Tác động của Amlodipine, Captopril và Bezafibrate lên môi trường oxy hóa ở chuột có gan nhiễm mỡ

Digestive Diseases and Sciences - Tập 53 - Trang 777-784 - 2007
Zvi Ackerman1,2, Mor Oron-Herman3,4, Talma Rosenthal3, Orit Pappo2,5, Gabriela Link2,6, Ben-Ami Sela3,4, Maria Grozovski7
1Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
2Hebrew University Medical School, Jerusalem, Israel
3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
4Institute of Chemical Pathology, Sheba Medical Center, Tel Hashomer, Israel
5Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
6Department of Human Nutrition and Metabolism, Hebrew University Medical School, Jerusalem, Israel
7Ort Braude College of Engineering, Karmiel, Israel

Tóm tắt

Căng thẳng oxy hóa có thể khởi phát tổn thương tế bào gan đáng kể ở những người có gan nhiễm mỡ. Chúng tôi đã đặc trưng hóa những thay đổi trong các tham số chống oxy hóa gan ở chuột được cho ăn chế độ ăn giàu fructose (FED) có và không có thuốc để giảm huyết áp hoặc triglycerides huyết tương. Chuột FED có sự gia tăng nồng độ malondialdehyde (MDA), giảm nồng độ α-tocopherol, giảm hoạt động paraoxonase (PON), gia tăng hoạt động glutathione peroxidase (GSH-Px) và glutathione reductase (GSSG-R). Amlodipine làm tăng PON và GSH-Px, nhưng làm giảm hoạt động GSSG-R và nồng độ α-tocopherol. Captopril làm giảm nồng độ MDA và hoạt động của cả GSH-Px và GSSG-R, nhưng làm tăng nồng độ α-tocopherol và hoạt động PON. Bezafibrate làm tăng nồng độ α-tocopherol và hoạt động PON, nhưng làm giảm hoạt động của GSSG-R. Các động vật có gan nhiễm mỡ cho thấy sự gia tăng căng thẳng peroxidative nhưng cũng có sự thiếu hụt trong các con đường chống oxy hóa. Các loại thuốc được sử dụng để điều trị huyết áp cao và tăng triglyceride có thể dẫn đến nhiều thay đổi khác nhau trong môi trường oxy hóa và chống oxy hóa của gan.

