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.
Highlights
Hydroxyurea (HU) is an inhibitor of the ribonucleotide reductase enzyme
The cerebellar cortex is formed by three layers: The molecular layer (ML), whose neuronal components include stellate and basket neurons; the Purkinje cell layer, that contains Purkinje cells (PCs) and candelabrum cells; and the granule layer, that consists of granule cells (GCs), Golgi cells, unipolar brush cells and Lugaro cells [58,59]
As our studies have revealed that HU-exposure induces apoptosis in the developing cerebellum, we examined whether the damaged of external granule cell (EGL) cells can lead to the activation of microglial cells
Summary
Hydroxyurea (HU) is an inhibitor of the ribonucleotide reductase enzyme It impairs DNA synthesis in a wide variety of cells and organisms, including Saccharomyces cerevisiae [1]. In perinatal life on the other hand, cerebellar external granule cell (EGL) depletion and the ectopic location of granule cells (GCs) due to the HU exposure have been reported [10,11]. Despite these results, the influence of this agent on the development of the rat cerebellum has not been completely elucidated. Animals were treated with HU during their perinatal stage of life and killed at appropriate times, ranging from 6 to 48 h after treatment administration or later once they had reached adulthood
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