Therapy of NAFLD: Antioxidants and cytoprotective agents

Journal of Clinical Gastroenterology

Volumn 40, Issue SUPPL. 1, 2006, Pages

  Chang, Charissa Y ^a   Argo, Curtis K ^a   Al Osaimi, Abdullah M S ^a   Caldwell, Stephen H ^a  

^a UNIVERSITY OF VIRGINIA HEALTH SYSTEM   (United States)

Author keywords

Antioxidants; Betaine; Cytoprotective agents; Nonalcoholic fatty liver; Nonalcoholic steatohepatitis; S adenosylmethionine; Ursodeoxycholic acid; Vitamin E

Indexed keywords

21 AMINOSTEROID; ACETYLCYSTEINE; ALANINE AMINOTRANSFERASE; ALPHA TOCOPHEROL; ANTIOXIDANT; ASCORBIC ACID; BETA CAROTENE; BETAINE; CHONDROITIN; ETHANOLAMINE; FATTY ACID; FLUOXETINE; GLUCOSAMINE; GLUCURONIC ACID; HISTAMINE; INSULIN SENSITIZING AGENT; NICOTINAMIDE; PHOSPHATIDYLCHOLINE; PIOGLITAZONE; PRAVASTATIN; PROBIOTIC AGENT; PROTECTIVE AGENT; S ADENOSYLMETHIONINE; SELENIUM; TAURINE; THIOCTIC ACID; UBIQUINONE; UNINDEXED DRUG; URSODEOXYCHOLIC ACID; VITAMIN B COMPLEX;

ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANTIOXIDANT ACTIVITY; BODY MASS; CELL PROTECTION; CHINESE MEDICINE; CLINICAL TRIAL; COMPARATIVE STUDY; CONFERENCE PAPER; DIET; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG POTENCY; DRUG SAFETY; DRUG TARGETING; EXERCISE; EXPERIMENTAL ANIMAL; EXPERIMENTAL RAT; HISTOPATHOLOGY; HUMAN; IMMUNOMODULATION; LIPID PEROXIDATION; LIVER BIOPSY; LOW CALORY DIET; NONALCOHOLIC FATTY LIVER; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; VITAMIN SUPPLEMENTATION; WEIGHT REDUCTION;

ACETYLCYSTEINE; ANTIOXIDANTS; BETAINE; CHOLAGOGUES AND CHOLERETICS; DISEASE PROGRESSION; FATTY LIVER; HUMANS; LIPID PEROXIDATION; S-ADENOSYLMETHIONINE; URSODEOXYCHOLIC ACID; VITAMIN E;

EID: 33748205007     PISSN: 01920790     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.mcg.0000168648.79034.67     Document Type: Conference Paper

References (101)

