La esterificación de ácido oleico en policosanoles aumenta su biodisponibilidad y el efecto hipocolesterolémico en ratas

Autores/as

  • D. Haim Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile - Faculty of Medicine, University of the Andes
  • A. Valenzuela Laboratory of Lipids and Antioxidants, Institute of Nutrition and Food Technology, University of Chile - Faculty of Medicine, University of the Andes
  • M. C. Brañes Naturalis S.A.
  • M. Fuenzalida Naturalis S.A.
  • L. A. Videla Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile

DOI:

https://doi.org/10.3989/gya.010612

Palabras clave:

Absorción de Policosanoles, Biodisponibilidad, Efecto reductor de colesterol, Octacosanol, Policosanol, Triacontanol, Ratas

Resumen


Los Policosanoles están formados por una mezcla de alcoholes alifáticos de cadena larga y se obtienen de las ceras de la caña de azúcar. Más de cincuenta estudios indican que los policosanoles reducen el colesterol sérico, mientras que otros no logran reproducir este efecto. El objetivo de esta investigación fue evaluar la biodisponibilidad de policosanoles esterificados y no esterificados (NEP), en relación con sus efectos hipocolesterolémicos. Para ello, a ratas Sprague Dawley se les administró una dosis oral diaria de 100 mg kg–1 de NEP, 117 mg kg–1 de policosanoles esterificados con ácido butírico (BAEP), ó 164 mg kg–1 de policosanoles esterificados con ácido oleico (OAEP). La absorción de los policosanoles se evaluó en el plasma entre 0 y 3 horas después de la ingestión. Para evaluar los cambios en el colesterol total, colesterol-LDL, colesterol-HDL y triglicéridos en el plasma y en la fosforilación de la hígado 3-hidroxi-3-metilglutaril coenzima A reductasa (HMG-CoA red), la ingesta de las ratas fue suplementada con policosanoles no esterificados o esterificados durante 5 semanas. Los resultados indicaron que la absorción de los policosanoles fue significativamente mayor en las ratas tratadas con los OAEP que en las sometidas a los NEP o las que se les administró BAEP. Los OAEP redujeron significativamente el colesterol plasmático total y el colesterol- LDL de las ratas, además de aumentar 5.6 veces (P < 0,05) sobre los valores control, en el contenido hepático de la HMG-CoA fosforilada red. En conclusión, la esterificación de policosanoles con ácido oleico aumenta la biodisponibilidad de los policosanoles, y mejora significativamente el perfil de lípidos séricos en ratas normocolesterolémicos en asociación con la inactivación de la colesterogénesis control HMG-CoA red.

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Citas

Arruzazabala ML, Noa M, Menéndez R, Mas R, Carbajal D, Valdes S, Molina V. 2000. Protective effect of policosanol on atherosclerotic lesions in rabbits with exogenous hypercholesterolemia. Braz. J. Med. Biol. Res. 33, 835-840. http://dx.doi.org/10.1590/S0100-879X2000000700015 PMid:10881060

Batista J, Stusser R, Saez F, Pérez B. 1996. Effect of policosanol on hyperlipidemia and coronary heart disease in middle-aged patients. A 14-month pilot study. Int. J. Clin. Pharmacol. Ther. 34, 134-137. PMid:8705091

Berthold H, Unverdoeben S, Degenhardt R, Bulitta M, Gouni-Berthold I. 2006. Effect of lipids policosanol on lipid levels among with hypercholesterolemia or combined hyperlipidemia. JAMA. 295, 2262-2269. http://dx.doi.org/10.1001/jama.295.19.2262 PMid:16705107

Brockerhoff H. 1970. Substrate specificity of pancreatic lipase: Influence of the structure of fatty acids on the reactivity of esters. Biochim. Biophys. Acta. 212, 92-101. http://dx.doi.org/10.1016/0005-2744(70)90181-6

Buhman KK, Accad M, Novak S, Choi RS, Wong JS, Hamilton RL, Turley S, Farese RV Jr. 2000. Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat. Med. 6, 1341-1347. http://dx.doi.org/10.1038/82153 PMid:11100118

