Maternotoxicity and fetotoxicity in Rattus norvegicus albinus exposed to tramadol during the late phase of pregnancy.
fetotoxicity
maternotoxicity
opioids
oxidative stress
pregnant
tramadol
Journal
Birth defects research
ISSN: 2472-1727
Titre abrégé: Birth Defects Res
Pays: United States
ID NLM: 101701004
Informations de publication
Date de publication:
15 11 2021
15 11 2021
Historique:
revised:
08
07
2021
received:
03
02
2021
accepted:
04
09
2021
pubmed:
24
9
2021
medline:
25
12
2021
entrez:
23
9
2021
Statut:
ppublish
Résumé
Tramadol, an atypical opioid, is clinically efficacious in treating moderate to severe pain. The aim of current study was to find out the toxicological effects of tramadol exposure to pregnant rats and fetuses during the late phase of pregnancy. Wistar pregnant rats were exposed to 1.25, 2.5, or 5 mg/kg/day tramadol from 14th to 20th day of pregnancy. The same therapy was given to nonpregnant rats for 7 days. The body weight, oral glucose and lipid tolerance tests, and effect on complete blood parameters in both pregnant and nonpregnant rats were determined. On 20th day, maternal placentas were excised and weighed while fetuses were observed for any deformity and growth retardation. Oxidative stress biomarkers were estimated in the liver and kidney tissue homogenates of the pregnant and nonpregnant rats while the whole fetus homogenate was processed for the same. Moreover, histopathology of the liver and kidney of pregnant and nonpregnant rats were carried out. Tramadol administration did not significantly alter the area under curve of the blood glucose and triglyceride levels in both the pregnant and nonpregnant rats. It reduced the live fetuses, placental weights, fetal length, and fetal weights. Tramadol treated pregnant rats showed significantly (p < .05) reduced red blood cells, hematocrit, hemoglobin, and platelets with reference to control group. Similarly, structural abnormalities and malfunctioning of the liver and kidney of pregnant rats were instituted; however, it did not affect the structural integrity of nonpregnant rats. A substantial (p < .001-.0001) altered glutathione and malondialdehyde levels in the fetuses, pregnant, and nonpregnant animals (tissue homogenates) at all dosage levels were indicative of tramadol induced oxidative stress. Furthermore, tramadol exposure resulted in more significant (p < .01-.001) alteration of lipid profile in the pregnant than the nonpregnant animals. Acquired results suggested the maternotoxic and fetotoxic effects of tramadol exposure during the late gestation period.
Substances chimiques
Tramadol
39J1LGJ30J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1407-1421Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Abdullah, B. A. (2018). Evaluation of the potential fetotoxic effects of tramadol in female pregnant mice. Zagazig Veterinary Journal, 46(1), 1-7.
Aboubakr, M., Elbadawy, M., Soliman, A., & El-Hewaity, M. (2014). Embryotoxic and teratogenic effects of norfloxacin in pregnant female albino rats. Advances in Pharmacological Sciences, 2014, 1-6.
Akhtar, M., Rabbani, M., Sharif, A., Akhtar, B., Saleem, A., & Murtaza, G. (2011). Formulation and characterization of modified release tablets containing ionizid using swellable polymers. African Journal of Traditional, Complementary and Alternative Medicines, 8(3), 250-259.
Akhtar, M. F., Ashraf, M., Anjum, A. A., Javeed, A., Sharif, A., Saleem, A., & Akhtar, B. (2016). Textile industrial effluent induces mutagenicity and oxidative DNA damage and exploits oxidative stress biomarkers in rats. Environmental Toxicology and Pharmacology, 41, 180-186.
Atici, S., Cinel, I., Cinel, L., Doruk, N., Eskandari, G., & Oral, U. (2005). Liver and kidney toxicity in chronic use of opioids: An experimental long term treatment model. Journal of Biosciences, 30(2), 245-252.
Atici, S., Cinel, L., Cinel, I., Doruk, N., Aktekin, M., Akca, A., … Oral, U. (2004). Opioid neurotoxicity: Comparison of morphine and tramadol in an experimental rat model. International Journal of Neuroscience, 114(8), 1001-1011.
