Formación de cálculos biliares de colesterol. Nuevos avances científicos
Resumen
La investigación científica sobre la formación de cálculos biliares de colesterol, ha comprobado la participación de numerosos genes, entre los cuales se encuentran receptores nucleares y transportadores biliares. El desequilibrio fisicoquímico entre los lípidos biliares más importantes produce hipersecreción de colesterol en la bilis, una etapa necesaria para sobresaturar la vesícula biliar. Las sales biliares son insuficientes para solubilizar al colesterol en micelas mixtas, por lo que esta molécula se solubiliza, en su mayoría, dentro de liposomas (fosfolípidos y escasas sales biliares), y en ellos existe en alta concentración, que tiende a precipitar y a formar cristales, evento considerado como limitante para la formación de cálculos biliares. El desarrollo del cálculo puede acelerarse si existe hipersecreción de proteínas mucinas y escasa motilidad vesicular. La presente revisión tiene el objetivo de informar los nuevos aportes científicos sobre la formación de cálculos biliares de colesterol, analizando y discutiendo sus resultados enfocados a la búsqueda de tratamientos farmacológicos, porque la litiasis no tiene terapia eficaz y la colecistectomía es el método quirúrgico invasivo, cuando la enfermedad produce síntomas.
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Casper M, Lammert F. Gallstone disease: basic mechanism, diagnosis and therapy. Praxis 2011;100(23):1403-1412.
Ruhl CE, Everhart JE. Gallstone disease is associated with increased mortality in the United States. Gastroenterology 2011; 140(2):508-516.
Portincasa P, Di Ciaula A, Wang HH, Moschetta A, Wang DQ. Medicinal treatments of cholesterol gallstones: old, current and new perspectives. Curr Med Chem 2009;16(12):1531-1542.
Jarrar BM, Al-Rowaii MA. Chemical composition of gallstones from Al-jouf province of saudi Arabia. Malays J Med Sci 2011; 18(2):47-52.
Van Erpecum KJ. Pathogenesis of cholesterol and pigment gallstones: an update. Clin Res Hepatol Gastroenterol 2011;35(4): 281-287.
Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstones disease. Lancet 2006;368(9531):230-239. [ Links ]
Reddy RRL, Srinivasan K. Effect dietary fenugreek seeds on biliary proteins that influence nucleation of cholesterol crystals in bile. Steroids 2011;76(5):455-463.
Koppisetti S, Jenigiri B, Terron MP, et al. Reactive oxygen species and the hypomotility of the gallbladder as target for the treatment of gallstones with melatonin: a review. Dig Dis Sci 2008;53(10): 2592-2603.
Hofmann AF. Biliary secretion and excretion in health and disease: current concepts. Ann Hepatol 2007;6(1):15-27.
Gadaleta RM, van Mil SW, Oldenburg B, Sierseman PD, Klomp LW, van Erpecum KJ. Bile acids and their nuclear receptor FXR: relevance for hepatobiliary and gastrointestinal disease. Biochim Biophys Acta 2010;1801(7):683-692.
Stokes CS, Lammert F. Transporters in cholelithiasis. Biol Chem 2011. PMID: 22059852.
Nicolau M, Andress EJ, Zolnerciks JK, Dixon PH, Williamson C, Linton KJ. Canalicular ABC transporters and liver disease. J Pathol 2012;226(2):300-315.
Oude Elferink RP, Beuers U. Targeting the ABCB4 gene to control cholesterol homeostasis. Expert Opin Ther Targets 2011; 15(10):1173-1182.
Kuo KK, Shin SJ, Chen ZC, Yang YH, Yang JF, Hsiao PJ. Significant association of ABCG5 604Q and ABCG8 D19H polymorphisms with gallstone disease. Br J Surg 2008;95(8):1005-1011.
Dikkers A, Tietge UJ. Biliary cholesterol secretion: more than a simple ABC. World J Gastroenterol 2010;16(47):5936-5945.
Acalovschi M, Tirziu S, Chiorean E, Krawczyk M, Grünhage F, Lammert F. Common variants of ABCB4 and ABCB11 and plasma lipid levels: a study in sib pairs with gallstones, and controls. Lipids 2009;44(6):521-526.
Wang HH, Lammert F, Schmitz A, Wang DQ. Transgenic overexpression of ABCB11 enhances biliary bile salt outputs, but does not affect cholesterol cholelithogenesis in mice. Eur J Clin Invest 2010;40(6):541-551.
Katsika D, Magnusson P, Krawczyk M, Grünhage F, Lichtenstein P, Einarsson C, et al. Gallstone disease in Swedish twins: risk is associated with ABCG8 D19H genotype. J Intern Med 2010; 268(3):279-285.
Pramfalk C, Jiang ZY, Parini P. Hepatic Niemann-Pick C1-like 1. Curr Opin Lipidol 2011;22(3):225-230.
de Bario O, Neuschwander-Tetri BA, Liu M, Portincasa P, Wang DQ. Ezetimibe: its novel effects on the prevention and the treatment of cholesterol gallstones and nonalcoholic Fatty liver disease. J Lipids 2012; PMID: 2213-2342.
Wang HH, Portincasa P, Méndez-Sánchez N, Uribe M, Wang DQ. Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones. Gastroenterology 2008;134(7):2101-2110.
Zúñiga S, Molina H, Azocar L, Amigo L, Nervi F, Pimentel F, et al. Ezetimibe prevents cholesterol gallstone formation in mice. Liver Int 2008;28(7):906-907.
Dikkers A, Tietge UJ. Biliary cholesterol secretion: more than a simple ABC. World J Gastroenterol. 2010;16(47):5936-5945.