Castaño G, Mas R, Arruzazabala ML, Noa M, Illnait J,Fernandez JC, Molina V, Menendez A. 1999. Effects of policosanol and pravastatin on lipid profile, platelet aggregation and endothelemia in older hypercholesterolemic patients. Int. J. Clin. Pharm. Res. 19, 105-116. PMid:10939028

Castaño G, Mas R, Fernández L, Fernández JC, Illnait J, López LE, Alvarez E. 2000. Effects of policosanol on postmenopausal women with type II hypercholesterolemia. Gynecol. Endocrinol. 14, 187-195. http://dx.doi.org/10.3109/09513590009167681 PMid:10923280

Castaño G, Mas R, Fernández L, Illnait J, Gámez R, Alvarez E. 2001. Effects of policosanol 20 versus 40 mg/day in the treatment of patients with type II hypercholesterolemia: a 6-month double-blind study. Int. J. Clin. Pharmacol. Res. 21, 43-57. PMid:11708574

Castaño G, Mas R, Fernández L, Illnait J, López E, Gamez R, Mendoza S, Fernández J, Mesa M. 2003. Effects of D-003 on the lipid profile of patients with type II hypercholesterolemia: a phase II clinical study. Clin. Drug Investig. 23, 789-802. PMid:17536893

Choudhury N, Tan L, Truswell AS. 1995. Comparison of palmolein and olive oil: effects on plasma lipids and vitamin E in young adults. Am. J. Clin. Nutr. 61, 1043-1051. PMid:7733026

Clifton P. 2009. Lowering cholesterol - a review on the role of plant sterols. Aust. Fam. Physician 38, 218-221. PMid:19350071

Crespo N, Illnait J, Mas R, Fernández L, Fernández JC, Castaño G. 1999. Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. Int. J. Clin. Pharmacol. Res. 29, 117-127.

Dulin M, Hatcher L, Sasse H, Barringer T. 2006. Policosanol is ineffective in the treatment of hypercholesterolemia: a randomized controlled. Am. J. Clin. Nutr. 84, 1543–1548. PMid:17158441

Francini-Pesenti F, Brocadello F, Beltramolli D, Nardi M, Caregaro L. 2008a. Sugar cane policosanol failed to lower plasma cholesterol in primitive, diet-resistant hypercholesterolaemia: a double blind, controlled study. Complement Ther. Med. 16, 61-65. http://dx.doi.org/10.1016/j.ctim.2007.08.003 PMid:18514906

Francini-Pesenti F, Beltramolli D, Dall'acqua S, Brocadello F. 2008b. Effect of sugar cane policosanol on lipid profile in primary hypercholesterolemia. Phytother. Res. 22, 318-322. http://dx.doi.org/10.1002/ptr.2315 PMid:18167048

González-Bravo L, Magraner-Hernández J, Acosta-Gonzalez PC, Pérez-Souto N. 1996. Analytical procedure for the determination of 1-octacosanol in plasma by solvent extraction and capillary gas chromatography. J. Chromatogr. B Biomed. Appl. 682, 359-363. http://dx.doi.org/10.1016/0378-4347(95)00515-3

Gouni-Berthold I, Berthold HK. 2002. Policosanol: clinical pharmacology and therapeutic significance of a new lipid-lowering agent. Am. Heart J. 143, 356-365. http://dx.doi.org/10.1067/mhj.2002.119997 PMid:11835043

Greyling A, DeWitt C, Oosthuizen W, Jerling J. 2006. Effects of a policosanol supplement on serum lipid concentrations in hypercholesterolemic and heterozygous familial hypercholesterolemic subjects. Br. J. Nutr. 95, 968–975. http://dx.doi.org/10.1079/BJN20061715 PMid:16611388

Haim D, Berrios M, Valenzuela A, Videla L. 2009. Trace quantification of 1-octacosanol and 1-triacontanol and their main metabolites in plasma by liquid-liquid extraction coupled with gas chromatography mass spectrometry. J. Chromatogr. B. Biomed. Appl. 887, 4154-4158.

Haim D, Videla L. 2008. Policosanols, protective natural compounds in cardiovascular disease. Agro Food Industry Hi-Tech. 19, 60-63.

