Blood pressure, hematologic and biochemical changes following L-arginine supplementation in children with sickle cell anaemia already on hydroxyurea therapy.


Hydroxyurea is an approved therapy in the management of children suffering from sickle cell disease (SCD). In adults co-administration of hydroxyurea and L-Arginine in adult sufferers of SCD had shown some benefits. This study examined the effect of co-administration of hydroxyurea (15-35mg/kg/day) and L-Arginine (500 mg/day) for 6 weeks on blood pressure, haematological parameters, liver and antioxidant enzymes levels. The levels of these parameters when the subjects were on hydroxyurea alone were taken as control values. Results showed that the combined therapy (HU + L-Arginine) decreased SBP, DBP, MAP and PP (p <0.01 in each case) but increased %HbF, Hb and PCV (p< o.001 in each case). It elevated CAT, SOD, GPX (p < 0.001 in each case) but depressed MDA, AST, ALT and ALP (p < 0.001 in each case). The study shows that L-Arginine used as an adjunct to hydroxyurea therapy may be beneficial to children suffering from sickle cell anaemia

Click to view file (PDF)


Agrawal, R. K., Patel, R. K., Shah, V., Nainiwal, L. and Trivedi, B. (2014). Hydroxyurea in sickle cell disease: Drug Review. Indian J. Hematol. Blood Transfus. 30(2): 91–96.

Ajayi, I. O., Nwokocha, C. R. and Ebeigbe, A. B. (2013). Blood pressure variations in subjects with different haemoglobin genotypes. J. Afr. Ass. Physiol. Sci. 1: 23-26.

Akohoue, S.A., Shankar, S., Milne, G.L., Morrow, J., Chen, K. Y., Ajayi, W. U. and Buchowski M. S. (2007). Energy expenditure, inflammation, and oxidative stress in steady-state adolescents with sickle cell anemia. Pediatr. Res. 61: 233–238.

Atweh, G. F. and Schechter, A.N. (2001). Pharmacological induction of fetal hemoglobin: raising the therapeutic bar in sickle cell disease. Curr. Opin. Hematol. 8: 123–130.

Bakshi, N. and Morris, C. R. (2016). The role of the arginine metabolome in pain: implications for sickle cell disease. J. Pain Res. 9: 167–175

Carden, M. A. and Little, J. (2019). Emerging disease-modifying therapies for sickle cell disease. Haematologica 104(9): 1710-1719.

Dacie, J. V. and Lewis SM. (1991). Practical Hematology. 7th Ed Edinburgh, Churchill Livingstone.

Dasgupta, T., Hebbel, R. P. and Kaul, D. K. (2006). Protective effect of arginine on oxidative stress in transgenic sickle mouse models. Free Radical Biol. Med. 41: 1771– 1780.

Diallo, D. and Tchernia, G. (2002). Sickle cell disease in Africa. Curr. Opin. Hematol. 9: 111-116

Eleuterio, R. M. N., Nascimento, F. O., Araújo, T. G., Castro, M. F., Almeida-Filho, T.P., Maia-Filho, P. A., Eleuterio, J., Elias, D. B. and Lemes, R. P. (2019). Double-blind clinical trial of arginine supplementation in the treatment of adult patients with sickle cell anaemia. Adv. Hematol. Article ID 4397150, 6 pages.

Ellman, G. (1959). Tissues sulphydryl groups. Arch. Biochem. Biophysics 82: 70-77.

Hebbel, R. P., Osarogiagbon, D. and Kaul, D.K. (2004). The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy. Microcirculation. 11: 129–151.

Hebbel, R. P., Vercellotti, G. M. and Natth, K. A. (2009). A system biology consideration of the vasculopathy of sickle cell anaemia: the need for multi-modality chemoprophylaxis. Cardiovasc. Hematol. Disord. Drug Targets 9: 271–292.

Hussain, A. A. and Hassan, M. K. (2017). Blood pressure of children and adolescents with sickle cell anemia in Basra. Iraq Iranian J. blood & Cancer 9: 101-107.

Ingram, V. M. (1956). A specific chemical difference between the globins of normal human and sickle-cell anemia haemoglobin. Nature 178: 792–794.

Jaja, S. I., Ogungbemi, S. O., Kehinde, M. O. and Anigbogu, C. N. (2016). Supplementation with l-arginine stabilizes plasma arginine and nitric oxide metabolites, suppresses elevated liver enzymes and peroxidation in sickle cell anaemia. Pathophysiol. 23: 81–85.

