Effect of azithromycin on fetal development in rats

  • Authors

    • Ashraf Elkomy professor of pharmacology
    • Asmaa M. Kandeil
    • Mohamed Abo-Salem
    • Wedad A. Hassan
    • Mohamed Aboubakr
    • Alzahraa A. Elhemiely
    2018-06-05
    https://doi.org/10.14419/ijpt.v6i1.11709
  • Rats, Pregnancy, Macrolides, Azithromycin, Teratology.
  • Abstract

    This study was designed to evaluate the potential risks of the Azithromycin administration on fetuses. Therefore pregnant rats were received Azithromycin orally (90 and 180 mg/kg b.wt, daily) from sixth day until the fifteenth day of gestation. At 20th day of gestation female sacrificed; abortion, fetal resorptions, visceral examination, skeletal examination, Oxidative stress markers and histopathological examination for fetuses were recorded. Azithromycin caused abortion, fetal resorptions, growth retardation, hematoma and paralysis of limbs. Also caused cerebral dilatation, microcephaly, perforation of hard palate and hemorrhage around internal organs. By skeletal examination; weak and incomplete ossification were observed in bones .Biochemical studies showed that Azithromycin administration resulted in decreased glutathione reduced but increased malonaldahyde compared to control groups. Fetal kidney revealed degeneration and necrosis in the tubular lining epithelium and fibrosis in between the atrophied renal tubules. This study supports and proofs the potential risks of the azithromycin administration on fetuses.

     

     

  • References

    1. [1] Abo-Kora S, El-Meleh A, Aboubakr M. (2016) Effect of Tilmicosin on Fetal Developments in Pregnant Female Albino Rats. Pharmacology & Pharmacy. 7(4) 4236.https://doi.org/10.4236/pp.2016.74019.

      [2] Aboubakr M, Elbadawy M, Soliman A, and El-Hewaity M. (2014) Embryotoxic and Teratogenic Effects of Norfloxacin in Pregnant Female Albino Rats. Advances in Pharmacological Sciences. doi:10.1155/2014/924706. https://doi.org/10.1155/2014/924706.

      [3] Barcellona, P.S.; Fancelli, O.; and Campana, A. (1977) Teratological study of etoperidone in the rat and rabbit. Toxicol. Eight: 87-94.https://doi.org/10.1016/0300-483X(77)90026-9.

      [4] Benjamin,B.; Orna, D.; Svetlana, S.; Rotem,T.;Judith, A.;Igor, F.; Matitiahu, B.; and Asher, O. (2008) Pregnancy outcome after gestational exposure to the new macrolides:A prospective multi-center observational study. Euro. J. ObstretGynecolReprodBiol.141; 31–34https://doi.org/10.1016/j.ejogrb.2008.07.008.

      [5] Beutler, E.; Duron, O.; and Kelly, B.M. (1963) Improved method for the determination of blood glutathione. J Lab Clin Med. 61:882-8.

      [6] Brent, R. L., & Fawcett, L. B. (2007) Developmental toxicology, drugs and fetal teratogenesis. Clinical Obstetrics. 261.

      [7] Elkomy A, Aboubakr M and Medhat N. (2016) some teratological effects of difloxacin in rats. Benha Veterinary Medical Journal. 30(1): 266-271.

      [8] Elsayed M, Elkomy A, Aboubakr M, and Morad M. (2014) Tissue Residues, Hematological and Biochemical Effects of Tilmicosin in Broiler Chicken. Veterinary Medicine International. doi:10.1155/2014/502872.https://doi.org/10.1155/2014/502872.

      [9] Farrag, AH,Hassan, BN, Ezz-Eldin D, Gabri MS, Kandil, AM. (2015) Histological and Immunohistochemical Studies on the Kidneys of Pregnant Rats Treated with Clarithromycin. The Egyptian Journal of Hospital Medicine.61:591-614.https://doi.org/10.12816/0018763.