Hargrove JL, Greenspan P, Hartle DK. 2004. Nutritional significance and metabolism of very long chain fatty alcohols and acids from dietary waxes. Exp. Biol. Med. 229, 215-226.

Hayes KC, Khosla P. 1992. Dietary fatty acid thresholds and cholesterolemia. FASEB J6, 2600-2607. PMid:1592210

Hernandez F, Illnait J, Mas R. 1992. Effect of policosanol on serum lipid and lipoproteins in healthy volunteers. Curr. Ther. Res. Clin. Exp. 51, 568-575.

Janikula M. 2002. Policosanol: a new treatment for cardiovascular disease? Altern. Med. Rev. 7, 203-217. PMid:12126462

Kabir Y, Kimura S. 1993. Biodistribution and metabolism of orally administered octacosanol in rats. Ann. Nutr. Metab. 37, 33-38. http://dx.doi.org/10.1159/000177746 PMid:8470870

Kassis AN, Jones PJ. 2006. Lack of cholesterol-lowering efficacy of Cuban sugar cane policosanols in hypercholesterolemic persons. Am. J. Clin. Nutr. 84, 1003-1008. PMid:17093150

Kassis AN, Marinangeli CP, Jain D, Ebine N, Jones PJ. 2007. Lack of effect of sugar cane policosanol on plasma cholesterol in Golden Syrian hamsters. Atherosclerosis 194, 153-158. http://dx.doi.org/10.1016/j.atherosclerosis.2006.10.008 PMid:17123537

Keller S, Gimmler F. 2008. Octacosanol administration to humans decreases neutral sterol and bile acid concentration in feces. Lipids. 43, 109-115. http://dx.doi.org/10.1007/s11745-007-3127-4 PMid:18004604

Laemmli UK. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227, 680-685. http://dx.doi.org/10.1038/227680a0 PMid:5432063

Marrero D, González-Bravo L. 2001. Trace determination of 1-octacosanol in rat plasma by solid-phase extraction with Tenax GC and capillary gas chromatography. J. Chromatogr B. Biomed. Appl. 762, 43-49. http://dx.doi.org/10.1016/S0378-4347(01)00331-0

Mas R, Castaño G, Illnait J, Fernandez L, Fernandez J, Aleman C, Pontigas V, Lescay M. 1999. Effects of policosanol in patients with type II hypercholesterolemia and additional coronary risk factors. Clin. Pharmacol. Ther. 65, 439-447. http://dx.doi.org/10.1016/S0009-9236(99)70139-6

Mendoza S, Gamez R, Noa M, Mas R, Castaño G, Mesa R, Mesa MS, Armas M. 2001. Comparison of the effects of D-003 and policosanol on lipid profile and endothelial cells in normocholesterolemic rabbits. Curr. Ther. Res. 62, 209-220. http://dx.doi.org/10.1016/S0011-393X(01)80032-1

Menendez R, Amor AM, Gonzalez RM, Fraga V, Mas R. 1996. Effect of policosanol on the hepatic cholesterol biosynthesis of normocholesterolemic rats. Biol. Res. 29, 253-257. PMid:9278716

Menéndez R, Amor AM, Rodeiro I, González RM, Gonzalez PC, Alfonso JL, Mas R. 2001. Policosanol modulates HMG-CoA reductase activity in cultured fibroblasts. Arch. Med. Res. 31, 8-12. http://dx.doi.org/10.1016/S0188-4409(00)00265-4

Menéndez R, Marrero D, Más R, Fernández I, González L, González RM. 2005. In vitro and in vivo study of octacosanol metabolism. Arch. Med. Res. 36, 113–119. http://dx.doi.org/10.1016/j.arcmed.2004.12.006 PMid:15847942

Murphy KJ, Saint DA, Howe PR. 2008. Lack of effect of sugar cane and sunflower seed policosanols on plasma cholesterol in rabbits. J. Am. Coll. Nutr. 27, 476-484. PMid:18978167

Ng TK, Hayes KC, DeWitt GF, Jegathesan M, Satgunasingam N, Ong AS, Tan D. 1992. Dietary palmitic acid and oleic acid exert similar effects on serum cholesterol and lipoprotein profiles in normocholesterolemic men and women. J. Am. Coll. Nutr. 11, 383-390. PMid:1506599