Từ khóa

#stress oxy hóa #gan nhiễm mỡ #amlodipine #captopril #bezafibrate

Tài liệu tham khảo

Sanyal AJ (2002) AGA technical review on non-alcoholic fatty liver disease. Gastroenterology 123:1705–1725 Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N, Rizzetto M (2003) Non-alcoholic fatty liver, steatohepatis and the metabolic syndrome. Hepatology 37:917–923 Chitturi S, Abeygunasekera S, Farrell GC, Holmes-Walker J, Hui JM, Fung C, Karim R, Lin R, Samarasinghe D, Liddle C, Weltman M, George J (2002) NASH and insulin resistance, insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology 35:373–379 Musso G, Gambino R, De Michieli F, Cassader M, Rizzetto M, Durazzo F, Faga F, Silli B, Pagano G (2003) Dietary habits and their relations to insulin resistance and postprandial lipemia in non-alcoholic steatohepatitis. Hepatology 37:909–916 Angulo P, Keach JC, Batts KP, Lindor KD (1999) Independent predictors of liver fibrosis in patients with non-alcoholic steatohepatitis. Hepatology 30:1356–1362 Day CP, James OF (1998) Steatohepatitis: a tale of two “hits”? Gastroenterology 114:842–845 Loguercio C, De Girolamo J, de Sio I, Tuccillo C, Ascione A, Baldi F, Budillon G, Cimino L, Di Carlo A, Di Marino MP, Mrisco F, Picciotto F, Terrracciano L, Vecchione R, Verde V, Del Vecchio Blanco C (2000) Non-alcoholic liver disease in an area of Southern Italy: main clinical, histological and pathophysiological aspects. J Hepatol 35:568–574 MacDonald GA, Bridle KR, Ward PJ, Walker NI, Houglum K, George DK, Smith JL, Powell LW, Graford DH, Ramm GA (2001) Lipid peroxidation in hepatic steatosis in humans is associated with hepatic fibrosis and occurs predominantly in acinar zone 3. J Gastroenterol Hepatol 16:599–606 Seki S, Kitada T, Yamada T, Sakaguchi H, Nakatani K, Wakasa K (2002) In situ detection of lipid peroxdation and oxidative DNA damage in non-alcoholic fatty liver disease. J Hepatol 37:56–62 Koruk M, Taysi S, Savas MC, Yilmaz O, Akcay F, Karakok M (2004) Oxidative stress and enzymatic antioxidant status in patients with non-alcoholic steatohepatitis. Ann Clin Lab Sci 34:57–62 Videla LA, Rodrigo R, Orellana M, Fernandez V, Tapia G, Qinones L, Varela N, Contreras J, Lazarte R, Csendes A, Rojas J, Maluenda F, Burdiles P, Diaz JC, Smok G, Thielemann L, Poniachik J (2004) Oxidative stress-related parameters in liver of non-alcoholic fatty liver disease patients. Clin Sci 106:261–268 Chalasani N, Deeg MA, Crabb DW (2004) Systemic levels of lipid peroxidation and its metabolic and dietary correlates in patients with non-alcoholic steatohepatitis. Am J Gastroenterol 99:1497–1502 Malaguarnera L, Madeddu R, Palio E, Arena N, Malaguarnera M (2005) Heme-oxygenase-1 levels and oxidative stress-related parameters in non-alcoholic fatty liver disease patients. J Hepatol 42:585–591 Bahcecioglu IH, Yalniz M, Ilhan N, Ataseven H, Ozercan IH (2005) Levels of serum vitamin A, alpha-tocopherol and malondialdehyde in patients with non-alcoholic steatohepatitis: relationship with histopathologic severity. Int J Clin Pract 59:318–323 George J, Pera N, Phung N, Leclercq I,Yun Hou J, Farrell G (2003) Lipid peroxidation, stellate cell activation and hepatic fibrogenesis in a rat model of chronic steatohepatitis. J Hepatol 39:756–764 Weltman MD, Farrell GC, Liddle C (1996) Increased CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation. Gastroenterology 111:1645–1653 Sreekumar R, Rosado B, Rasmussen D, Charlton M (2003) Hepatic gene expression in histologically progressive non-alcoholic steatohepatitis. Hepatology 38:244–251 Fromenty B, Robin MA, Igoudjil A, Mansouri A, Pessayre D (2004) The ins and outs of mitochondrial dysfunction in NASH. Diabetes Metab 30:121–138 Ibdah JA, Perlegas P, Zhao Y, Angdisen J, Borgerink H, Shadoan MK, Wagner JD, Matern D, Rinaldo P, Cline JM (2005) Mice heterozygous for a defect in mitochondrial trifunctional protein develop hepatic steatosis and insulin resistance. Gastroenterology 128:1381–1390 Oron-Herman M, Sela BA, Rosenthal T (2005) Risk reduction therapy for syndrome X: comparison of several treatments. Am J Hypert 18:372–378 Ackerman Z, Oron-Herman M, Grozovski M, Rosenthal T, Pappo O, Link G, Sela BA (2005) Fructose induced fatty liver. Hepatic effects of blood pressure and plasma triglyceride reduction. Hypertension 45:1012–1018 Friedman SL (2004) Stellate cells: a moving target in hepatic fibrogenesis. Hepatology 40:1041–1043 Yagi K (1987) Lipid peroxides and human diseases. Chem Phys Lipids 45:337–351 Folch J, Lees M, Sloane Stanley GH (1957) A simple method for isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509 Baker H, Frank O, DeAngelis B, Feingold S (1980) Plasma tocopherol in man at various times after ingesting free and acetylated tocopherol. Nutr Rpts Int 21:531–536 Gan KN, Smolen A, Eckerson HW, La Du BN (1991) Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos 19:100–106 Beutler E (1975) Glutathione peroxidase. In: Beutler E (ed) Red cell metabolsim: a manual of biochemical methods, 2nd edn. Grune and Strottan, New York, pp 71–73 Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490 Bradford MM (1976) A rapid and sensitive method for quantitation of micrograme quantities of protein utilizing the principle of protein dye-binding. Anal Biochem 72:248–254 Lettéron P, Fromenty B, Terris B, Degott C, Pessayre D (1996) Acute and chronic steatosis lead to in vivo lipid peroxidation in mice. J Hepatol 24:200–208 Parola M, Pinzani M, Casini A, Albano E, Poli G, Gentilini