Bổ Sung Selenium Làm Giảm Xơ Hoá Gan Ở Chuột Sau Khi Tiêm Carbon Tetraclorua Mạn Tính

Biological Trace Element Research - Tập 133 - Trang 83-97 - 2009
Ming Ding1, James J. Potter1, Xiaopu Liu1, Michael S. Torbenson2, Esteban Mezey1,3
1Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, USA
2Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, USA
3The Johns Hopkins University School of Medicine, Baltimore, USA

Tóm tắt

Căng thẳng ôxy kích thích sự hình thành xơ, và selenium (Se) có các đặc tính chống ôxy hóa. Nghiên cứu này nhằm xác định xem việc bổ sung Se có ảnh hưởng đến tổn thương gan và xơ hóa do nguồn cung cấp CCl4 hay không. Chuột được tiêm CCl4 trong 4 tuần, trong khi nhóm đối chứng nhận dầu ô liu. Se được cung cấp dưới dạng natri selenit trong nước uống. Se đã làm tăng hoạt tính glutathione peroxidase phụ thuộc vào Se trong gan và giảm malondialdehyde trong gan sau khi tiêm CCl4. Se làm giảm viêm gan nhưng không làm giảm hoại tử do CCl4 gây ra. Se tăng apoptosis của tế bào gan sau khi tiêm CCl4 và các protein BAX và Bcl Xs/l pro-apoptotic. Apoptosis của tế bào hình sao xảy ra chỉ sau khi tiêm CCl4 ở chuột được bổ sung Se. Se làm giảm số lượng tế bào hình sao và xơ hóa sau khi tiêm CCl4. Matrix metalloproteinase-9 trong gan tăng lên sau khi tiêm CCl4 với bổ sung Se. Tóm lại, bổ sung Se đã làm giảm xơ hoá gan sau CCl4 trong bối cảnh viêm giảm nhưng apoptosis tăng. Các cơ chế chính cho sự giảm xơ hóa là số lượng tế bào hình sao sản xuất collagen thấp hơn và sự phân hủy collagen gia tăng.

Từ khóa

#Selenium #xơ hóa gan #tổn thương gan #Carbon Tetraclorua #apoptosis #tế bào hình sao

Tài liệu tham khảo

Nieto N, Friedman SL, Greenwel P, Cederbaum AI (1999) CYP2E1-mediated oxidative stress induces collagen type I expression in rat hepatic stellate cells. Hepatology 30:987–996 Chojkier M, Houglum K, Solis-Herruzo J, Brenner DA (1989) Stimulation of collagen gene expression by ascorbic acid in cultured human fibroblasts. A role for lipid peroxidation? J Biol Chem 264:16957–16962 Maher JJ, Tzagarakis C, Gimenez A (1994) Malondialdehyde stimulates collagen production by hepatic lipocytes only upon activation in primary culture. Alcohol Alcohol 29:605–610 Novitskiy G, Potter JJ, Wang L, Mezey E (2006) Influences of reactive oxygen species and nitric oxide on hepatic fibrogenesis. Liver Int 26:1248–1257 Aram G, Potter JJ, Liu X, Torbenson MS, Mezey E (2009) Deficiency of NAD(P) H oxidase enhances hepatocellular injury but attenuates fibrosis after chronic carbon tetrachloride administration. Hepatology 49:911–919 Bedwal RS, Nair N, Sharma MP, Mathur RS (1993) Selenium—its biological perspectives. Med Hypotheses 41:150–159 Luoma PV, Sotaniemi EA, Korpela H, Kumpulainen J (1984) Serum selenium, glutathione peroxidase activity and high density lipoprotein cholesterol—effect of selenium supplementation. Res Commun Chem Pathol Pharmacol 46:469–472 Valimaki M, Alfthan G, Pikkarainen J, Ylikahri R, Salaspuro M (1987) Blood and liver selenium concentrations in patients with liver diseases. Clin Chim Acta 166:171–176 Thuluvath PJ, Triger DR (1992) Selenium in chronic liver disease. J Hepatol 14:176–182 Wenzel G, Kuklinski B, Ruhlmann C, Ehrhardt D (1993) Alkoholtoxische hepatitis—‘eine frei Radikale’ assoziierte Erkrankung. Letalitatssenkung durch adjuvante Antioxidantientherapie. Inn Med 48:490–496 Stewart S, Prince M, Bassendine M, Hudson M, James O, Jones D, Record C, Day CP (2007) A randomized trial of antioxidant therapy alone or with corticosteroids in acute alcoholic hepatitis. J Hepatol 47:277–283 Chen L, Pan DD, Zhou J, Jiang YZ (2005) Protective effect of selenium enriched lactobacillus on CCl4-induced liver injury in mice and its possible mechanisms. World J Gastroenterol 11:5795–5800 Shen XH, Cheng WF, Li XH, Sun JQ, Li F, Ma L, Xie LM (2005) Effects of dietary supplementation with vitamin E and selenium on rat hepatic stellate cell apoptosis. World J Gastroenterol 11:4957–4961 Horwitz W, Latimer Jr. GW (eds) (2005) Official methods of analysis of AOAC international, 18th edn, Chapter 4. Gaithersburg, MD. p. 62–64 Potter JJ, Rennie-Tankersley L, Mezey E (2003) Influence of leptin in the development of hepatic fibrosis produced in mice by Schistosoma mansoni infection and by chronic carbon tetrachloride administration. J Hepatol 38:281–288 Bergmeyer HU, Scheibe P, Wahlefeld AW (1978) Optimization of methods for aspartate aminotransferase and alanine aminotransferase. Clin Chem 24:58–73 Uchiyama M, Mihara M (1978) Determination of malondialdehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86:271–278 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275 Hernandez-Munoz R, Diaz-Munoz M, Suarez-Cuenca JA, Trejo-Solis C, Lopez V, Sanchez-Sevilla L, Yanez L, Chagoya de Sanchez V (2001) Adenosine reverses a preestablished CCl4-induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in rats. Hepatology 34:677–687 Zhou X, Hovell CJ, Pawley S, Hutchings MI, Arthur MJP, Iredale JP, Benyon RC (2004) Expression of matrix metalloproteinase-2 and -14 persists during early resolution of experimental liver fibrosis and might contribute to fibrolysis. Liver Int 24:492–501 Mezey E, Potter JJ, Slusser RJ, Abdi W (1977) Changes in hepatic collagen metabolism in rats produced by chronic ethanol feeding. Lab Invest 36:206–214 Benyon RC, Arthur MJP (2001) Extracellular matrix degradation and the role of hepatic stellate cells. Semin Liver Dis 21:373–384 Zeng H, Briske-Anderson M, Idso JP, Hunt CD (2006) The selenium metabolite methylselenol inhibits the migration and invasion potential of HT1080 tumor cells. J Nutr 136:1528–1532 Kim SH, Johnson VJ, Shin TY, Sharma RP (2004) Selenium attenuates lipopolysaccharide-induced oxidative stress responses through modulation of p38 MAPK and NF-κB signaling pathways. Exp Biol Med 229:203–213 Vunta H, Belda BJ, Arner RJ, Reddy CC, Vanden Heuvel JP, Prabhu KS (2008) Selenium attenuates pro-inflammatory gene expression in macrophages. Mol Nutr Food Res 52:1316–1323 Nolan JP, Leibowitz AI (1978) Endotoxin and the liver. III. Modification of acute carbon tetrachloride injury by polymixin B—an antiendotoxin. Gastroenterology 75:445–449 Shen HM, Yang CF, Ong CN (1999) Sodium selenite-induced oxidative stress and apoptosis in human hepatoma HepG2 cells. Int J Cancer 81:820–828 Rikiishi H (2007) Apoptotic cellular events for selenium compounds involved in cancer prevention. J Bioenerg Biomembr 39:91–98 Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, Howell C, Arthur MJP (1998) Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest 102:538–549 Galle PR, Hofmann WJ, Walczak H, Schaller H, Otto G, Stremmel W, Krammer PH, Runkel L (1995) Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. J Exp Med 182:1223–1230 Wilson AC, Thompson HJ, Schedin PJ, Gibson NW, Ganther HE (1992) Effect of methylated forms of selenium on cell viability and the induction of DNA strand breakage. Biochem Pharmacol 43:1137–1141 Jiang C, Wang Z, Ganther H, Lu J (2001) Caspases as key executors of methyl selenium-induced apoptosis (Anoikis) of DU-145 prostate cancer cells. Cancer Res 61:3062–3070 Berk RF, Lane JM, Patel K (1984) Relationship of oxygen and glutathione in protection against carbon tetrachloride-induced hepatic microsomal lipid peroxidation and covalent binding in the rat. Rationale for the use of hyperbaric oxygen to treat carbon tetrachloride ingestion. J Clin Invest 74:1996–2001 Wardman P (1988) Conjugation and oxidation of glutathione via thiyl free radicals. In: Sies H, Ketterer B (eds) Glutathione conjugation. Mechanisms and biological significance. Academic, London, pp 43–72 Siwik DA, Pagano PJ, Colucci WS (2001) Oxidative stress regulates collagen synthesis and matrix metalloproteinase activity in cardiac fibroblasts. Am J Physiol Cell Physiol 280:C53–C60 Leon H, Bautista-Lopez N, Sawicka J, Schultz R (2007) Hydrogen peroxide causes cardiac dysfunction independent from its effect on matrix metalloproteinase-2 activation. Can J Physiol Pharmacol 85:341–348