Instasci Journal of Pharmaceutical Sciences Research Vol.2, issue 1, 2012 ISSN: 2277-6958 18 THE SYNERGISTIC EFFECT OF SOME ANTISICKLING AGENTS Nwaoguikpe RN*, Alisi CS, Ujowundu CO, Emejulu AA Department of Biochemistry, Federal University of Technology, Owerri, Imo State, Nigeria. *Corresponding author: coconacik@yahoo.com Manuscript No.: Instasci01202011. Available online at: www.instasci.info ©2012 Instasci Journals Abstract: The synergistic effect of some antisickling nutrients and amino acids was investigated to determine the possibility of combining antisickling agents to achieve enhancement or potentiation. The approach involved the use of amino acids and other nutrients whose antisickling effectiveness have been documented. These were combined and the effect of such combination assessed on some antisickling parameters such as sickle cell hemoglobin polymerization inhibition, sickle cell reversion experiment, Fe 2+ /Fe 3+ ratio of HbSS blood and their action on lactate dehydrogenase (LDH) activity of sickle cell blood. Results from the hemoglobin polymerization assay revealed the relative % inhibition for the following: L-Phe (83.30), L-Serine (76.40), L-Arg(91.70), L-Lys (84.80) and Ascorbate (88.90), but when combined with equimolar/intimate concentrations of other amino acids and vitamins at a final assay concentration of 200μM; results indicated an improvement over the previous result as follows: L-Phe + Vit.C (93.10), Phe+Ser (93.10)and others having the same value. Even the intimate mixtures of Phe+Ser+Arg+Lys+Vit C had the same value of 93.10. For the sickle cell reversion experiment, the time required to revert 50% sickle cell to normal erythrocytes has the sequence: 30s,36s,28s,32s,38s,28s,25s,26s,25s and 26s for Phe, Ser, Arg, Lys, Vit.C , Phe +Ser, Phe+ Arg, Phe+Lys, Phe +Vit.C, Phe +Lys+Vit C+ Ser + Arg respectively. There is a gradation of improvement in the Fe 2+ /Fe 3+ ratio from the single amino acid antisickling agents to the longer polypeptide/ additive combinations which ranged from 17.82 % increase in ratio for L-Phe to 107.29 for Phe+ Ser+ Lys + Arg+Vit C. The effect of the additive principle on serum LDH activity was very outstanding. The antisickling agents were able to reduce the LDH activity from 29.60 % for L- Phe to 45.34 % for the Phe+Ser+Lys+Arg Vit C combination. The synergistic effect of antisickling agents has been the current approach adopted in the design of effective antisickling agents and other conventional drugs used in the treatment of many malignant syndromes similar to sickle cell disease (SCD).as this combination proved more efficacious than the single antisickling agent protocol. Key words: Sickle cell disease, synergism, antisickling agents, amino acids, vitamins. A homozygous mutation of the β-globin, a subunit of adult hemoglobin A (HbA), is the proximate cause of sickle cell disease (SCD).Sickle hemoglobin (HbS) shows peculiar biochemical properties which lead to polymerization when deoxygenated. HbS polymerization is associated with a reduction in cell ion and water content (cell dehydration), increased cell density which further accelerates HbS production 1 .Pathophysiological studies have shown that dense dehydrated red cells may play a central role in acute and chronic manifestations of sickle cell disease in which intravascular sickling in capillaries and small vessels lead to vaso-occlusive episodes, resulting in impaired blood flow in a variety of organs and tissues. Vaso-occlusive events in the micro-circulation results from a complex scenario involving interactions between different cell types ,including dense dehydrated sickle cells, reticulocytes, abnormally activated endothelial cells, platelets and plasma factors, such as cytokines and oxidized pro-inflammatory lipids 2,3 . Antisickling agents are nutrients, drugs, phytochemicals and ions which by their actions inhibit the pathphysiological mechanisms INTRODUCTION