A, Gentilini P, Dianzani MU (1993) Stimulation of lipid peroxidation or 4-hydroxynonenal treatment increases procollagen α 1(I) gene expression in human liver fat-storing cells. Biochem Biophys Res Commun 194:1044–1050 Nieto N, Friedman SL, Cederbaum AI (2002) Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P450 2E1 derived reactive oxygen species. Hepatology 35:62–73 Browning JD, Horton JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114:147–152 Albano E, Mottaran E, Vidali M, Reale E, Saksena S, Occhino G, Burt AD, Day CP (2005) Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis. Gut 54:987–993 Strauss RS (1999) Comparison of serum concentration of α-tocopherol and β-carotene in a cross-sectional sample of obese and non-obese children (NHANES III). J Pediatr 134:160–165 Ferré N, Camps J, Prats E, Girona J, Gomez F, Heras M, Simo JM, Ribalta J, Joven J (2002) Impaired vitamin E status in patients with parenchymal liver cirrhosis: relationships with lipoprotein compositional alterations, nutritional factors and oxidative susceptibility of plasma. Metabolism 51:609–615 Chojkier M, Houglum K, Lee KS, Buck M (1998) Long- and short-term D-α-tocopherol supplementation inhibits liver collagen α 1(I) gene expression. Am J Physiol Gastrointest Liver Physiol 275:G1480–G1485 Parola M, Muraca R, Dianzani I, Barrera G, Leonarduzzi G, Bendinelli P, Piccoletti R, Poli G (1992) Vitamin E dietary supplementation inhibits transforming growth factor beta-1 gene expression in the rat liver. FEBS Lett 308:267–270 Kawanaka M, Mahmood S, Niiyama G, Izumi A, Kamei A, Ikeda H, Suehiro M, Togawa K, Sasagawa T, Okita M, Nakamura H, Yodoi J, Yamada G (2004) Control of oxidative stress and reduction in biochemical markers by vitamin E treatment in patients with non-alcoholic steatohepatitis: a pilot study. Hepatol Res 29:39–41 Sanyal AJ, Mofrad PS, Contos MJ, Sargeant C, Luketic VA, Sterling RK, Stravitz RT, Shiffman ML, Clore J, Mills AS (2004) A pilot study of vitamin E versus vitamin B and pioglitazone for the treatment of non-alcoholic steatohepatitis. Clin Gastroenterol Hepatol 12:1107–1115 Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S (2003) Vitamin E and vitamin C treatment improves fibrosis in patients with non-alcoholic steatohepatitis. Am J Gastroenterol 98:2485–2490 Hasegawa T, Yoneda M, Nakamura K, Makino I, Terano A (2001) Plasma transforming growth factor beta-1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther 15:1667–1672 Kugelmas M, Hill DB, Vivian B, Marsano L, McClain CJ (2003) Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology 38:413–419 Adams LA, Angulo P (2003) Vitamins E and C for the treatment of NASH. Duplication of results but lack of demonstration of efficacy. Am J Gastroenterol 98:2348–2350 Costa LG, Vitalone A, Cole TB, Furlong CE (2005) Modulation of paraoxonase (PON-1) activity. Biochem Pharmacol 69:541–550 Ferré N, Camps J, Cabré M, Paul A, Joven J (2001) Hepatic paraoxonase activity alterations and free radical production in rats with experimental cirrhosis. Metabolism 9:997–1000 Ferré N, Camps J, Prats E, Vilella E, Paul A, Figuera L, Joven J (2002) Serum paraoxonase activity: a new additional test for the improved evaluation of chronic liver damage. Clin Chem 48:261–268 Shan XQ, Aw TY, Jones DP (1990) Glutathione dependent protection against oxidative injury. Pharmcol Ther 47:61–71 Nobili V, Pastore A, Gaeta LM, Tozzi G, Comparcola D, Sartorelli MR, Marcellini M, Bertini E, Piemonte F (2005) Glutathione metabolism and antioxidant enzymes in patients affected by non-alcoholic steatohepatitis. Clin Chim Acta 355:105–111 Mason RP, Mak IT, Trumbore MW, Mason PE (1999) Antioxidant properties of calcium antagonists related to membrane biophysical interactions. Am J Cardol 84(4A):16L–22L Turgan N, Habif S, Kabaroglu CG, Mutaf I, Ozmen D, Bayindir O, Uysal A (2003) Effects of the calcium channel blocker amlodipine on serum and aortic cholesterol, lipid peroxidation, antioxidant status and aortic histology in cholesterol fed rabbits. J Biomed Sci 10:65–72 Mutaf I, Habif S, Turgan N, Parildar Z, Ozmen D, Bayindir O, Uysal A (2004) Amlodipine and glutathione cycle in hypercholesterolemia. Acta Cardiol 59:485–492 de Cavanagh EM, Inserra F, Ferder L, Fraga CG (2000) Enalapril and capropril enhance glutathione-dependent antioxidant defenses in mouse tissues. Am J Physiol Regul Intergr Comp Physiol 278:R572–R577 Makowska JM, Bonner FW, Gibson GG (1990) Hepatic induction potency of hypolipidaemic drugs in the rat following long-term administration: influence of different dosing regimens. Xenobiotica 20:1121–1128 Hoffman R, Brook GJ, Aviram M (1992) Hypolipidemic drugs reduce lipoprotein susceptibility to undergo lipid peroxidation: in vitro and ex vivo studies. Atherosclerosis 93:105–113 Durrington PN, Mackness MI, Bhatnagar D, Julier K, Prais H, Arrol S, Morgan J, Wood GN (1998) Effects of two different fibric acid derivatives on lipoprotein, cholesterylester transfer, fibrinogen, plasminogen activator inhibitor and paraoxonase activity in type IIb hyperlipoproteinaemia. Atherosclerosis 138:217–225 Ohmoto K, Yoshioka N, Yamamoto S (2006) Long-term effect of bezafibrate on parameters of hepatic fibrosis in primary biliary cirrhosis. J Gastroenterol 41:502–503 Jonsson JR, Clouston AD, Ando Y, Kelemen LI, Horn MJ, Adamson MD, Purdie DM, Powell EE (2001) Angiotensin-converting enzyme inhibition attenuates the progression of hepatic fibrosis. Gastroenterology 124:148–155