8-hydroxy-2--deoxyguanosine and Hepatitis--Viral--Human

Oxidative stress plays a role in pathogenesis of chronic viral hepatitis. Expression of oxidative stress-related molecules remains to be clarified.. 4-hydroxy-2-nonenal (4-HNE), 4-hydroxy-2-hexenal (4-HHE), catalase, superoxide dismutase-1 (SOD-1), glutathione peroxidase-1, thioredoxin (TRX) in leukocytes and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) were examined in 164 persons, including 130 chronic viral hepatitis patients and 34 normal individuals, by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Hepatic expression of these proteins was immunohistochemically examined in 12 patients with chronic viral hepatitis, compared with three persons without liver damage.. The 4-HNE/beta-actin ratios in chronic viral hepatitis were significantly higher than those in normal individuals (P<0.01), and were significantly correlated with asparate aminotransferase (AST) and alanine aminotransferase (ALT) (P<0.01, each). The catalase/beta-actin and SOD-1/beta-actin ratios in chronic viral hepatitis were higher than those in normal individuals, and were significantly correlated with 4-HNE/beta-actin ratios (P<0.01, each). Hepatic expression of 4-HNE, 4-HHE, catalase, SOD-1 and TRX in chronic viral hepatitis was higher than that without liver damage. Urinary excretion of 8-OHdG was not changed in chronic viral hepatitis.. The results of the present study suggest that expression of oxidative stress-related molecules in leukocytes is upregulated in relation to serum aminotransferase levels.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Alanine Transaminase; Aldehydes; Aspartate Aminotransferases; Blotting, Western; Deoxyguanosine; Enzyme-Linked Immunosorbent Assay; Enzymes; Female; Hepatitis, Viral, Human; Humans; Leukocytes; Lipid Peroxidation; Liver; Male; Middle Aged; Oxidative Stress; Thioredoxins; Up-Regulation

Urinary 8-hydroxydeoxyguanosine (8-OHdG) DNA adduct has been used as a biomarker in epidemiological studies. However, the determinants for urinary 8-OHdG have not been clearly identified. We tested urinary 8-OHdG levels in 205 male workers who had been exposed to vinyl chloride monomer (VCM). Epidemiological information was obtained by an interviewer-administered questionnaire. Hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody (anti-HCV) were also determined by immunoassay. Plasma antioxidants including Vitamins A and E, alpha- and beta-carotenes were assayed by high performance liquid chromatography. Median of urinary 8-OHdG level was 9.8 ng/mg creatinine (range, 1.4-60.1). Multiple linear regression analysis showed that alcohol drinkers had higher urinary 8-OHdG than those who did not, but there was no dose-response between the amount of alcohol consumption and urinary 8-OHdG. Workers with positive HBsAg, anti-HCV and elevated plasma Vitamin A level were independently associated with higher levels of urinary 8-OHdG, whereas age, smoking, body mass index, plasma alpha- and beta-carotenes, Vitamin E levels, or VCM exposure did not show such an association. The results suggest that active inflammation of hepatitis B and C, alcohol consumption and higher Vitamin A level can induce oxidative stress. Thus, we conclude that potential determinants need to be considered in epidemiological studies when urinary 8-OHdG is used as a biomarker.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Alcohol Drinking; Carcinogens; Deoxyguanosine; Hepatitis, Viral, Human; Humans; Male; Occupational Exposure; Vinyl Chloride; Vitamin A