Jaja, S. I., Kehinde, M. O., Olowoyeye, O. A., Shoneye, K.O., Tubi, O. O. and Adekunle, O. M. (2013). Vitamin C increases catalase but decreases liver enzymes and lipid peroxidation in sickle cell anemia subjects in the steady state. Nig. Qt. J. Hosp. Med. 23: 232-236.

Kaul, D. K. and Hebbel, R.P. (2000). Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice. J. Clin. Invest. 106: 411–420.

Kotila, T., Adedapo, K., Adedapo, A., Oluwasola, O., Fakunle, E. and Brown B. (2005). Liver dysfunction in steady state sickle cell disease, Ann. Hepatol. 4: 261–263.

Little, J. A., Hauser, K. P., Martyr, S.E., Harris, A., Maric, I., Morris, C.R., Suh, J. H., Taylor, J., Castro, O., Machado, R., Kato, J. and Gladwin, M. T. (2009). Hematologic, biochemical, and cardiopulmonary effects of l-arginine supplementation or phosphodiesterase 5 inhibition in patients with sickle cell disease who are on hydroxyurea therapy. Eur. J. Haematol. 82: 315–321.

McGann, P. T. and Ware, R. E. (2015). Hydroxyurea therapy for sickle cell anemia. Expert Opin. Drug Saf. 14(11): 1749 – 1758.

Morris, C. R., Morris, S. M., Hagar, W., van Warmerdam, J., Claster, S., Kepka-Lenhart D., Machado, L., Kuypers, F. A. and Vichinsky, E. P. (2003). Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am. J. Resp. Crit. Care Med. 168: 63–69.

Nsiah, K., Dzogbefia, V. P., Ansong, D., Akoto, A. O., Boateng, H. and Ocloo, D. (2011). Pattern of AST and ALT changes in relation to hemolysis in sickle cell disease. Clin. Med. Insight Blood Disord. 4: 1–9.

Nur, E., Biemond, B. J., Otten, H., Brandjes, D. P., John-John, B. and Schnog, J. B. (2011). Oxidative stress in sickle cell disease; pathophysiology and potential implications for disease management. Am. J. Hematol. 86: 484–489.

Ogungbemi, S. I., Anigbogu, C. N., Kehinde, M. O. and Jaja, S. I. (2013). L-arginine increases nitric oxide and attenuates pressor and heart rate responses to change in posture in sickle cell anemia subjects. Niger. J. Physiol. Sci. 28: 045 –050.

Pauling, L., Itano, H. A., Singer, S.J. and Wells, I. C. (1949). Sickle cell anemia a molecular disease. Science 110: 543-548.

Piel, F. B., Patil, A. P., Howes, R.E., Nyangiri, O. A., Gething, P. E., Dewi, M., Temperley, W. H., Williams, T. N., Weatherall, D. J. and Hay, S. I. (2013). Global epidemiology of sickle haemoglobin in neonates: a contemporary geosttistical model-based map and population estimates. Lancet 381: 142–151.

Raghupathy, R. and Billett, H. (2009). Promising therapies in sickle cell disease. Cardiovasc. Hematol. Disord. Drug Targets. 9: 1–8.

Reiter, C.D., Wang, X., Tanus-Santos, J.E., Hogg, N., Cannon, R.O. and Schecheter, A.N. (2002). Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat. Med. 8: 1383–1389.

Rodgers, G. P., Dover, G. J., Uyesaka, N., Noguchi, C. T., Schechter, A.N. and Nienhuis, A.W. (1993). Augmentation by erythropoietin of the fetal-hemoglobin response to hydroxyurea in sickle cell disease. New Eng. J. Med. 328: 73–80.

Rukkumani, R., Aruna, K., Varma, P. S., Rajasekaran, K.N . and Menon, V. P. (2004). Comparative effects of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative stress. J. Pharm. Pharmaceutical Sci. 7: 274-283.

Saborio, P. and Scheinman, J. I. (1999). Sickle cell nephropathy. J. Am. Soc. Nephrol. 10: 187-192.

Titus, J., Chari, S., Gupta, M. and Parekh, N. (2004). Pro-oxidant and anti-oxidant status in patients of sickle cell anemia. Ind. J. Clin. Biochem. 19: 168-172.

Umar, A., Mustafa, A. and Muuta, I. (2016). Prevalence of elevated blood pressure among primary school children in Kano Metropolis, Nigeria. Nig. J. Cardiol. 13: 57-61.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Copyright (c) 2021 Array