1. Browning J, Horton J. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004;114:147-152.
2. Unger R. Lipotoxic diseases. Annu Rev Med. 2002;53:319-336.
3. Recknagel RO, Glende EA, Britton RS. Free radical damage and lipid peroxidation. In: Meeks RG, Harrison SD, Bull RJ, eds. Hepatotoxicology. Boca Raton, FL: CRC Press, 1991:411.
4. Tilg H, Diehl A. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med. 2000;20:1467-1476.
5. Caldwell SH, Chang CY, Nakamoto RK, et al. The mitochondria in non-alcoholic fatty liver disease. Clin Liver Dis. 2004;8:595-617.
6. Le TH, Caldwell SH, Redick JA, et al. The zonal distribution of megamitochondria with crystalline inclusions in nonalcoholic steatohepatitis. Hepatology. 2004;39:1423-1429.
7. Feldstein AE, Canbay A, Angulo P, et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology. 2003;125:437-443.
8. Ribeiro PS, Cortez-Pinto HC, Sola S, et al. Hepatocyte apoptosis, expression of death receptors, and activation of NF-κB in the liver of nonalcoholic and alcoholic steatohepatitis patients. Am J Gastroenterol. 2004;99:1708-1717.
9. Brigelius Flohe R, Traber MG. Vitamin E: function and metabolism. FASEB J. 1999;13:1145-1155.
10. Kamal-Eldin A, Appelqvist L. The chemistry and antioxidant propoerties of tocopherols and tocotrienols. Lipids. 1996;31:671-701.
11. Saldeen T, Li D, Mehta JL. Differential effects of alpha- and gamma-tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis. J Am Coll Cardiol. 1999;34:1208-1215.
12. Liu M, Wallin R, Wallmon A, et al. Mixed tocopherols have a stronger inhibitory effect on lipid peroxidation than alpha-tocopherol alone. J Cardiovasc Pharm. 2002;39:714-721.
13. Chen H, Li D, Saldeen T, et al. Mixed tocopherol preparation is superior to alpha-tocopherol alone against hypoxia-reoxygenation injury. Biochem Biophys Res Commun. 2002;291:349-353.
14. Brigelius-Flohe R, Traber MG. Vitamin E: function and metabolism. FASEB J. 1999;13:1145-1155.
15. Liu M, Wallmon A, Olsson-Mortlock C, et al. Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms. Am J Clin Nutr. 2003;77:700-706.
16. Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. A Report of the Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Food Nutrition Board. Washington, DC: National Academies Pr, 2000.
17. Tappel AL. Vitamin E and selenium protection from in vivo lipid peroxidation. Ann NY Acad Sci. 1972;203:12-28.
18. Parola M, Muraca R, Dianzani I, et al. Vitamin E dietary supplementation inhibits tissue growth factor beta-1 gene expression in the rat liver. FEBS Lett. 1992;308:267-270.
19. Soltys K, Dikdan G, Konebu B. Oxidative stress in fatty livers of obese Zucker rats: rapid amelioration and improved tolerance to warm ischemia with tocopherol. Hepatology. 2001;34:13-18.
20. Parola M, Leonarduzzi G, Biasi F, et al. Vitamin E dietary supplementation protects against carbon tetracholoride-induced chronic liver damage and cirrhosis. Hepatology. 1992;16:1014-1021.
21. Sokol RJ, McKim JM Jr, Goff MC, et al. Vitamin E reduces oxidant injury to mitochondria and the hepatotoxicity of taurochenodeoxycholic acid in the rat. Gastroenterology. 1998;114:164-174.
22. Phung N, Farrell G, Robertson G. Vitamin E but not glutathione precursors inhibits hepatic fibrosis in experimental NASH exhibiting oxidative stress and mitochondrial abnormalities [Abstract]. Hepatology. 2001;34:361A.
23. Lavine JE. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr. 2000;136:734-738.
24. Hasegawa T, Yoneda M, Nakamura K, et al. Plasma transforming growth factor B-1 level and efficacy of α-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther. 2001;15:1667-1672.
25. Kugelmas M, Hill DB, Vivian B, et al. Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology. 2003;38:413-419.