Bakker, M. K., Jentink, J., Vroom, F., Van Den Berg, P. B., De Walle, H. E., & De Jong-Van Den Berg, L. (2006). Maternal medicine: Drug prescription patterns before, during and after pregnancy for chronic, occasional and pregnancy-related drugs in The Netherlands. BJOG: An International Journal of Obstetrics & Gynaecology, 113(5), 559-568.
Bloor, M., Paech, M., & Kaye, R. (2012). Tramadol in pregnancy and lactation. International Journal of Obstetric Anesthesia, 21(2), 163-167.
Boasen, J. F., McPherson, R. J., Hays, S. L., Juul, S. E., & Gleason, C. A. (2009). Neonatal stress or morphine treatment alters adult mouse conditioned place preference. Neonatology, 95(3), 230-239.
Bravo, L., Mico, J. A., & Berrocoso, E. (2017). Discovery and development of tramadol for the treatment of pain. Expert Opinion on Drug Discovery, 12(12), 1281-1291.
Đanić, P., Salarić, I., & Macan, D. (2017). New findings on local tramadol use in oral surgery. Acta Stomatologica Croatica, 51(4), 336-344.
El-Wessemy, A. (2008). Histopathological and ultra-structural studies on the side effects of the analgesic drug tramadol on the liver of albino mice. Egyptian Journal of Zoology, 50, 423-442.
Fatima, S., Akhtar, M. F., Ashraf, K. M., Sharif, A., Saleem, A., Akhtar, B., … Ashraf, W. (2019). Antioxidant and alpha amylase inhibitory activities of Fumaria officinalis and its antidiabetic potential against alloxan induced diabetes. Cellular and Molecular Biology, 65(2), 50-57.
Gillen, C., Haurand, M., Kobelt, D. J., & Wnendt, S. (2000). Affinity, potency and efficacy of tramadol and its metabolites at the cloned human μ-opioid receptor. Naunyn-Schmiedeberg's Archives of Pharmacology, 362(2), 116-121.
Herrera, E., & Ortega-Senovilla, H. (2014). Lipid metabolism during pregnancy and its implications for fetal growth. Current Pharmaceutical Biotechnology, 15(1), 24-31.
Källén, B., & Reis, M. (2015). Use of tramadol in early pregnancy and congenital malformation risk. Reproductive Toxicology, 58, 246-251.
Lo, W., & Friedman, J. (2002). Teratogenicity of recently introduced medications in human pregnancy. Obstetrics & Gynecology, 100(3), 465-473.
Marquardt, K. A., Alsop, J. A., & Albertson, T. E. (2005). Tramadol exposures reported to statewide poison control system. Annals of Pharmacotherapy, 39(6), 1039-1044.
McLaughlin, P. J. (2002). Exposure to the opioid antagonist naltrexone throughout gestation alters postnatal heart development. Neonatology, 82(3), 207-216.
Motta, K., Gomes, P. R., Sulis, P. M., Bordin, S., & Rafacho, A. (2018). Dexamethasone administration during late gestation has no major impact on lipid metabolism, but reduces newborn survival rate in Wistar rats. Frontiers in Physiology, 9, 1-17.
Owoade, A., Adetutu, A., & Olorunnisola, O. (2019). Hematological and biochemical changes in blood, liver and kidney tissues under the effect of tramadol treatment. Journal of Alcoholism & Drug Dependence, 7(327), 2.
Polovina, M. M., Vukicevic, M., Banko, B., Lip, G. Y., & Potpara, T. S. (2017). Brugada syndrome: A general cardiologist's perspective. European Journal of Internal Medicine, 44, 19-27.
Rafati, A., Yasini, S. M., Dashti-Rahmatabadi, M. H., Pakdel, S., & Norani, F. (2006). Tramadol dependence rate as compared with morphine in rats. World Journal of Medicine and Medical Science, 1(1), 40-43.
Sabir, S., Akhtar, M. F., & Saleem, A. (2019). Endocrine disruption as an adverse effect of non-endocrine targeting pharmaceuticals. Environmental Science and Pollution Research, 26(2), 1277-1286.
