol. Clin. Biol. 30(4):533-45.
Gaafarawi I I (2006). Biochemical Toxicity Induced By Tramadol Administration in Male Rats. The Egyptian Journal of Hospital Medicine, 23: 353-362.
Lee R C, Tavish M C and Sorkin E M (1993). Tramadol: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states; Drugs 46 313–340
Lehmann K A (1997). Tramadol in acute pain. Drugs. 2:25-33.
Luna L G (1968). Manual of histological staining methods of the armed forces institute of pathology. 3rd edition. New York, Mcgraw-Hill.
Loughrey M B, Loughrey CM, Johnston S and Rourke D O (2003). Fatal hepatic failure following accidental tramadol overdose, Forensic Sci. Int. 134 (2–3) 232–235.
Lyman JL ( 1986). Blood urea nitrogen and creatinine. Emergency Medicine Clinics of North America, 4(2): 223-33.
Nehru B and Anand P (2005). Oxidative damage following chronic aluminum exposure in adult and pup rat brains, J. Trace Elem. Med. Biol. 19: 203–208.
Perry PW, Doumas BT, Bayse D D, Butler T, Cohen A, Fellows W, Garber C C, Howell B, Koch T, Krishnamurthy S, Louderback A, McComb R B, Miller D, Miller RR., Rand RN and Schaffer R (1983). A candidate reference method for determination of bilirubin in serum. Test for transferability. Clin Chem. 29 (2):297-301.
Raffa RB (2008). Basic pharmacology relevant to drug abuse assessment: tramadol as example. J. Clin. Pharm. Ther. 33(2):101-8.
Reitman S and Frankel S (1957). A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am.J.Clin.Pathol. 28(1):56-63.
Salem EA, Wilson SK, Bissada NK, Delk JR, Hellstrom WJ and Cleves MA (2008). Tramadol HCL has Promise in On-Demand Use to Treat Premature Ejaculation. J. Sex. Med. 5:188–193.
Senay E C, Adams E H, Geller A, Jnciardi J A, Munoz A, Schnoll SH, Woody GE and Cicero TJ (2003). Physical dependence on Ultram (tramadol hydrochloride)/: both opioid like and a typical withdrawal symptom occur. Drug Alcohol. Depend. 69(3):233- 241.
Singhal PC, Sharma P, Sanwal V, Prasad A, Kapasi A, Ranjan R, Franki N, Reddy K and Gibbons N (1998). Morphine modulates proliferation of kidney fibroblasts. Kidney International. 53:350-357.
Stitik TP, Altschuler E and Foye PM (2006). Pharmacotherapy of osteoarthritis. Am. J. Phys. Med. Rehabil. 85(11 Suppl):S15-28.
Threlkeld M, Parran TV, Adelman CA, Grey SF and Yu J (2006). Tramadol versus buprenorphine for the management of acute heroin withdrawal: a retrospective matched cohort controlled study. Am J Addict. 15(2):186-91.
Yang RZ, Park S, Reagan WJ, Goldstein R, Zhong S, Lawton M, Rajamohan F, Qian K, Liu L and Gong DW (2009). Alanine aminotransferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity. Hepatology. 49(2):598-607.
Wu WN, Mcknown LA, Gauthier AD, Jones WJ and Raffa RB (2001). Metabolism of analgesic, tramadol hydrochloride, in ratand dog. Xenobiotica, 31: 423-441.