26. Kawanaka M, Mahmood S, Niiyama G, et al. Control of oxidative stress and reduction in biochemical markers by Vitamin E treatment in patients with nonalcoholic steatohepatitis: a pilot study. Hepatol Res. 2004;29:39-41.
27. Vajro P, Mandato C, Franzese A, et al. Vitamin E treatment in pediatric obesity-related liver disease: a randomized study. J Pediatr Gastroenterol Nutr. 2004;38:48-55.
28. Harrison SA, Torgerson S, Hayashi P, et al. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2003;98:2485-2490.
29. Sanyal AJ, Mofrad PS, Contos MJ, et al. A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2004;2:1107-1115.
30. Miller ER, Barriuso RP, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37-46.
31. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, anti-oxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345:1583-1592.
32. Lieber CS. S-Adenosyl-L-methionine: its role in the treatment of liver disorders. Am J Clin Nutr. 2002;76(suppl):1183-1187.
33. Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench o the bedside- molecular basis of a pleiotrophic molecule. Am J Clin Nutr. 2002;76(suppl):1151-1157.
34. Alvaro D, Gigliozzi A, Piat C, et al. Effect of S-adenosyl-L-methionine on ethanol cholestasis and hepatotoxicity in isolated perfused rat liver. Dig Dis Sci. 1995;40:1592-1600.
35. Lu S. Methionine adenosyltransferase and liver disease: it's all about SAM. Gastroenterology. 1998;114:403-407.
36. Colell A. Garcia-Ruiz C, Morales A, et al. Transport of reduced glutathione in hepatic mitochondria and mitoplasts from ethanol-treated rats: effect of membrane physical properties and S-adenosyl-methionine. Hepatology. 1997;26:699-708.
37. Lieber CS. S-Adenosyl-L-methionine and alcoholic liver disease in animal models: Implications for early intervention in human beings. Alcohol. 2002;27:173-177.
38. Nakano H, Yamaguchi M, Kaneshiro Y, et al. S-Adenosyl-L-Methionine attenuates ischemia-reperfusion injury of steatotic rats. Transplant Proc. 1998;30:3735-3736.
39. Avila MA, Carretero MV, Rodriguez EN, et al. Regulation by hypoxia of methionine adenosyltransferase activity and gene expression in rat hepatocytes. Gastroenterology. 1998;114:364-371.
40. Duce AM, Ortiz P, Cabrero C, et al. S-Adenosyl-L-methionine synthetase and phospholipid methyltransferase are inhibited in human cirrhosis. Hepatology. 1988;8:65-68.
41. Chawla RK, Lewis FW, Kutner MH, et al. Plasma cysteine, cystine and glutathione in cirrhosis. Gastroenterology. 1984;87:770-776.
42. Lauterburg BH, Velez ME. Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity. Gut. 1988;29:1153-1157.
43. Sieger CP, Bossen KH, Yones M, et al. Glutathione and glutathione-S-transferases in he normal and diseased human liver. Pharmacol Res Commun. 1982;14:61-72.
44. Vendemiale G, Altomare E, Trizio T, et al. Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease. Scand J Gastroenterol. 1989;24:407-415.
45. Mazzanti R, Arcangeli A, Salvadori G, et al. The anti-steatotic effect of sulfo-adenosylmethionine (SAMe) in various forms of chronic hepatopathy: multicentric research. Minerva Med. 1978;69:3283-3292.
46. Labo G, Gasbarrini GB. Therapeutic action of S-adenosylmethionine in some chronic hepatopathies. Minerva Med. 1975;66:1563-1570.
47. Labo G, Gasbarrini G, Miglio F. Various effects of SAM dependent transmethylations in hepatology. Minerva Med. 1972;63:2007-2017.
48. Frezza M, Surrenti C, Manzillo G, et al. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis: a double-blind, placebo-controlled study. Gastroenterology. 1990;99:211-215.
49. Frezza M, Pozzato G, Chiesa L, et al. Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-L-methionine administration. Hepatology. 1984;4:274-278.
50. Mato JM, Camara J, Fernandez de Paz J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999;30:1081-1089.
51. Barak AJ, Beckenhauer HC, Tuma DJ. Betaine, ethanol, and the liver: a review. Alcohol. 1996;13:395-398.
