Prenatal treatment with metronidazole induces cerebellar folia alteration in guinea pig fetuses

Authors

  • Ivan Đ. Čapo 1. Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad; 2. Center for Medical and Pharmaceutical Investigations and Quality Control, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad http://orcid.org/0000-0001-7531-5099
  • Ivan J. Milenković Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna https://orcid.org/0000-0001-7531-5099
  • Nataša P. Čapo 1. Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad; 2. Oncology Institute of Vojvodina, Put doktora Goldmana, 21204 Sremska Kamenica https://orcid.org/0000-0001-7547-222X
  • Nebojša P. Stilinović Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad https://orcid.org/0000-0003-0118-9418
  • Saša N. Vukmirović Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad https://orcid.org/0000-0002-3271-4492
  • Branislava D. Teofilović Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad https://orcid.org/0000-0002-0917-3974
  • Branka B. Petković Department of Neurophysiology, Institute for Biological Research “Siniša Stanković” - National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade https://orcid.org/0000-0001-7817-4092
  • Slobodan R. Sekulić Department of Neurology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad https://orcid.org/0000-0001-7889-310X

DOI:

https://doi.org/10.2298/ABS200619041C

Keywords:

metronidazole, neurotoxicity, neuronal migration, cerebellum, foliation

Abstract

Paper description:

  • The neurotoxic side effect of metronidazole in therapy of adults is established but there is insufficient data about the prenatal consequences of metronidazole treatment.
  • Pathohistological techniques were used to study the effect of metronidazole on guinea pig fetuses.
  • Metronidazole caused cell depletion in proliferative zones of the cerebellum and decrease of the areal fraction value in all cortical layers, as well as intensive folia alteration.
  • The presented results question the use of metronidazole during pregnancy.

Abstract: The most sensitive period in brain development is during prenatal life. The use of antibiotics in pregnancy is still controversial. Recent studies revealed the high neurotoxic potential of the antibiotic and antiprotozoal medication, metronidazole. However, there are insufficient data from animal studies about prenatal treatment effects. We investigated the effect of prenatal treatment with metronidazole on cerebellar development in guinea pigs. Treatment with metronidazole was performed from the 42nd to the 49th day of gestation. On the 50th day of pregnancy, all dams were killed, and the cerebella of the fetuses were analyzed. Gross cerebellar changes characterized by malposition of the folia with partial atrophy were found in 12 of 19 fetuses in the experimental group, but in none of 20 control fetuses that received saline. The most affected were folia VII with depletion of the areal fraction of the external granular layer, molecular layer and the internal granular layer. Purkinje cells displayed cell distortion with loss of normal dendritic polarity. The investigation revealed cell depletion, with a disturbance of the cytoarchitectonic of the cerebellar cortex and folia alteration.

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Published

2020-12-25

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1.
Čapo I Đ., Milenković IJ, Čapo NP, Stilinović NP, Vukmirović SN, Teofilović BD, Petković BB, Sekulić SR. Prenatal treatment with metronidazole induces cerebellar folia alteration in guinea pig fetuses. Arch Biol Sci [Internet]. 2020Dec.25 [cited 2024Dec.22];72(4):473-82. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/6035

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Vol. 72 No. 4 (2020)

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