Systemic Markers of Lipid Peroxidation and Antioxidants in Patients with Nonalcoholic Fatty Liver Disease

OBJECTIVES:The aim of the present study was to examine the systemic parameters of oxidative stress and antioxidants in patients with nonalcoholic fatty liver disease and investigate the relationship between these parameters and clinical and biochemical outcomes.METHODS:Fifty-one male patients with nonalcoholic fatty liver disease (group I), 30 age-matched and body mass index (BMI)-matched healthy male subjects, and 30 age-matched male patients with chronic viral hepatitis (group II) were enrolled in the study.RESULTS:Increased systemic levels of malondialdehyde and depletion of antioxidants such as coenzyme Q10, CuZn-superoxide dismutase, and catalase activity were observed in group I. Coenzyme Q10 and CuZn-superoxide dismutase correlated negatively with increasing necroinflammatory activity and fibrosis. Body fat was negatively associated with plasma coenzyme Q10 levels, while an inverse association was found between plasma catalase levels and TG. However, LDL was positively associated with plasma malondialdehyde levels. CuZn-superoxide dismutase levels were negatively associated with glucose, insulin, and HOMA-IR. In addition, the levels of CuZn-superoxide dismutase correlated significantly in a negative manner with BMI.CONCLUSIONS:Our results concerning correlations suggest that disturbances in BMI, body fat, and lipid metabolism may contribute to altered oxidative status in NAFLD, and insulin resistance may be related to decreased antioxidants in NAFLD as well as products of lipid peroxidation. However, although our results suggest interesting correlations, this different mostly “weak” relationships must be taken with caution.

[1]  N. Chalasani,et al.  Systemic Levels of Lipid Peroxidation and Its Metabolic and Dietary Correlates in Patients with Nonalcoholic Steatohepatitis , 2004, American Journal of Gastroenterology.

[2]  E. Fisher,et al.  Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production. , 2004, The Journal of clinical investigation.

[3]  J. Tran van Nhieu,et al.  Pivotal role of superoxide anion and beneficial effect of antioxidant molecules in murine steatohepatitis , 2004, Hepatology.

[4]  R. Rodrigo,et al.  Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. , 2004, Clinical science.

[5]  C. Sempoux,et al.  Oxidative stress, KLF6 and transforming growth factor-beta up-regulation differentiate non-alcoholic steatohepatitis progressing to fibrosis from uncomplicated steatosis in rats. , 2003, Journal of hepatology.

[6]  M. Charlton,et al.  Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis , 2003, Hepatology.

[7]  S. Yılmaz,et al.  Levels of plasma malondialdehyde and erythrocyte antioxidant enzyme activities in patients with chronic hepatitis B. , 2003, Hepato-gastroenterology.

[8]  J. Oppert,et al.  Increase of liver anti-oxidant enzyme activities in non-alcoholic steatohepatitis (NASH): A defense against an oxidative stress , 2003 .

[9]  M. Yılmaz,et al.  Increased oxidative stress and hypozincemia in male obesity. , 2002, Clinical biochemistry.

[10]  D. V. van Thiel,et al.  Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. , 2002, Nutrition reviews.

[11]  S. Seki,et al.  In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases. , 2002, Journal of hepatology.

[12]  D. Pessayre,et al.  Nonalcoholic steatosis and steatohepatitis. V. Mitochondrial dysfunction in steatohepatitis. , 2002, American journal of physiology. Gastrointestinal and liver physiology.

[13]  Frank Scholle,et al.  Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. , 2002, Gastroenterology.

[14]  N. Ballatori,et al.  Novel roles for glutathione in gene expression, cell death, and membrane transport of organic solutes. , 2001, Journal of hepatology.

[15]  P. Ward,et al.  Lipid peroxidation in hepatic steatosis in humans is associated with hepatic fibrosis and occurs predominately in acinar zone 3 , 2001, Journal of gastroenterology and hepatology.

[16]  J. Clore,et al.  Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. , 2001, Gastroenterology.

[17]  P. Portincasa,et al.  Oxidative stress in symptom‐free HCV carriers: relation with ALT flare‐up , 2001, European journal of clinical investigation.

[18]  I. Leclercq,et al.  CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis. , 2000, The Journal of clinical investigation.

[19]  B. Neuschwander‐Tetri,et al.  Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions , 1999, American Journal of Gastroenterology.

[20]  S. Toyokuni.  Reactive oxygen species‐induced molecular damage and its application in pathology , 1999, Pathology international.

[21]  J. Knight.  Free radicals: their history and current status in aging and disease. , 1998, Annals of clinical and laboratory science.

[22]  D. Pessayre,et al.  Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. , 1998, Gastroenterology.

[23]  Å. Danielsson,et al.  Effects of vitamins E, C and catalase on bromobenzene- and hydrogen peroxide-induced intracellular oxidation and DNA single-strand breakage in Hep G2 cells. , 1997, Journal of hepatology.

[24]  M. Weltman,et al.  Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation. , 1996, Gastroenterology.

[25]  R. Stocker,et al.  Cosupplementation with coenzyme Q prevents the prooxidant effect of alpha-tocopherol and increases the resistance of LDL to transition metal-dependent oxidation initiation. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[26]  D. Pessayre,et al.  Acute and chronic hepatic steatosis lead to in vivo lipid peroxidation in mice. , 1996, Journal of hepatology.

[27]  T. Kawasaki,et al.  Antioxidant role of cellular reduced coenzyme Q homologs and alpha-tocopherol in free radical-induced injury of hepatocytes isolated from rats fed diets with different vitamin E contents. , 1992, Biochimica et biophysica acta.

[28]  G. Siest,et al.  Biological variability of superoxide dismutase, glutathione peroxidase, and catalase in blood. , 1991, Clinical chemistry.

[29]  L. Wittmers,et al.  Influence of genetic obesity, food intake and adrenalectomy in mice on selected trace element-dependent protective enzymes. , 1988, Journal of NutriLife.

[30]  G. Poli,et al.  The role of lipid peroxidation in liver damage. , 1987, Chemistry and physics of lipids.

[31]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[32]  W. Weglicki,et al.  Differential Sensitivity of Canine Cardiac Sarcolemmal and Microsomal Enzymes to Inhibition by Free Radical‐Induced Lipid Peroxidation , 1984, Circulation research.

[33]  Neil Kaplowitz,et al.  Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis , 1981, Hepatology.

[34]  H. Theorell,et al.  Ubiquinone and α-tocopherol in plasma; means of translocation or depot , 2004, The clinical investigator.

[35]  M. Koruk,et al.  Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis. , 2004, Annals of clinical and laboratory science.

[36]  J. Yodoi,et al.  Serum thioredoxin levels as a predictor of steatohepatitis in patients with nonalcoholic fatty liver disease. , 2003, Journal of hepatology.

[37]  D. Pessayre,et al.  Mitochondria in Steatohepatitis , 2001, Seminars in liver disease.

[38]  J. Mckenney,et al.  Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). , 2001, JAMA.

[39]  M. L. Genova,et al.  Oxidative stress, antioxidant defences and aging , 1998, BioFactors.

[40]  R. E. Beyer.  The participation of coenzyme Q in free radical production and antioxidation. , 1990, Free radical biology & medicine.

[41]  G. Vendemiale,et al.  Hepatic glutathione content in patients with alcoholic and non alcoholic liver diseases. , 1988, Life sciences.

[42]  B. Tabachnick,et al.  Using Multivariate Statistics , 1983 .