52. Neuschwander-Tetri BA. Betaine: an old therapy for a new scourge. Am J Gastroenterol. 2001;96:2534-2546.
53. Houghton WC. Betaine and nonalcoholic steatohepatitis. Am J Gastroenterol. 2003;98:2803.
54. Barak AJ. Dietary betaine promotes generation of hepatic SAMe and rotects the liver from ethanol induced fatty infiltration. Alcohol Clin Exp Res. 1993;17:552-555.
55. Graf D, Kurz AK, Reinehr R, et al. Prevention of bile acid-induced apoptosis by betaine in rat liver. Hepatology. 2002;36:829-839.
56. Miglio F, Rovati LC, Santoro A, et al. Efficacy and safety of oral betaine glucuronate in non-alcoholic steatohepatitis: a double-blind, randomized, parallel-group, placebo-controlled prospective clinical study. Arzneimittelforschung. 2000;50:722-727.
57. Abdelmalek MF, Angulo P, Jorgensen RA, et al. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol. 2001;96:2711-2717.
58. Nakano H, Nagasaki H, Yoshida K, et al. N-Acetylcysteine and anti-ICAM-1 monoclonal antibody reduce ischemia-reperfusion injurt of the steatotic rat liver. Transplant Proc. 1998;30:3763.
59. Nakano H, Nagasaki H, Barama A, et al. The effect of N-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet. Hepatology. 1997;26:670-678.
60. Gulbahar O, Karasu ZA, Ersoz G, et al. Treatment of nonalcoholic steatohepatitis with N-acetylcysteine [Abstract]. Gastroenterology. 2000; 118:1444.
61. Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos. 2000;28:1270-1273.
62. Azuma Y, Shinohara M, Wang PL, et al. Histamine inhibits chemotaxis, phagocytosis, superoxide anion production, and the production of TNF-α and IL-12 by macrophages via H2-receptors. Int Immunopharmacol. 2001;1:1867-1875.
63. Villa RF, Gorini A. Pharmacology of lazaroids and brain energy metabolism: a review. Pharmacol Rev. 1997;49:99-136.
64. Li Z, Yang S, Lin H, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003;37:343-350.
65. Beuers U, Boyer JL, Paumgartner G. Ursodeoxycholic acid in cholestasis: potential mechanisms of action and therapeutic applications. Hepatology. 1998;28:1449-1453.
66. Bachrach WH, Hoffman AF. Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. Part I. Dig Dis Sci. 1982;27:737-761.
67. Trauner M, Graziadei IW. Review article: mechanisms of action and therapeutic applications of ursodeoxycholic acid in chronic liver diseases. Aliment Pharmacol Ther. 1999;13:979-996.
68. Iwasaki T. Uber die Konstitution der Ursodesoxycholsaure. Z Physiol Chem. 1936;244:181-193.
69. Lazaridis KN, Gores GJ, Lindor KD. Ursodeoxycholic acid: mechanisms of action and clinical use in hepatobiliary disorders. J Hepatol. 2001;35:134-146.
70. Hoffman AF. Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand J Gastroenterol. 1994;29(suppl 204):1-15.
71. Poupon RE, Poupon R, Balkau B. Ursodiol for the long-term treatment of primary biliary cirrhosis: the UDCA-PBC Study Group. N Engl J Med. 1994;330:1342-1347.
72. Lindor KD, Therneau TM, Jorgensen RA, et al. Effects of ursodeoxycholic acid on survival in patients with primary biliary cirrhosis. Gastroenterology. 1996;110:1515-1518.
73. Poupon RE, Lindor KD, Cauch-Dudek K, et al. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology. 1997;113:884-890.
74. Heuman DM, Pandak WM, Hylemon PB, et al. Conjugates of ursodeoxycholate protect against cytotoxicity of more hydrophobic bile salts: in vitro studies in rat hepatocytes and human erythrocytes. Hepatology. 1991;14:920-926.
75. Heuman DM, Bajaj R. Ursodeoxycholate conjugates protect against disruption of cholesterol-rich membranes by bile salts. Gastroenterology. 1994;106:1333-1341.
76. Heuman DM, Bajaj RS, Lin Q. Adsorption of mixtures of bile salt taurine conjugates to lecithin-cholesterol membranes: implications for bile salt toxicity and cytoprotection. J Lipid Res. 1996;37:562-573.
77. Rodrigues CM, Fan G, Ma X, et al. A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J Clin Invest. 1998;101:2790-2799.
