An update on arginine in sickle cell disease

ABSTRACT

Introduction: Recent knowledge on the pathophysiology of sickle cell disease (SCD) have emphasized the role of hemolysis and nitric oxide (NO) depletion on the occurrence of acute and chronic complications. This new paradigm raises the possibility of innovative therapeutic approaches, including arginine supplementation.

Areas covered: This review comments on the role of NO in the regulation of vascular tone, as well as its impaired metabolism in hemolytic diseases. Disturbances in these processes in SCD were detailed considering the functions of endothelial nitric oxide synthase (eNOS), arginase and asymmetric dimethylarginine (ADMA). Therapeutic approaches involving these pathways were discussed with emphasis on the effects of arginine therapy on the normalization of NO levels and its consequent clinical effects, mainly the decrease in the intensity of vaso-occlusive crises.

Expert opinion: Considering the complex pathogenesis of the disease and the restricted access to curative therapies, the management of SCD must rely on a combination of therapies covering multiple pathways. Arginine supplementation, a low-cost approach, has shown promising results, which is particulary important considering most of the affected patients still live in unfavorable socioeconomic conditions. These findings should encourage further clinical trials, evaluating other outcomes and specific subpopulations, such as adult patients and compound heterozygotes.

KEYWORDS:

• Arginine
• nitric oxide
• hemolysis
• sickle cell disease

Article Highlights

• Scavenge of nitric oxide (NO) by free hemoglobin and release of intra-erythrocyte arginase are mechanisms involved in the pathology of hemolytic disorders

• Targeting NO metabolism in Sickle Cell Anemia represents an interesting way of preventing or attenuating the endothelial damage characteristic of the disease

• Arginine supplementation has shown promising results in this setting, evidenced by increased plasma NO bioavailability and decreased intensity of vaso-occlusive crises

• The association of arginine with Hydroxyurea and L-glutamine may reveal the benefits of a multi-pathway approach

• Future studies are still needed to assess the role of this approach also for attenuating chronic complications of the disease

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.