The effects of maternal and paternal exposure to tramadol on rat prenatal foetuses

  • Authors

    • El-Balshy R.M Faculty of Science-Benha University
    • Zowail M.E Faculty of Science-Benha University
    • Nafie E. H Faculty of Science-Benha University
    • Abou-Bakr S.H Faculty of Science-Benha University
    2021-06-01
    https://doi.org/10.14419/ijbr.v9i1.31558
  • Tramadol, Endoskeleton System, Histopathology, Teratogenicity, 20-Day-Old Albino Rat Foetus.

  • Abstract

    The presented study was conducted to investigate the effects of different doses of tramadol on the prenatal foetuses of rat at 20th day of gestation. The animals were divided into five groups; Control group (C), received saline orally; G1administered with (1/6 LD50; 50 mg/kg); G2 was given (1/10 of LD50; 30 mg/kg) and G3& G4 were treated with low doses of tramadol (1/50 of LD50; 6 mg/kg) and (1/100 of LD50; 3 mg/kg) respectively. Males and females were administered with tramadol for 7 days before mating, then they mate with each other and pregnant females continued treatment with tramadol to the 20th day of gestation. Tramadol significantly decreased body weight and length of foetuses and increased percentage of dead foetuses. Besides the early death of foetuscs which become resorbed during the gestation period, few foetuses died at the end of gestation period and remain as stillbirth. The percentage of mortality of resorbed foetuses and sillbirth is generally increased in the treated groups. Tramadol treatment caused retarded ossification of some bones and shortness of others. Numerous histopathological changes were detected in liver, kidneys, and lungs of the parentally treated foetuses rat tissues.

     

     

  • References

    1. [1] Abdellatief, R. B.; Elgamal, D. A. and Mohamed, E. E. (2015): Effects of chronic tramadol administration on testicular tissue in rats: an experimental study. Andrologia., 47(6): 674–679. https://doi.org/10.1111/and.12316.

      [2] Abdullah, B. (2018): Evaluation of the Potential Fetotoxic Effects of Tramadol in Female Pregnant Mice. Zagazig Veterinary Journal. 46 (1): 1-7. https://doi.org/10.21608/zvjz.2018.7617.

      [3] Alghobary, M.; El-Bayoumy, Y.; Mostafa, Y.; Mahmoud, el-H. M. and Amr, M. (2010): Evaluation of tramadol on demand vs. daily paroxetine as a long-term treatment of lifelong premature ejaculation. J Sex Med., 7 (8): 2860-2867. https://doi.org/10.1111/j.1743-6109.2010.01789.x.

      [4] Alvarado, C.; Guzman, A.; Diaz, E. and Patino, R. (2005): Synthesis of tramadol and analogous. J Mex Chem Soc., 49(4): 324-327.

      [5] Atallah, M. N.; Badawy, G. M.; El-Garawani, I. M.; Abdallah, F. S. and El-Borm, H. T. (2020): Effect of Selenium against Nalufin Induced Morphological and Endo-Skeletal Abnormalities in Chick Embryos. EJPMR. 7(4): 591-600.

      [6] Atici, S.; Cinel, L.; Cinel, I.; Doruk, N.; Aktekin, M.; Akca, A.; Camdeviren, H. and Oral, U. (2004): Opioid neurotoxicity: comparison of morphine and tramadol in an experimental rat model. Intern J Neuroscience. 114(8): 1001-1011. https://doi.org/10.1080/00207450490461314.

      [7] 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): 245-252. https://doi.org/10.1007/BF02703705.

      [8] Awadalla, E. A. and Salah-Eldin, A. E. (2015): Histopathological and Molecular Studies on Tramadol Mediated Hepato-Renal Toxicity in Rats. IOSR Journal of Pharmacy and Biological Sciences. 10(6): 90-102.

      [9] Awadalla, E. A. and Salah-Eldin, A. E. (2016): Molecular and histological changes in cerebral cortex and lung tissues under the effect of tramadol treatment. Biomed Pharmacother., 82: 269-280. https://doi.org/10.1016/j.biopha.2016.04.024.

      [10] Badawy, G.; Sakr, S. and Atallah, M. (2012): Comparative study of the skeletogenesis of limb autopods in the developing chick Gallus domesticus and Toad Buforegularis. RJPBCS. 3: 966-988.

      [11] Banchroft, J. D.; Stevens, A. And Turner, D. R. (1996): Theory and Practice of Histological Techniques (4th ed.). UK, London: Churchil Livingstone.

      [12] Barbosa, J.; Faria, J.; Garcez, F.; Leal, S.; Afonso, L.P.; Nascimento, A.V.; Moreira, R.; Queirós, O.; Carvalho, F. and Dinis-Oliveira, R. J. (2020): Repeated Administration of Clinical Doses of Tramadol and Tapentadol Causes Hepato- and Nephrotoxic Effects in Wistar Rats. Pharmaceuticals. 13(7): 149. https://doi.org/10.3390/ph13070149.

      [13] Bateman, B. T.; Hernandez-Diaz, S.; Rathmell, J. P.; Seeger, J. D.; Doherty, M.; Fischer, M. A. and Huybrechts, K. F. (2014): Patterns of opioid utilization in pregnancy in a large cohort of commercial insurance beneficiaries in the United States. Anesthesiology. 120(5): 1216–1224. https://doi.org/10.1097/ALN.0000000000000172.

      [14] Beakley, B. D.; Kaye, A. M. and Kaye, A. D. (2015): Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician. 18(4):395-400. https://doi.org/10.36076/ppj.2015/18/395.

      [15] Bidlack, J. M. (2000): Detection and function of opioid receptors on cells from the immune system. Clinical and diagnostic laboratory immunology. 7(5): 719–723. https://doi.org/10.1128/CDLI.7.5.719-723.2000.

      [16] Borna, H. and Borna, S. (2012): Tramadole withdrawal in a neonate: a case report. Tehran Univ Med J., 70(6): 389-392.

      [17] Coluzzi, F.; Valensise, H.; Sacco, M. and Allegri, M. (2014): Chronic pain management in pregnancy and lactation. Minerva Anestesiol., 80(2): 211-224.

      [18] Coluzzi, F.; Scerpa, M. S. and Centanni, M. (2020): The Effect of Opiates on Bone Formation and Bone Healing. Curr Osteoporos Rep., 18(3): 325-335. https://doi.org/10.1007/s11914-020-00585-4.

      [19] Desai, R. J.; Hernandez-Diaz, S.; Bateman, B. T. and Huybrechts, K. F. (2014): Increase in prescription opioid use during pregnancy among Medicaid-enrolled women. Obstet Gynecol., 123(5): 997–1002. https://doi.org/10.1097/AOG.0000000000000208.

      [20] Eassa, B. I. and El-Shazly, M. A. (2013): Safety and efficacy of tramadol hydrochloride on treatment of premature ejaculation. Asian J Androl., 15(1): 138–142. https://doi.org/10.1038/aja.2012.96.

      [21] Eizadi-Mood, N.; Ozcan, D.; Sabzghabaee, A. M.; Mirmoghtadaee, P. and Hedaiaty, M. (2014): Does naloxone prevent seizure in tramadol intoxicated patients?. Int J Prev Med., 5(3): 302–307.

      [22] El-Gaafarawi, I. I. (2006): Biochemical toxicity induced by tramadol administration in male rats. Egypt J Hosp Med., 23(1): 353–362. https://doi.org/10.21608/ejhm.2006.17946.

      [23] El-Hadidy, M. A. and El-Gilany, A. H. (2014): Physical and sexual well-being during and after tramadol dependence. MECPsych., 21: 148-151. https://doi.org/10.1097/01.XME.0000449839.69324.71.

      [24] Elkhateeb, A.; El Khishin, I.; Megahed, O. and Mazen, F. (2015): Effect of Nigella sativa Linn oil on tramadol-induced hepato- and nephrotoxicity in adult male albino rats. Toxicol Rep., 2(1): 512–519. https://doi.org/10.1016/j.toxrep.2015.03.002.

      [25] Elmanama, A. A.; Abu Tayyem, N. E. S.; Essawaf, H. N. and Hmaid, I. M. (2015): Tramadol-Induced Liver and Kidney Toxicity among Abusers in Gaza Strip, Palestine. Jordan Journal of Biological Sci., 8(2): 133-137. https://doi.org/10.12816/0027559.

      [26] Elnazsirous; Vatanpour, H.; Abu Torabi, A. and Asl, B. M. (2020): The Evaluation of Teratogenic Effects of Tramadol on Mouse Fetuses. P J M H S., 14(2): 1155-1161.

      [27] 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.

      [28] Ezzatabadipour, M.; Majidi, M.; Malekpour-afshar, R.; Eftekharvaghefi, S. and Nematollahi-mahani, S. (2011): The effects of morphine on tissue structure of the growth plate in male rats. Iran J Basic Med Sci., 14(6): 514-520.

      [29] Glassroth, J.; Adams, G. D. and Schnoll, S. (1987): The impact of substance abuse on the respiratory system. Chest. 91(4): 596-602. https://doi.org/10.1378/chest.91.4.596.

      [30] Grond, S. and Sablotzki, A. (2004): Clinical pharmacology of tramadol. Clinical Pharmacokinetics. 43(13): 879-923. https://doi.org/10.2165/00003088-200443130-00004.

      [31] Janas, A. and Folwarczna, J. (2017): Opioid receptor agonists may favorably affect bone mechanical properties in rats with estrogen deficiency-induced osteoporosis. Naunyn Schmiedebergs Arch Pharmacol., 390(2): 175–185. https://doi.org/10.1007/s00210-016-1295-6.

      [32] Johnson, J. L. and Leff, M. (1999): Children of substance abusers: overview of research findings. Pediatrics. 103 (5 Pt 2): 1085-1099.

      [33] Karch, S. B. and Stephens, B. G. (2000): Toxicology and pathology of deaths related to methadone: retrospective review. West J Med., 172(1): 11–14. https://doi.org/10.1136/ewjm.172.1.11.

      [34] Karch, S. B. (2002): Opiates. In S. B, Karch (Ed.). Karch's Pathology of Drug Abuse (pp. 313-456). Florida, Boca Raton: CRC Press.

      [35] King, T.; Vardanyan, A.; Majuta, L.; Melemedjian, O.; Nagle, R.; Cress, A. E.; Vanderah, T. W.; Lai, J. and Porreca, F. (2007): Morphine treatment accelerates sarcoma-induced bone pain, bone loss, and spontaneous fracture in a murine model of bone cancer. Pain., 132(1-2):154-168. https://doi.org/10.1016/j.pain.2007.06.026.

      [36] Krajnik, M.; Schäfer, M.; Sobański, P.; Kowalewski, J.; Bloch-Bogusławska, E.; Zylicz, Z. and Mousa, S. A. (2010): Local pulmonary opioid network in patients with lung cancer: a putative modulator of respiratory function. Pharmacol Rep., 62(1): 139-149. https://doi.org/10.1016/S1734-1140(10)70251-6.

      [37] Lalley, P. (2008): Opioidergic and Dopaminergic modulation of respiration. Respir Physiol Neurobiol., 164(1-2): 160–167. https://doi.org/10.1016/j.resp.2008.02.004.

      [38] Lamminpää, A. (1991): Hospitalizations due to poisoning in Finland in 1978–1984. J Toxicol Clin Toxicol., 29(1):111-129. https://doi.org/10.3109/15563659109038602.

      [39] Lee, S. H.; Cho, S. Y.; Lee, H. G.; Choi, J. I.; Yoon, M. H. and Kim, W. M. (2013): Tramadol induced paradoxical hyperalgesia. Pain Phys., 16(1):41–44. https://doi.org/10.36076/ppj.2013/16/41.

      [40] Loughrey, M. B.; Loughrey, C. M.; Johnston, S. and O’Rourke, D. (2003): Fatal hepatic failure following accidental tramadol overdose. Forensic Sci Int., 134(2-3): 232-233. https://doi.org/10.1016/S0379-0738(03)00132-4.

      [41] Matthiesen, T.; Wöhrmann, T.; Coogan, T. P. and Uragg, H. (1998): The experimental toxicology of tramadol: an overview. Toxicol Lett., 95(1): 63-71. https://doi.org/10.1016/S0378-4274(98)00023-X.

      [42] Mercadante, S. and Arcuri, E. (2004): Opioids and renal function. J Pain. 5: 2–19. https://doi.org/10.1016/j.jpain.2003.09.007.

      [43] Mogren, I. M. and Pohjanen, A. I. (2005): Low back pain and pelvic pain during pregnancy: prevalence and risk factors. Spine. 30(8): 983–991. https://doi.org/10.1097/01.brs.0000158957.42198.8e.

      [44] Muslim, Z. Z. (2018): The Biochemical and Histological Effects of Tramadol on Liver and Kidney of Albino Mice. Thi-Qar Medical Journal. 15(1): 43-57.

      [45] Pérez-Castrillón, J. L.; Olmos, J. M.; Gómez, J. J.; Barrallo, A.; Riancho, J. A.; Perera, L.; Valero, C.; Amado, J. A. and González-Macías, J. (2000): Expression of opioid receptors in osteoblast-like MG-63 cells, and effects of different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells. Neuroendocrinology. 72(3):187-194. https://doi.org/10.1159/000054586.

      [46] Pometlová, M.; Hrubá, L.; Šlamberová, R. and Rokyta, R. (2009): Crossfostering effect on postnatal development of rat pups exposed to methamphetamine during gestation and preweaning periods. Int J Dev Neurosci., 27(2):149-155. https://doi.org/10.1016/j.ijdevneu.2008.11.006.

      [47] Raffa, R. B.; Friderichs, E.; Reimann, W.; Shank, R. P.; Codd, E. E.; Vaught, J. L. (1992): Opioid and non-opioid components independently contribute to the mechanism of action of tramadol an ‘‘atypical’’ opioid analgesic. J Pharmacol ExpTher., 260(1): 275-285.

      [48] Ragab, I. K. and Mohamed, H. Z. E. (2017): Histological changes of the adult albino rats entorhinal cortex under the effect of tramadol administration: histological and morphometric study. Alex J Med., 53(2): 123-133. https://doi.org/10.1016/j.ajme.2016.05.001.

