Lipid peroxidation and etheno DNA adducts in white blood cells of liver fluke-infected patients: protection by plasma alpha-tocopherol and praziquantel.
Chronic infection by the liver fluke Opisthorchis viverrini is a strong risk factor for cholangiocarcinoma. To clarify the involvement of oxidative stress and lipid peroxidation-derived DNA damage, etheno (epsilon)-DNA adducts (epsilondA, epsilondC) in WBC and plasma alpha-tocopherol were measured in samples collected from O. viverrini-infected Thai patients (n = 50) and healthy noninfected volunteers (n = 20). epsilondA and epsilondC levels were three to five times higher (P < 0.001) in infected patients than in controls; O. viverrini infection also increased two to three times in the plasma inflammatory indicators, 8-isoprostane, malondialdehyde, and nitrate/nitrite. Mean plasma alpha-tocopherol levels were two times lower in patients than in healthy controls (P < 0.001). Two months after a single dose to infected patients of the antiparasitic drug praziquantel, epsilondA and epsilondC levels in WBC were decreased to control level (P < 0.03); plasma 8-isoprostane, malondialdehyde, nitrate/nitrite, and alkaline phosphatase (ALP) were concomitantly lowered. epsilondA and epsilondC levels in WBC were positively correlated with plasma 8-isoprostane, malondialdehyde, and nitrate/nitrite levels and ALP activity, whereas plasma alpha-tocopherol levels showed inverse correlations. We conclude that chronic O.viverrini infection induces an accumulation of lipid peroxidation-derived DNA damage through oxidative/nitrative stress, which is lowered by the plasma alpha-tocopherol and by antiparasitic drug therapy. Etheno adducts in WBC and urine should be explored as a risk marker for opisthorchiasis-related cholangiocarcinoma, and to assess the efficacy of preventive and therapeutic interventions.
Dechakhamphu
Somkid
S
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Pinlaor
Somchai
S
Sitthithaworn
Paiboon
P
Nair
Jagadeesan
J
Bartsch
Helmut
H
Yongvanit
Puangrat
P
D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000097:blood / Q000469:parasitology / Q000517:prevention & control; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000469:parasitology; D018281:Cholangiocarcinoma / Q000097:blood / Q000469:parasitology / Q000517:prevention & control; D018736:DNA Adducts / Q000097:blood* / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D009889:Opisthorchiasis / Q000097:blood* / Q000188:drug therapy; D009891:Opisthorchis; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011223:Praziquantel / Q000627:therapeutic use*; D024502:alpha-Tocopherol / Q000097:blood*
D000871:Anthelmintics; D018736:DNA Adducts; D009566:Nitrates; D009573:Nitrites; C075750:8-epi-prostaglandin F2alpha; D008315:Malondialdehyde; D011223:Praziquantel; D015237:Dinoprost; D024502:alpha-Tocopherol