Hydroxyurea and arginine therapy: impact on nitric oxide production in sickle cell disease
| Autor: | Elliott Vichinsky, Frans A. Kuypers, Diane Kepka-Lenhart, Lorenzo Machado, Jane Van Warmerdam, Sidney M. Morris, Claudia R. Morris |
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| Rok vydání: | 2003 |
| Předmět: |
Hemolytic anemia
Adult Male medicine.medical_specialty Arginine Adolescent Metabolite Vasodilation Antineoplastic Agents Anemia Sickle Cell Nitric Oxide Nitric oxide chemistry.chemical_compound Internal medicine medicine Humans Hydroxyurea Drug Interactions Child biology business.industry Hematology Free Radical Scavengers medicine.disease Sickle cell anemia Arginase Nitric oxide synthase Endocrinology Oncology chemistry Biochemistry Pediatrics Perinatology and Child Health biology.protein Drug Therapy Combination Female business |
| Zdroj: | Journal of pediatric hematology/oncology. 25(8) |
| ISSN: | 1077-4114 |
| Popis: | Purpose: Recent data suggest that hydroxyurea (HU) increases the production of nitric oxide (NO), a potent vasodilator. NO is normally metabolized from L-Arginine (Arg). However, in vitro and animal experiments suggest that HU is the NO donor itself. In contrast, a recent study indicates that nitric oxide synthase (NOS) may play a role. Since adults with sickle cell disease (SCD) are Arg-deficient, Arg availability may limit the ability of HU to maximally impact NO production if an NOS mechanism is involved. The authors have previously shown that Arg supplementation alone induces a paradoxical decrease in NO metabolite (NOx) production. Methods: The authors studied the effects of HU and Arg supplementation on NOx production. HU alone or HU + Arg was administered to patients with SCD at steady state, and sequential levels of Arg, serum NOx and exhaled NO were followed over 4 hours. Results: After HU + Arg, all patients demonstrated a significant increase in serum NOx production within 2 hours. When the same patients were treated with HU alone (5.1 ± 2 mol/L), a mixed response occurred. NOx levels increased in four patients and decreased in one patient (�23.3 mol/L). Conclusions: While Arg alone does not increase serum NOx production in SCD patients at steady state, it does when given together with HU. Hence, co-administration of Arg with HU may augment the NOx response in SCD and improve utilization of Arg in patients at steady state. |
| Databáze: | OpenAIRE |
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