      [49] Rozisky, J.; Dantas, G.; Adachi, L.; Alves, V.; Ferreira, M.; Sarkis, J. and Torres, I. (2008): Long-term effect of morphine administration in young rats on the analgesic opioid response in adult life. Int J Devl Neur., 26(6): 561-565. https://doi.org/10.1016/j.ijdevneu.2008.05.005.

      [50] Saleem, R.; Iqbal, R.; Abbas, M. N.; Zahra, A.; Iqbal, J. and Ansari, M. S. (2014): Effects of tramadol on histopathological and biochemical parameters in mice (Mus musculus) model. Glob J Pharm., 8(1):14–19.

      [51] Samaka, R.M.; Girgis, N. F. and Shams, T. M. (2012): Acute toxicity and dependence of tramadol in albino rats: Relationship of Nestin and Notch 1 as stem cell markers. J of American Science. 8(6): 313-327.

      [52] Santos, A. S.; Azevedo, E. N.; Oliveira-Filho, R. M.; Simões, M. and Kulay, J. L. (2001): Effects of chronic use of Tramadol on Pregnant Albino Rats. Rev Bras Ginecol Obstet., 23(2):113-117. https://doi.org/10.1590/S0100-72032001000200009.

      [53] Shadid, S. and Barrett, J. (2013): Opioid-induced osteoporosis: assessing causes and treatments. PPM. 13(10): 870-878.

      [54] Sheweita, S. A.; Almasmari, A. A. and El-Banna, S. G. (2018): Tramadol-induced hepato- and nephrotoxicity in rats: Role of Curcumin and Gallic acid as antioxidants. PLoS One., 13(8): e0202110. https://doi.org/10.1371/journal.pone.0202110.

      [55] Singh, V. P.; Singh, N. and Jaggi, A. S. (2013): A Review on Renal Toxicity Profile of Common Abusive Drugs. Korean J Physiol Pharmacol., 17(4): 347–357. https://doi.org/10.4196/kjpp.2013.17.4.347.

      [56] Simeon, G. and Abbey, S. (2018): Some Marker Enzymes and Histological Alteration on the Administration of Tramadol Hydrochloride on Rat Liver. Modern Research in Inflammation. 7(1): 9-20. https://doi.org/10.4236/mri.2018.71002.

      [57] Šlamberová, R. (2012): Drugs in pregnancy: the effects on mother and her progeny. Physiol Res., 61(Suppl 1): S123-135. https://doi.org/10.33549/physiolres.932357.

      [58] Tao, Q.; Stone, D. J.; Borenstein, M. R.; Codd, E. E. and Coogan, T. P. (2002): Differential tramadol and O-desmethyl metabolite levels in brain vs plasma of mice and rats administered tramadol hydrochloride orally. J Clin Pharm Therap., 27(2): 99-106. https://doi.org/10.1046/j.1365-2710.2002.00384.x.

      [59] Thaete, L. G.; Levin, S. I. and Dudley, A. T. (2013): Impact of anaesthetics and analgesics on fetal growth in the mouse. Lab Anim., 47(3): 175-183. https://doi.org/10.1177/0023677213480769.

      [60] Todorović, M. S.; Mitrović, S.; Aleksandrić, B.; Mladjenović, N. and Matejić, S. (2011): Association of pulmonary histopathological findings with toxicological findings in forensic autopsies of illicit drug users. Vojnosanit Pregl., 68(8):639-642. https://doi.org/10.2298/VSP1108639T.

      [61] Tolman, K. G. (1998): Hepatotoxicity of non-narcotic analgesics. Am J Med., 105(1B): 13S-19S. https://doi.org/10.1016/S0002-9343(98)00070-9.

      [62] Warner, E. A. (2012): Opioids for the treatment of chronic noncancer pain. Am J Med., 125(12):1155–1161. https://doi.org/10.1016/j.amjmed.2012.04.032.

      [63] Wendell, A. D. (2013): Overview and epidemiology of substance abuse in pregnancy. Clin Obstet Gynecol., 56(1): 91-96. https://doi.org/10.1097/GRF.0b013e31827feeb9.

      Yamanaka, T. and Sadikot, R. T. (2013): Opioid effect on lungs. Respirology., 18(2): 255-262. https://doi.org/10.1111/j.1440-1843.2012.02307.x

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    R.M, E.-B., M.E, Z., E. H, N., & S.H, A.-B. (2021). The effects of maternal and paternal exposure to tramadol on rat prenatal foetuses. International Journal of Biological Research, 9(1), 6-16. https://doi.org/10.14419/ijbr.v9i1.31558

    Received date: 2021-04-28

    Accepted date: 2021-05-19

    Published date: 2021-06-01