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

Sachin Shetty, Rajesh Kumar, Sanjay Bharati

Research output: Contribution to journalArticle

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-TEMPO 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.

Original languageEnglish
Pages (from-to)76-86
Number of pages11
JournalFree Radical Biology and Medicine
Volume136
DOIs
Publication statusPublished - 20-05-2019

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Diethylnitrosamine
Mitochondria
Tumors
Antioxidants
Neoplasms
Gap Junctions
Liver Glycogen
Oxidative stress
TEMPO
Communication
Incidence
Free Radicals
Assays
Organelles
Phospholipids
Animals
Hepatocellular Carcinoma
Carcinogenesis
Oxidative Stress
Tissue

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

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title = "Mito-TEMPO, a mitochondria-targeted antioxidant, prevents N-nitrosodiethylamine-induced hepatocarcinogenesis in mice",
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-TEMPO 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.",
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Mito-TEMPO, a mitochondria-targeted antioxidant, prevents N-nitrosodiethylamine-induced hepatocarcinogenesis in mice. / Shetty, Sachin; Kumar, Rajesh; Bharati, Sanjay.

In: Free Radical Biology and Medicine, Vol. 136, 20.05.2019, p. 76-86.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mito-TEMPO, a mitochondria-targeted antioxidant, prevents N-nitrosodiethylamine-induced hepatocarcinogenesis in mice

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AU - Bharati, Sanjay

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Y1 - 2019/5/20

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AB - 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-TEMPO 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.

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