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Melatonin inhibits cholangiocarcinoma and reduces liver injury in Opisthorchis viverrini-infected and N-nitrosodimethylamine-treated hamsters.
- Source :
-
Journal of pineal research [J Pineal Res] 2013 Oct; Vol. 55 (3), pp. 257-66. Date of Electronic Publication: 2013 Jun 15. - Publication Year :
- 2013
-
Abstract
- The human liver fluke Opisthorchis viverrini infection and N-nitrosodimethylamine (NDMA) administration induce cholangiocarcinoma (CCA) and liver injury in hamsters. Melatonin protects against liver injury and reduces the alteration of mitochondrial structure, mitochondrial membrane potential, and mitochondrial pro- and anti-apoptotic pathways in various cancer types. To investigate the chemopreventive effect of melatonin on CCA genesis and liver injury, hamsters were treated with a combination of O. viverrini infection and NDMA concurrently administered with melatonin (10 mg/kg and 50 mg/kg) for 120 days. Melatonin treatment at 50 mg/kg caused a significant reduction in liver/body weight ratios and decreased tumor volumes leading to an increase in the survival of animals. In the tumorous tissues, the high-dose melatonin reduced DNA fragmentation and mitochondrial apoptosis by inducing anti-apoptotic protein (Bcl-2) in the mitochondrial fraction and down-regulating cytochrome c, pro-apoptotic protein (Bax), and caspase-3 in tumor cytosol. Moreover, a high-dose melatonin treatment significantly increased mitochondrial antioxidant enzymes and prevented mitochondrial ultrastructure changes in the tumor. Overall, melatonin has potent chemopreventive effects in inhibiting CCA genesis and also reduces liver injury in hamster CCA, which, in part, might involve in the suppression of CCA by reducing tumor mitochondria alteration.<br /> (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Animals
Cholangiocarcinoma etiology
Cholangiocarcinoma metabolism
Cholangiocarcinoma ultrastructure
Cricetinae
DNA Fragmentation drug effects
DNA, Neoplasm metabolism
Dimethylnitrosamine toxicity
Humans
Liver pathology
Liver Neoplasms etiology
Liver Neoplasms metabolism
Liver Neoplasms ultrastructure
Male
Mesocricetus
Mitochondria, Liver metabolism
Mitochondria, Liver ultrastructure
Neoplasm Proteins metabolism
Opisthorchiasis complications
Time Factors
Antioxidants pharmacology
Cholangiocarcinoma prevention & control
Liver metabolism
Liver Neoplasms prevention & control
Melatonin pharmacology
Opisthorchis
Subjects
Details
- Language :
- English
- ISSN :
- 1600-079X
- Volume :
- 55
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of pineal research
- Publication Type :
- Academic Journal
- Accession number :
- 23772655
- Full Text :
- https://doi.org/10.1111/jpi.12068