      [10] Gabri, M.S.;Asmaa,M. K.;Maiada, M.;andNehad, M. (2015) Effect of clarithromycin administration during late gestational period on the pregnant albino rats and their fetuses.The Egyptian Journal of Hospital Medicine. 60.

      [11] Hayes, A.W. (1986) Principles and Methods of Toxicology. Student Edition, Raven Press, New York, 141-184.

      [12] Hracsko Z, Orvos H, Novak Z, Pal A, Varga IS. (2008) Evaluation of oxidative markers in neonates with intra uterinr growth retardation. Redox Report. 13:11-16.https://doi.org/10.1179/135100008X259097.

      [13] Inouye, M. (1976) Differential staining of cartilage and bone in fetal mouse skeleton by Alcianblue and Alizarin red-Congenital Anomalies. 16: 171-173.

      [14] Institute of Laboratory Animal Resources (1996) Guide for the Care and Use of Laboratory Animals, 8th edition. Washington, D.C.: National Academy Press.

      [15] Karabulut, A .K. Uysa, I. I.; Acar, H.; and Fazliogullari,H.(2008) Investigation of developmental toxicity and teratogenicity of macrolide antibiotics in cultured rat embryos. Anat. Histol. Embryol. 37, 369–375https://doi.org/10.1111/j.1439-0264.2008.00861.x.

      [16] Koren, G.; Pastuszak, A.; and Ito, S. (1998) Drugs in pregnancy. N Engl J Med. 338: 1128-37 https://doi.org/10.1056/NEJM199804163381607.

      [17] Maria, R.; Morten, L.; and Hedvig, N. (2012) Pregnancy outcome after gestational exposure to erythromycin – a population-based register study from Norway.British Journal of Clinical Pharmacology. 74: 1053–1062.https://doi.org/10.1111/j.1365-2125.2012.04286.x.

      [18] Marie, L.; Björn, P. P.; Rie, BS.; Bjarke F.; Camilla K.; Lars J Diaz .; Jan Wohlfahrt chief .; and Mads Melbye . (2014) Use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis: nationwide cohort study. BMJ; 348: 1908.https://doi.org/10.1136/bmj.g1908.

      [19] Paget, G.E. and Barnes, I.M. (1964) Interspecies dosage conversion scheme in evaluation of results and quantitative application in different species in (evaluation of drug activities: Pharmacometrics), Laurance, D.R. and Bachorach, A.L. (Edrs), Academic Press London and New York.; 1: 160-163.

      [20] Preeti,S.; Lubhan,S.; Sambhu,C. M.; Sokindra, K.; and Ishwari N.S. (2014) Erythromycin induced genotoxicity and hepatotoxicity in mice pups Treated during post gestation period. Fundamental and clinical pharmacology; 28: 519-529.https://doi.org/10.1111/fcp.12055.

      [21] Ramsey, P.S.; Vaules, M.B.; Vasdev, G.M.; Andrews,W.W .; and Ramin ,K.D. (2003) Maternal and transplacental pharmacokinetics of azithromycin. Am J Obstret Gynecol. 188:714–718?https://doi.org/10.1067/mob.2003.141.

      [22] Uchiyama M and Mihara M. (1978) Analytical biochemistry. 86, 271https://doi.org/10.1016/0003-2697(78)90342-1.

      [23] Meeraus WH, Petersen I, Gilbert R. (2015) Association between Antibiotic Prescribing in Pregnancy and CerebralPalsy or Epilepsy in Children Born at Term: A Cohort Study Using TheHealth Improvement Network.

  • Downloads

  • How to Cite

    Elkomy, A., M. Kandeil, A., Abo-Salem, M., A. Hassan, W., Aboubakr, M., & A. Elhemiely, A. (2018). Effect of azithromycin on fetal development in rats. International Journal of Pharmacology and Toxicology, 6(1), 18-23. https://doi.org/10.14419/ijpt.v6i1.11709

    Received date: 2018-04-18

    Accepted date: 2018-05-19

    Published date: 2018-06-05