Curcumin reduces oxidative and nitrative DNA damage through balancing of oxidant-antioxidant status in hamsters infected with Opisthorchis viverrini.
Opisthorchis viverrini (OV) infection is endemic in northeastern Thailand. We have previously reported that OV infection induces oxidative and nitrative DNA damage via chronic inflammation, which contributes to the disease and cholangiocarcinogenesis. Here, we examined the effect of curcumin, an antioxidant, on pathogenesis in OV-infected hamsters. DNA lesions were detected by double immunofluorescence and the hepatic expression of oxidant-generating and antioxidant genes was assessed by quantitative RT-PCR analysis. Dietary 1.0% curcumin significantly decreased OV-induced accumulation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidative DNA lesion, and 8-nitroguanine, a nitrative DNA lesion, in the nucleus of bile duct epithelial and inflammatory cells. Expression of oxidant-generating genes (inducible nitric oxide synthase; iNOS, its nuclear transcriptional factor, NF-kappaB, and cyclooxygenase-2), and plasma levels of nitrate, malondialdehyde, and alanine aminotransferase, were also decreased in curcumin-treated group. In contrast, curcumin increased the mRNA expression of antioxidant enzymes (Mn-superoxide dismutase and catalase), and ferric-reducing anti-oxidant power in the plasma. In conclusion, curcumin reduced oxidative and nitrative DNA damage by suppression of oxidant-generating genes and enhancement of antioxidant genes, leading to inhibition of oxidative and nitrative stress. Therefore, curcumin may be used as a chemopreventive agent to reduce the severity of OV-associated diseases and the risk of cholangiocarcinoma (CCA).
Pinlaor
Somchai
S
Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. psomec@kku.ac.th
Yongvanit
Puangrat
P
Prakobwong
Suksanti
S
Kaewsamut
Butsara
B
Khoontawad
Jarinya
J
Pinlaor
Porntip
P
Hiraku
Yusuke
Y
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D003474:Curcumin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008315:Malondialdehyde / Q000097:blood; D008647:Mesocricetus; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009889:Opisthorchiasis / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D009891:Opisthorchis / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D010270:Parasite Egg Count; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D016587:Antimutagenic Agents; D016328:NF-kappa B; D009566:Nitrates; D018809:Proliferating Cell Nuclear Antigen; D008315:Malondialdehyde; D002374:Catalase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D003474:Curcumin