An Animal Model for Assessing the Effects of Hydroxyurea Exposure Suggests That the Administration of This Agent to Pregnant Women and Young Infants May Not Be as Safe as We Thought

Int J Mol Sci. 2018 Dec 11;19(12):3986. doi: 10.3390/ijms19123986.

Abstract

The cytostatic agent hydroxyurea (HU) has proven to be beneficial for a variety of conditions in the disciplines of oncology, hematology, infectious disease and dermatology. It disrupts the S phase of the cell cycle by inhibiting the ribonucleotide reductase enzyme, thus blocking the transformation of ribonucleotides into deoxyribonucleotides, a rate limiting step in DNA synthesis. HU is listed as an essential medicine by the World Health Organization. Several studies have indicated that HU is well tolerated and safe in pregnant women and very young pediatric patients. To our knowledge, only a few controlled studies on the adverse effects of HU therapy have been done in humans. Despite this, the prevalence of central nervous system abnormalities, including ischemic lesions and stenosis have been reported. This review will summarize and present the effects of HU exposure on the prenatal and perinatal development of the rat cerebellar cortex and deep cerebellar nuclei neurons. Our results call for the necessity to better understand HU effects and define the administration of this drug to gestating women and young pediatric patients.

Keywords: apoptosis; cell death; cerebellum; electron microscopy; hydroxyurea; immunohistochemistry; neuron.

Publication types

  • Review

MeSH terms

  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Death / drug effects
  • Cerebellum / drug effects
  • Female
  • Humans
  • Hydroxyurea / adverse effects*
  • Immunohistochemistry
  • Infant, Newborn
  • Microscopy, Electron
  • Pregnancy

Substances

  • Hydroxyurea