Serum and liver micronutrient antioxidants and serum oxidative stress in patients with chronic hepatitis C.
OBJECTIVE
The exact pathogenesis of liver injury and fibrosis in chronic hepatitis C (CHC) is unclear. Free radicals play a role in CHC liver damage. Antioxidants (AO) (enzymatic and nonenzymatic) scavenge free radicals and prevent tissue injury. The aims of our study were to estimate serum levels of malondialdehyde (MDA), serum and liver levels of nonenzymatic fat-soluble AO, and to correlate the liver AO levels with the degree of inflammation and fibrosis on biopsy.


METHODS
AO levels were estimated by high-pressure liquid chromatography in the pretreatment serum and liver biopsy specimen of 20 treatment-naïve patients with CHC who were not on vitamin supplements. Serum levels of MDA were measured as a marker of increased oxidative stress. Twenty-two healthy individuals with no history of vitamin supplementation served as controls. AO analyzed were: retinol, alpha- and gamma-tocopherol, lutein, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene.


RESULTS
Twenty CHC patients (11 men, nine women, mean age 48.5 +/- 7.9 yr) were studied. Patients and controls were comparable in age and sex. Serum MDA levels were significantly higher in CHC patients compared with controls (1.62 +/- 0.57 vs 0.23 +/- 0.15 micromol/L, p = < 0.0000). Serum levels of all AO except lutein were significantly decreased in CHC patients, and their levels were two to ten times lower than serum levels in controls. Liver levels of alpha-carotene (p = 0.0004), beta-carotene (p = 0.006), and lutein (p = 0.002) correlated with the serum levels, whereas the levels of retinol, alpha-tocopherol, lycopene, and beta-cryptoxanthin showed no correlation. Serum MDA levels were significantly higher in patients with moderate-to-severe inflammation or fibrosis compared with those with mild inflammation or fibrosis. The levels of all liver AO except alpha-carotene were significantly lower in patients with moderate-to-severe fibrosis. The severity of inflammation (portal or lobular) did not affect liver AO levels.


CONCLUSIONS
Our findings suggest that increased oxidative stress is present in patients with CHC. Micronutrient AO are severely depleted in serum and liver tissue of patients with CHC, and liver levels of some AO appear to reflect serum levels. Increasing fibrosis is associated with decreased liver AO levels indicating that severe disease may be a consequence of AO depletion or decreased liver storage resulting from fibrosis.
Yadav
Dhiraj
D
Department of Biomedical Research, Our Lady of Mercy University Medical Center, New York Medical College, Bronx 10466, USA.
Hertan
Hilary I
HI
Schweitzer
P
P
Norkus
E P
EP
Pitchumoni
C S
CS
D000328:Adult; D000975:Antioxidants / Q000032:analysis*; D002338:Carotenoids / Q000032:analysis; D065366:Cryptoxanthins; D005260:Female; D005355:Fibrosis; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D014975:Lutein / Q000032:analysis; D000077276:Lycopene; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018977:Micronutrients / Q000032:analysis; D008875:Middle Aged; D018384:Oxidative Stress; D024505:Tocopherols / Q000032:analysis; D014801:Vitamin A / Q000032:analysis; D024341:Xanthophylls; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000032:analysis
D000975:Antioxidants; D065366:Cryptoxanthins; D018977:Micronutrients; D024341:Xanthophylls; D019207:beta Carotene; D014801:Vitamin A; D002338:Carotenoids; D008315:Malondialdehyde; D024505:Tocopherols; D000077276:Lycopene; D014975:Lutein