Mito-TEMPO, a mitochondria-targeted antioxidant, prevents Nnitrosodiethylamine-induced hepatocarcinogenesis in mice

Shetty, Sachin and Kumar, Rajesh and Bharati, Sanjay (2019) Mito-TEMPO, a mitochondria-targeted antioxidant, prevents Nnitrosodiethylamine-induced hepatocarcinogenesis in mice. Free Radical Biology and Medicine, 136 (7). pp. 76-86. ISSN 0891-5849

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Abstract

Background: Oxidative stress and mitochondrial dysfunction play a significant role in hepatocarcinogenesis.Mitochondria are source organelle as well as target for free radicals. The oxidative damage to mitochondria can be prevented by mitochondria-targeted antioxidant, mito-TEMPO. However, its efficacy in prevention of hepatocellular carcinoma has not been investigated so far.Methods: Murine model of hepatocarcinogenesis was developed by intraperitoneal administration of N-nitrosodiethylamine to male BALB/c mice. Mito-TEMPO was administered intraperitoneally at weekly intervals,till the completion of the study. The tumours were histopathologically analysed and anti-cancer efficacy of mito-TEMPO was evaluated in terms of survival index, tumour incidence, tumour multiplicity and tumour dielectric parameters. The antioxidant defence status and molecular composition of tumours were assessed. Gap junctions and gap-junctional intercellular communication (GJIC) were studied using ELISA, IHC and Lucifer yellow assay.Results: Mito- EMPO treatment increased survival of animals by 30%, decreased tumour incidence (25%) and tumour multiplicity (39%). The dielectric parameters of tumours in Mito-TEMPO group were indicative of retarded carcinogenesis. Mito-TEMPO administration normalized mean saturation levels in phospholipids and improved glycogen content of the hepatic tissue. Gap junctions and GJIC which were severely impaired in hepatocarcinogenesis, improved after mito-TEMPO treatment.Conclusion: Mito-TEMPO was effective in combating hepatocarcinogenesis

Item Type: Article
Uncontrolled Keywords: Hepatocellular carcinoma; NDEA; Liver cancer; Dielectric spectroscopy
Subjects: Allied Health > MCOAHS Manipal > Nuclear Medicine
Medicine > KMC Manipal > Radiotherapy and Oncology
Depositing User: KMC Library
Date Deposited: 13 Sep 2019 04:28
Last Modified: 13 Sep 2019 04:28
URI: http://eprints.manipal.edu/id/eprint/154456

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