78. Lukivskaya OY, Maskevich AA, Buko VU. Effect of ursodeoxycholic acid on prostaglandin metabolism and microsomal membranes in alcoholic fatty liver. Alcohol. 2001;25:99-105.
79. Tabouy L, Zamora AJ, Oliva L, et al. Ursodeoxycholate alleviates alcohol-induced liver mitochondrial injury [Abstract]. Gastroenterology. 1998;114:623.
80. Oliva L, Beague F, Choquant D, et al. Ursodeoxycholate alleviates alcoholic fatty liver damage in rats. Alcohol Clin Exp Res. 1998;22:1538-1543.
81. Okan A, Astarcioglu H, Tankurt E, et al. Effect of ursodeoxycholic acid on hepatic steatosis in rats. Dig Dis Sci. 2002;47:2389-2397.
82. Laurin J, Lindor KD, Crippen JS, et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. Hepatology. 1996;23:1464-1467.
83. Guma G, Viola L, Thome M, et al. Ursodeoxycholic acid in the treatment of nonalcoholic steatohepatitis: results of a prospective clinical controlled trial [Abstract]. Hepatology. 1997;26:387.
84. Ceriani R, Brunati S, Morini L, et al. Effect of ursodeoxycholic acid plus diet in patients with nonalcoholic steatohepatitis [Abstract]. Hepatology. 1998;28:386.
85. Mendez-Sanchez N, Gonzalez V, Pichardo-Bahena R, et al. Weight reduction and ursodeoxycholic acid in subjects with nonalcoholic fatty liver disease: a double-blind, randomized, placebo-controlled trial [Abstract]. Hepatology. 2000;32:412A.
86. Santos VN, Lanzoni VP, Szenfel J, et al. A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid. Braz J Med Biol Res. 2003;36:723-729.
87. Bauditz J, Schmidt J, Dippe P, et al. Non-alcohol induced steatohepatitis in non-obese patients: treatment with ursodeoxycholic acid. Am J Gastroenterol. 2004;99:959-960.
88. Lindor KD, Kowdley KV, Heathcote EJ, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004;39:770-778.
89. Clark JM, Brancati FL. Negative trials in nonalcoholic steatohepatitis: why they happen and what they teach us. Hepatology. 2004;39:602-603.
90. Nguyen-Duy TB, Nichaman MZ, Church TS, et al. Visceral fat and liver fat are independent predictors of metabolic risk factors in men. Am J Physiol Endocrinol Metab. 2003;284:E1065-E1071.
91. Ratziu V, Charlotte F, Heurtier A, et al. High sampling variability of percutaneous liver biopsy in non-alcoholic fatty liver disease [Abstract]. Hepatology. 2004;40:236A.
92. Kerai MD, Waterfield CJ, Kenyon SH, et al. The effect of taurine depletion by b-alanine treatment on the susceptibility to ethanol-induced hepatic dysfunction in rats. Alcohol Alcohol. 2001;36:29-38.
93. Kerai MD, Waterfield CJ, Kenyon SH, et al. Reversal of ethanol-induced hepatic steatosis and lipid peroxidation by taurine: a study in rats. Alcohol Alcohol. 1999;34:529-541.
94. Zaman N, Tam YK, Jewell LD, et al. Effects of taurine supplementation in parenteral nutrition-associated hepatosteatosis and lidocaine metabolism. A study using isolated rat liver perfusion. Drug Metab Dispos. 1996;24:534-541.
95. Kerai MD, Waterfield CJ, Kenyon SH, et al. Taurine: protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats. Amino Acids. 1998;15:53-76.
96. Obinata K, Maruyama T, Hayashi M, et al. Effect of taurine on the fatty liver of children with simple obesity. Adv Exp Med Biol. 1996;403:607-613.
97. Simon JB, Scheig R, Klatskin G. Protection by orotic acid against the renal necrosis and fatty liver of choline deficiency. Proc Soc Exp Biol Med. 1968;129:874-877.
98. Buchman AL, Dubin M, Jenden D, et al. Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. Gastroenterology. 1992;102:1363-1370.
99. Demetriou AA. Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. JPEN. 1992;16:487-488.
100. Kelly JP, Kaufman DW, Kelley K, et al. Recent trends in use of herbal and other natural products. Arch Intern Med. 2005;165:281-286.
101. Hathcock J. Dietary supplements: how they are used and regulated. J Nutr. 2001;131(suppl):1114-1117.