2003, Number 4
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Bioquimia 2003; 28 (4)
Antisickling agent vanillin
Toro GG, Falcón DJE, Alonso GY, Valdés RYC, Cabal MCA
Language: Spanish
References: 31
Page: 4-10
PDF size: 320.14 Kb.
ABSTRACT
The desoxyhemoglobin S polymerization, characterized by
the delay time or nucleation, constitutes the primary
physiopathologic event of the sickle cell disease. An effective
treatment doesn’t still exist and they are studied compound
that inhibit the hemoglobin S polymerization and the red cell
sickling. The moderate antisickling activity of a food additive
4-hydroxy-3-methoxybenzaldehyde (vanillin), at 1:4, 1:5, 1:6,
1:7 and 1:8 molar ratio (hemoglobin:vanillin), it was evaluated
in vitro by means of their effect on the delay time using the
Proton Nuclear Magnetic Resonance (RMN-1H). To specify
the absence of cytotoxic activity of the vanillin on sickle red
blood cells it was evaluated the effect of the molar ratios
(1:1, 1:2, 1:4, 1:5, 1:8 and 1:10) on the hemoglobin liberation
and it was compared with normal red blood cells. The vanillin
increased the delay time and its variation percentage was
17±8% (1:4), 21±15% (1:5), 28±14% (1:6), 23±10% (1:7)
and 35±26% (1:8), being observed a dose dependent effect
on the retard of the polymerization. The test of multiple
comparison reported non significant differences among the
work concentrations (p>0.05). A low percentage of hemolysis
was obtained with a small increase for the molar ratio 1:10
when compared with the rest (p<0.05%). Although a tendency
was not obtained in the whole study; being demonstrated the
absence of cytotoxics effects for red blood cells, their target
of pharmacological action.
REFERENCES
Lehninger AL Bioquímica. Tomo I. Ciudad de la Habana:Editorial Pueblo y Educación; 1981. p. 150.
Eaton WA, Hofrichter J, Ross PD. Delay time of gelation:a possible determinant of clinical severity in sickle celldisease. Blood 1976; 47: 621-627.
Císcar F, Farreras P. Diagnóstico Hematológico. Tomo IIBarcelona: Editorial JIMS; 1972. p. 1387-1388, 1390,1422-1426.
Dean J and Schechter AN. Sickle cell anemia: molecularand cellular bases of therapeutic approaches. N Engl JMed 1978; 299: 752-763, 804-811, 863-870.
Serjeant GR. Sickle Cell Disease. 2nd ed. Great Britain:Oxford Medical Publications; 1992. p. 56, 61, 71-77,120-366.
Colombo B, Guerchicoff E, Martínez G. Genética y clíni-ca de las hemoglobinas humanas. 1a ed. Habana: Edito-rial Pueblo y Educación; 1993. p. 146-195.
Espinosa E. La anemia drepanocítica en Cuba. Experien-cia de 30 años. Rev Cub Hematol Inmunol Hemot 1996;12: 97-105.
Eaton WA and Hofrichter J. Hemoglobin S gelation andsickle cell disease. Blood 1987; 70: 1245-1266.
Eaton WA and Hofrichter J. Sickle cell hemoglobinpolymerization Adv Protein Chem 1990; 40: 67-68, 80-110, 157-175.
Kaperonis AA, Handley DA, Chien S. Fibers, Crystalsand other forms of HbS polymers in deoxygenated sickleerythrocytes. Am J Hematol 1986; 21: 269-275.
Rodgers DW, Crepeau RH and Edelstein SJ. Pairings andpolarities of the 14 strands in sickle cell hemoglobinfibers. Proc Natl Acad Sci 1987; 84: 6157-6161.
Xianfeng Li. Mutational analysis of sickle haemoglobin (Hb)gelation. Biotechnol Appl Biochem 1999; 29: 165-184.
Losada J, Guilart F, Cabal CA. NMR relaxation study ofsickle cell disease. Proceedings of the XXIV AMPERECongress Magnetic Resonance and Related Phenomena:Poznañ; 1988.p. 1027-1030.
Zaugg RM, Walder JA and Klotz IM. Schiff base aductsof hemoglobin. J Biol Chem 1977; 252: 8542-8548.
Beddell CR, Kneen G, White RD. The antisickling activityof a series of aromatic aldehydes. Br J Pharmacol 1979;66: 70.
Abraham DJ, Mehanna AS, Wireko FC, Whitney J,Thomas RP and Orringer EP. Vanillin, a potential agentfor the treatment of sickle cell anemia. Blood 1991; 77:1334-1341.
Abraham DJ. Design, synthesis and testing of potentialantisickling agents. 1. Halogenated benzyloxy andphenoxy acids. J Med Chem 1982; 25: 1015-1017.
Abraham DJ. Design, synthesis and testing of potentialantisickling agents. 4. Structure-activity relationships ofbenzyloxy and phenoxy acids. J Med Chem 1984; 27:967-978.
Merret ME, Stammers DK, White RD, Wootton R, KneenG. Characterization of the binding of the antisicklingcompound, BW12C, to haemoglobin. Biochem J 1986;239: 387-392.
Orringer EP, Blythe DS, Whitney JA, Brockenbrough S,Abraham DJ. Physiologic and rheologic effects of theantisickling agent ethacrynic acid and its N-butilatedderivative on normal and sickle erythrocytes. Am JHematol 1992; 30: 39-44.
Alvarez ED, Cabal CA, Fernández AA, Soler C, Lores M,Del Toro G. IE-HPLC and NMR relaxometry demonstratea potential roll for vanillin in sickle cell disease. AvanBiotec Mod 1997; 4: E6.
Abdala JC, Soler C, Fernández AA, Alvarez ED, Del ToroG. Estudio de la interacción de compuestos carboniloscon hemoglobinas in vitro. Valoración de su efectoantisickling. Rev Cub Quim 1996; 8:3-10.
Del Toro G, Pozo AR, Rodríguez JC, Fernández AA,Soler C. Influencia del 4-hidroxi-3-metoxibenzaldehído(vainillina) en la polimerización de la hemoglobina S(HbS). Rev Cub Quim 2002; 14: 59-64.
Ohta T. Modification of genotoxicity by naturallyoccurring flavorings and their derivatives. Critical RevToxicol 1993; 23: 127-146.
Stanley HR. Toxicity testing of dental materials. 1st ed.Florida: CRC Press Inc; 1985. p.17-22.
Bailey K, Morris JS, Thomas P, Serjeant GR. Fetalhaemoglobin and early manifestations of homozygoussickle cell disease. Arch Dis Child 1992; 67: 517-520.
Nagel RL, Bookchin RM, Johnson J, Labie D, WajcmanH, Isaac-Sodeye WA, et al. Structural bases of theinhibitory effects of hemoglobin F and hemoglobin A2on the polymerization of hemoglobin S. Proc Natl AcadSci USA 1970; 76: 670-672.
Rodgers GP. Pharmacologic modulation of fetalhemoglobin. Sickle cell disease: basic principles andclinical practice. 1st ed. New York: Raven Press, Ltd; 1994.p. 829-843.
Bun HF. Induction of fetal hemoglobin in sickle celldisease. Blood 1999; 93:1787-1789.
Mohandas N and Evans E. Adherence of sickleerythrocytes to vascular endothelial cell: Requirementfor both cell membrane changes and plasma factors. Blood1984; 64:282-287.
Ballas S and Smith ED. Red blood cell changes during theevolution of the sickle cell painful crisis. Blood 1992;79:2154-2163.
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