Nitric Oxide Mediation in Hydroxyurea and Nitric Oxide Metabolites' Inhibition of Erythroid Progenitor Growth.

ABSTRACT: In several systems, hydroxyurea has been shown to trigger nitric oxide (NO) release or activation of NO synthase (NOS). To elucidate this duality in its pharmacological effects, during myelosuppression, we individually examined hydroxyurea's (NO releasing agent) and NO metabolites' (stable NO degradation products) effects on erythroid colony growth and NOS/NO levels in mice using NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Hydroxyurea and nitrite/nitrate decreased the bone marrow cellularity that was blocked by PTIO only for the NO metabolites. Hydroxyurea inhibition of colony-forming unit-erythroid (CFU-E) formation and reticulocytes was reversed by PTIO. Moreover, hydroxyurea, through a negative feedback mechanism, reduced inducible NOS (iNOS) expressing c

SUBMITTER: Suboticki T 

PROVIDER: S-EPMC8616001 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature