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Publication
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| Title of Article |
Antifibrotic effect of xanthohumol in combination with praziquantel is associated with altered redox status and reduced iron accumulation during liver fluke-associated cholangiocarcinogenesis |
| Date of Acceptance |
29 December 2017 |
| Journal |
| Title of Journal |
PeerJ |
| Standard |
ISI |
| Institute of Journal |
PeerJ |
| ISBN/ISSN |
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| Volume |
2018 |
| Issue |
6 |
| Month |
January |
| Year of Publication |
2018 |
| Page |
e4281 |
| Abstract |
Cholangiocarcinoma (CCA) caused by infection of the liver fluke Opisthorchis viverrini,
(Ov) is the major public health problem in northeast Thailand. Following Ov infection
the subsequent molecular changes can be associated by reactive oxygen species (ROS)
induced chronic inflammation, advanced periductal fibrosis, and cholangiocarcino-
genesis. Notably, resistance to an activation of cell death in prolonged oxidative stress
conditions can occur but some damaged/mutated cells could survive and enable
clonal expansion. Our study used a natural product, xanthohumol (XN), which
is an anti-oxidant and anti-inflammatory compound, to examine whether it could
prevent Ov-associated CCA carcinogenesis. We measured the effect of XN with or
without praziquantel (PZ), an anti-helminthic treatment, on DNA damage, redox
status change including iron accumulation and periductal fibrosis during CCA genesis
induced by administration of Ov and N-dinitrosomethylamine (NDMA) in hamsters.
Animals were randomly divided into four groups: group I, Ov infection and NDMA
administration (ON); group II, Ov infection and NDMA administration and PZ
treatment (ONP); the latter 2 groups were similar to group I and II, but group III
received additional XN (XON) and group IV received XN plus PZ (XONP). The
results showed that high 8-oxodG (a marker ofDNAdamage) was observed throughout
cholangiocarcinogenesis. Moreover, increased expression of CD44v8-10 (a cell surface
in regulation of the ROS defense system), whereas decreased expression of phospho-
p38MAPK (a major ROS target), was found during the progression of the bile duct cell
transformation. In addition, high accumulation of iron and expression of transferrin
receptor-1 (TfR-1) in both malignant bile ducts and inflammatory cells were detected.
Furthermore, fibrosis also increased with the highest level being on day 180. On the
other hand, the groups of XN with or without PZ supplementations showed an effective
reduction in all the markers examined, including fibrosis when compared with the ON
group. In particular, the XONP group, in which a significant reduction DNA damage |
| Keyword |
Cholangiocarcinoma, Oxidative stress, DNA damage, Iron, Chemoprevention, Fibrosis |
| Author |
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| Reviewing Status |
มีผู้ประเมินอิสระ |
| Status |
ตีพิมพ์แล้ว |
| Level of Publication |
นานาชาติ |
| citation |
true |
| Part of thesis |
true |
| Attach file |
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| Citation |
0
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Journal Publication
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