Oxidative-inflammatory damage in cirrhosis: effect of vitamin E and a fermented papaya preparation.
OBJECTIVE
Oxidative DNA damage occurs as an early event in hepatitis C virus (HCV) infection and is an indication of the potential for carcinogenesis. The aim of this study was to test a novel antioxidant/immunomodulator in patients with HCV-related cirrhosis.


METHODS
The study group consisted of 50 patients with HCV-related cirrhosis with transaminase values less than twofold increased (alanine aminotransferase [ALT] < 80 IU/L). Patients underwent a standardized food-vitamin composition assessment and were assessed for dietary intake, nutritional status and iron level. Patients were randomly allocated into two groups and then given either alpha-tocopherol 900 IU/day or 9 g/day of a fermented papaya preparation (FPP, Immun-Age, Osato Research Institute, Gifu, Japan) at bedtime for 6 months. Ten healthy subjects served as controls. Patients were checked monthly for: routine tests, redox status (reduced glutathione, glutathione peroxidase, oxidized glutathione, malondialdehyde), plasma alpha-tocopherol, 8-hydroxy-deoxy-guanidine (8-OHdG) level in circulating leukocyte DNA and serum levels of cytokines.


RESULTS
Patients with cirrhosis showed a significant imbalance of redox status (low antioxidants/high oxidative stress markers) (P < 0.005 vs controls). Neither treatment regimen affected transaminases as a whole. However, vitamin E supplementation almost normalized ALT only in the limited vitamin-E-deficient subgroup. A significant improvement of redox status was obtained by both regimens. However, only FPP significantly decreased 8-OHdG and the improvement of cytokine balance with FPP was significantly better than with vitamin E treatment (P < 0.05).


CONCLUSIONS
Although the present data seem to suggest a potential supportive role of antioxidants/immunomodulators as FPP in HCV patients, more studies are needed to substantiate their effect on the natural history of the disease.
Marotta
Francesco
F
Hepatogastroenterology Department, S. Giuseppe Hospital, Milan, Italy. fmarchimede@libero.it
Yoshida
Chisato
C
Barreto
Rafael
R
Naito
Yasuhiro
Y
Packer
Lester
L
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D029441:Carica; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005285:Fermentation; D005638:Fruit; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase; D006526:Hepatitis C / Q000097:blood / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D028321:Plant Preparations / Q000494:pharmacology / Q000627:therapeutic use*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D024502:alpha-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D007155:Immunologic Factors; D028321:Plant Preparations; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005979:Glutathione Peroxidase; D000410:Alanine Transaminase; D003849:Deoxyguanosine; D005978:Glutathione; D024502:alpha-Tocopherol