High excretion of etheno adducts in liver fluke-infected patients: protection by praziquantel against DNA damage.
Chronic infection by Opisthorchis viverrini (OV) is a strong risk factor for developing cholangiocarcinoma (CCA). To clarify the involvement of oxidative stress and lipid peroxidation (LPO)-derived DNA damage, the excretion of LPO-derived etheno DNA adducts was measured in urine samples collected from healthy volunteers and OV-infected Thai subjects. 1,N(6)-etheno-2'-deoxyadenosine (epsilondA) and 3,N(4)-etheno-2'-deoxycytidine (epsilondC) levels were quantified by immunoprecipitation/high-performance liquid chromatography/fluorescence detection and (32)P-postlabeling TLC. Excreted etheno adduct levels were related to indicators of inflammatory conditions [malondialdehyde (MDA) and nitrate/nitrite levels in urine and plasma alkaline phosphatase (ALP) activity]. Mean epsilondA and epsilondC levels were 3 to 4 times higher in urine of OV-infected patients; MDA, nitrate/nitrite, and ALP were also increased up to 2-fold. MDA and ALP were positively related to epsilondA excretion. Two months after a single dose of the antiparasitic drug Praziquantel, epsilondA and epsilondC concentrations in urine of OV-infected subjects were decreased; MDA, nitrate/nitrite, and ALP were concomitantly lowered. We conclude that chronic OV infection through oxidative/nitrative stress leads to increased urinary excretion of the etheno-bridged deoxyribonucleosides, reflecting high LPO-derived DNA damage in vivo. These promutagenic DNA etheno adducts in bile duct epithelial cells may increase the risk of OV-infected patients to later develop CCA. Urinary epsilondA and epsilondC levels should be explored (a) as noninvasive risk markers for developing opisthorchiasis-related CCA and (b) as promising biomarkers to assess the efficacy of preventive and therapeutic interventions.
Dechakhamphu
Somkid
S
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Yongvanit
Puangrat
P
Nair
Jagadeesan
J
Pinlaor
Somchai
S
Sitthithaworn
Paiboon
P
Bartsch
Helmut
H
D000328:Adult; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001650:Bile Duct Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000652:urine*; D004249:DNA Damage / Q000187:drug effects*; D003839:Deoxyadenosines / Q000652:urine*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000652:urine; D005243:Feces / Q000469:parasitology; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009889:Opisthorchiasis / Q000150:complications / Q000453:epidemiology / Q000652:urine*; D009891:Opisthorchis / Q000302:isolation & purification; D018384:Oxidative Stress; D011223:Praziquantel / Q000494:pharmacology*; D012307:Risk Factors; D013785:Thailand / Q000453:epidemiology
D000871:Anthelmintics; D018736:DNA Adducts; D003839:Deoxyadenosines; D003841:Deoxycytidine; D011223:Praziquantel; C032221:1,N(6)-ethenodeoxyadenosine; C032222:3,N(4)-ethenodeoxycytidine