| Popis: |
Background: Curcumin-loaded nanocomplexes (CNCs) previously demonstrated lower toxicity and extended release better than is the case for free curcumin. Here, we evaluated the efficacy of CNCs against opisthorchiasis-associated cholangiocarcinoma (CCA) in hamsters. Method: Dose optimization (dose and frequency) was performed over a one-month period using hamsters, a model that is widely used for study of opisthorchiasis-associated cholangiocarcinoma. In the main experimental study, CCA was induced by a combination of fluke, Opisthorchis viverrini (OV), infection and N-nitrosodimethylamine (NDMA) treatment. Either blank (empty) nanocomplexes (BNCs) or different concentrations of CNCs (equivalent to 10 and 20 mg cur/kg bw) were given to hamsters thrice a week for five months. The histopathological changes, biochemical parameters, and the expression of inflammatory/ oncogenic transcription factors were investigated.Results: The optimization study revealed that treatment with CNCs at a dose equivalent to 10 mg cur/kg bw, thrice a week for one month, led to a greater reduction of inflammation and liver injury induced in hamsters by OV+NDMA than did treatments at other dose rates. Oral administration with CNCs (10 mg cur/kg bw), thrice a week for five months, significantly increased survival rate, reduced CCA incidence, extent of tumor development, cholangitis, bile-duct injury and cholangiofibroma. In addition, this treatment decreased serum ALP and ALT levels and suppressed expression of oncogenic transcription factors including NF- κB and FOXM1. Conclusion: CNCs (10 mg cur/kg bw) attenuate the progression of fluke-related CCA in hamsters. |