Sabir, S., Saleem, A., Akhtar, M. F., Saleem, M., & Raza, M. (2018). Increasing beta cell mass to treat diabetes mellitus. Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University, 27(9), 1309-1315.
Sadler, T. W. (2011). Langman's medical embryology. North Central Avenue, Phoenix: Lippincott Williams & Wilkins.
Sahutoglu, C., Kocabas, S., & Askar, F. Z. (2018). Tramadol use in a patient with Brugada syndrome and morphine allergy: A case report. Journal of Pain Research, 11, 191-194.
Saleem, A., Saleem, M., Akhtar, M. F., Rasul, A., & Baig, M. M. F. A. (2020). Chemical characterisation, in vitro antioxidant, cytotoxicity and safety evaluation of Polystichum braunii (Spenn.) fee roots. Natural Product Research, 44(10), 1-6. https://doi.org/10.1080/14786419.2020.1797727
Saleem, A., Saleem, M., Akhtar, M. F., Shahzad, M., & Jahan, S. (2020a). Moringa rivae leaf extracts attenuate complete Freund's adjuvant-induced arthritis in Wistar rats via modulation of inflammatory and oxidative stress biomarkers. Inflammopharmacology, 28(1), 139-151.
Saleem, A., Saleem, M., Akhtar, M. F., Shahzad, M., & Jahan, S. (2020b). Polystichum braunii extracts inhibit complete Freund's adjuvant-induced arthritis via upregulation of I-κB, IL-4, and IL-10, downregulation of COX-2, PGE2, IL-1β, IL-6, NF-κB, and TNF-α, and subsiding oxidative stress. Inflammopharmacology, 28(6), 1633-1648.
Saleem, R., Iqbal, R., Abbas, M. N., Zahra, A., Iqbal, J., & Ansari, M. S. (2014). Effects of tramadol on histopathological and biochemical parameters in mice (Mus musculus) model. Global Journal of Pharmacology, 8(1), 14-19.
Schaefer, C., Peters, P. W., & Miller, R. K. (2014). Drugs during pregnancy and lactation: Treatment options and risk assessment. Cambridge, MA: Academic Press.
Schütter, A. F., Tünsmeyer, J., & Kästner, S. B. R. (2017). Influence of tramadol on acute thermal and mechanical cutaneous nociception in dogs. Veterinary Anaesthesia and Analgesia, 44(2), 309-316.
Šlamberová, R. (2012). Drugs in pregnancy: The effects on mother and her progeny. Physiological Research, 61, S123-S135.
Soetan, K., Akinrinde, A. & Ajibade, T. (2013). Preliminary studies on the haematological parameters of cockerels fed raw and processed guinea corn (Sorghum bicolor). Paper presented at the Proceedings of 38th Annual Conference of Nigerian Society for Animal Production.
Subedi, M., Bajaj, S., Kumar, M. S., & Mayur, Y. (2019). An overview of tramadol and its usage in pain management and future perspective. Biomedicine & Pharmacotherapy, 111, 443-451.
The HAPO Study Cooperative Research Group. (2008). Hyperglycemia and adverse pregnancy outcomes. New England Journal of Medicine, 358(19), 1991-2002.
Thompson, B. L., Levitt, P., & Stanwood, G. D. (2009). Prenatal exposure to drugs: Effects on brain development and implications for policy and education. Nature Reviews Neuroscience, 10(4), 303-312.
Van Gelder, M. M., Van Rooij, I. A., Miller, R. K., Zielhuis, G. A., de Jong-van den Berg, L. T., & Roeleveld, N. (2010). Teratogenic mechanisms of medical drugs. Human Reproduction Update, 16(4), 378-394.
Wise, L. D. (2016). Numeric estimates of teratogenic severity from embryo-fetal developmental toxicity studies. Birth Defects Research Part B: Developmental and Reproductive Toxicology, 107(1), 60-70.
Zulfqar, F., Akhtar, M. F., Saleem, A., Sharif, A., Akhtar, B., & Saleem, U. (2020). Chemical characterization, antioxidant evaluation, and antidiabetic potential of Pinus gerardiana (pine nuts) extracts. Journal of Food Biochemistry, 44, 1-12.