Storey SM, Mclntosh AL, Huang H, Landrock KK, Martin GG, Landrock D, et al. Intracellular cholesterol binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes. Am J Physiol Gastrointest Liver Physiol 2012; PMID: 22241858.
Pramfalk C, Jiang ZY, Cai Q, Hu H, Zhang SD, Han TQ, et al. HNF1a and SREBP2 are important regulators of NPC1L1 in human liver. J Lipid Res 2010;51:1354-1362.
Rodríguez-Cantú LN, Gutiérrez-Uribe JA, Arriola-Vucovich J, Díaz-De La Garza RI, Fahey JW, Serna-Saldívar SO. Broccoli (Brasica oleracea var. italica) sprouts and extracts in glucosinolates and isothiocyanates affect cholesterol metabolism and genes involved in lipid homeostasis in hamsters. J Agric Food Chem 2011;59(4):1095-1103.
Wang DQ, Cohen DE, Carey MC. Biliary lipids and cholesterol gallstone disease. J Lipid Res 2009;50 Suppl: S406-411.
Liu CL, Chang SJ, Chiang HJ. Quantitative analysis of cholesterol nucleation with time in supersaturated model bile. Chem Phys Lipids 2011;164(2):125-130.
Reddy RRL, Srinivasan K. Effect dietary fenugreek seeds on biliary proteins that influence nucleation of cholesterol crystals in bile. Steroids 2011;76(5):455-463.
Chuang SC, His E, Wang SN, Yu ML, Lee KT, Juo SH. Polymorphism at the mucin-like protoadherin gene influences susceptibility to gallstone disease. Clin Chim Acta 2011;412(23-24): 2089-2093.
Yang L, Chen JH, Cai D, Wang LY, Zha XL. Osteopontin and integrin are involved in cholesterol gallstone formation. Med Sci Monit 2012;18(1):16-23.
Yang L, Chen JH, Cai D, Wang LY, Zha XL. Osteopontin plays an anti-nucleation role in cholesterol gallstone formation. Hepatol Res 2011;41(5):437-445.
Andrianifahanana M, Moniaux N, Batra SK. Regulation of mucin expression: mechanistic aspects and implications for cancer and inflammatory diseases. Biochim Biophys Acta 2006; 1765(2):189-222.
Zen Y, Harada K, Sasaki M, Tsuneyama K, Katayanagi K, Yamamoto Y, et al. Lipopolysaccharide induces overexpression of MUC2 and MUC5AC in cultured biliary epithelial cells: possible key phenomenon of hepatolithiasis. Am J Pathol 2002;161(4): 1475-1484.
Maurer KJ, Carey MC, Fox JG. Roles of infection, inflammation and immune system in cholesterol gallstone formation. Gastroenterology 2009;136(2):425-440.
Koppisetti S, Jenigiri B, Terron MP, Tengatiini S, Tamura H, Flores LJ, et al. Reactive oxygen species and the hypomotility of the gall bladder as targets for the treatment of gallstones with melatonin: a review. Dig Dis Sci 2008;53(10):2592-2603.
Nihei N, Sekime A, Miyasaka K, Kanai S, Takiguchi S, Funakoshi A. Administration of ursodeoxycholate failed to prevent sludge and/or gallstone formation in cholecystokinin-1(A) receptor-deficient mice. Biomed Res 2011;32(6):401-406.
Lo Sasso G, Petruzzelli M, Moschetta A. A translational view on the biliary lipid secretory network. Biochim Biophys Acta 2008;1781(3):79-96.
Modica S, Gadaleta RM, Moschetta A. Deciphering the nuclear bile acid receptor FXR paradigm. Nucl Recept Signal 2010; 8:e005.
Gadaleta RM, van Mill SW, Oldenburg B, Siersema PD, Klomp LW, van Erpecum KJ. Bile acids and their nuclear receptor FXR: Relevance for hepatobiliary and gastrointestinal disease. Biochim Biophys Acta 2010;1801(7):683-692.
Bergheim I, Harsch S, Mueller O, Schimmel S, Fritz P, Stange EF. Apical sodium bile acid transporter and ileal lipid binding protein in gallstone carriers. J Lipid Res 2006;47(1):42-50.
Renner O, Harsch S, Strohmeyer A, Schimmel S, Stange EF. Reduced ileal expression of OST alpha-OST beta in non-obese gallstone disease. J Lipid Res 2008;49(9):2045-2054.
Kovacs P, Kress R, Rocha J, Kurtz U, Miquel JF, Nervi F, et al. Variation of the gene encoding the nuclear bile salt receptor FXR and gallstone susceptibility in mice and humans. J Hepatol 2008; 48(1):116-124.
Vázquez MC, Rigotti A, Zanlungo S. Molecular mechanism underlying the link between nuclear receptors function and cholesterol gallstone formation. J Lipids 2012; PMID:22132343.
Uppal H, Zhai Y, Gangopadhyay A, Khadem S, Ren S, Moser JA, et al. Activation of liver X receptor sensitizes mice to gallbladder cholesterol crystallization. Hepatology 2008;47(4): 1331-1342.
Hou L, Shu XO, Gao YT, Ji BT, Weiss JM, Yang G, et al. Anthropometric measurements, physical activity and the risk of symptomatic gallstone disease in Chinese women. Ann Epidemiol 2009;19(5):344-350.
He J, Nishida S, Xu M, Makishima M, Xie W. PXR prevents cholesterol gallstone disease by regulating biosynthesis and transport of bile salts. Gastroenterology 2011;140(7):2095-2106.
DOI: http://dx.doi.org/10.61155/gen.v66i1.187
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