Ng Chi H, Leung Ka Y, Huan Y, Cehn Zhen Y. 2005. Policosanol has no antioxidant activity in human lowdensity lipoprotein but increases excretion of bile acids in hamsters. J. Agric. Food Chem. 53, 6289-6293. http://dx.doi.org/10.1021/jf051269a PMid:16076108

Nissinen MJ, Gylling H, Miettinen TA. 2006. Effects of plant stanol esters supplied in a fat free milieu by pastilles on cholesterol metabolism in colectomized human subjects. Nutr. Metab. Cardiovasc. Dis. 16, 426-435. http://dx.doi.org/10.1016/j.numecd.2005.07.005 PMid:16935701

Oliaro-Bosso S, Calcio Gaudino E, Mantegna S, Giraudo E, Meda C, Viola F, Cravotto G. 2009. Regulation of HMG-CoA reductase activity by policosanol and octacosadienol, a new synthetic analogue of octacosanol. Lipids. 44, 907-916. http://dx.doi.org/10.1007/s11745-009-3338-y PMid:19763655

Place AR. 1992. Comparative aspects of lipid digestion and absorption: physiological correlates of wax ester digestion. Am. J. Physiol. 263, R464–R471. PMid:1415629

Pons P, Mas R, Illnait J, Fernandez L, Rodriguez M, Robaina C, Fernández JC. 1992. Efficacy and safety of policosanol in patients with primary hypercholesterolemia. Curr. Ther. Res. Clin. Exp. 52, 507-513. http://dx.doi.org/10.1016/S0011-393X(05)80456-4

Prat H, Roman O, Pino E. 1999. Comparative effects of policosanol and two HMG-CoA reductase inhibitors on type II hypercholesterolemia. Rev. Med. Chile 127, 286-294. PMid:10436712

Sánchez-Muniz FJ, Cruz-Merinero M, Rodríguez-Gil S, Ordovás JM, Ródenas S, Cuesta C. 2002. Dietary fat saturation affects apolipoprotein AII levels and HDL composition in postmenopausal women. J. Nutr. 132, 50-54. PMid:11773507

Singh BK, Mehta JL. 2002. Management of dyslipidemia in the primary prevention of coronary heart disease. Curr. Opin. Cardiol. 17, 503-511. http://dx.doi.org/10.1097/00001573-200209000-00010 PMid:12357127

Singh D, Li L, Porter T. 2006. Policosanol inhibits cholesterol synthesis in hepatoma cells by activation of AMP kinase. J. Pharm. Exp. Therap. 318, 1020-1026. http://dx.doi.org/10.1124/jpet.106.107144 PMid:16714400

Torres O, Agramonte AJ, Más R, Fernández L, Fernández JC. 1995. Treatment of hypercholesterolemia in NIDDM with policosanol. Diabetes Care. 18, 393–397. http://dx.doi.org/10.2337/diacare.18.3.393 PMid:7555484

Towbin H, Staehelin T, Gordon J. 1979. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl. Acad. Sci. USA. 76, 4350-4354. http://dx.doi.org/10.1073/pnas.76.9.4350 PMid:388439 PMCid:411572

Wong AK, Howie J, Petrie JR, Lang CC. 2009. AMPactivated protein kinase pathway: a potential therapeutic target in cardiometabolic disease. Clin. Sci. 16, 607-620. http://dx.doi.org/10.1042/CS20080066 PMid:19275766 PMCid:2762688

Wu T, Fu J, Yang Y, Zhang L, Han J. 2009. The effects of phytosterols/stanols on blood lipid profiles: a systematic review with meta-analysis. Asia Pac. J. Clin. Nutr. 18, 179-186. PMid:19713176

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Publicado

2012-12-30

Cómo citar

1.
Haim D, Valenzuela A, Brañes MC, Fuenzalida M, Videla LA. La esterificación de ácido oleico en policosanoles aumenta su biodisponibilidad y el efecto hipocolesterolémico en ratas. Grasas aceites [Internet]. 30 de diciembre de 2012 [citado 7 de agosto de 2026];63(4):345-54. Disponible en: https://grasasyaceites.revistas.csic.es/index.php/grasasyaceites/article/view/1388

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Investigación