Effects of the antioxidative vitamins A, C and E on liver metastasis and intrametastatic lipid peroxidation in BOP-induced pancreatic cancer in Syrian hamsters

Pancreatology. 2005;5(4-5):403-9. doi: 10.1159/000086541. Epub 2005 Jun 28.

Abstract

Background/aims: Antioxidative vitamins are known to inhibit metastasis. Therefore we evaluated the impact of vitamins A (retinol), C (ascorbic acid) and E (alpha-tocopherol) on liver metastasis in a model of ductal pancreatic adenocarcinoma in hamster.

Methods: One hundred and twenty male Syrian hamsters were randomized into 8 groups (Gr.) (n = 15). Gr. 1-4 were given 0.5 ml normal saline subcutaneously (s.c.) weekly, whereas Gr. 5-8 received 10 mg N-nitrosobis(2-oxopropyl)amine (BOP)/kg body weight s.c. for 3 months for tumor induction. In the 13th week Gr. 2 and 6 were administered retinol, Gr. 3 and 7 received ascorbic acid and Gr. 4 and 8 were given alpha-tocopherol orally. No treatment was performed in Gr. 1 and 5. After 24 weeks animals were sacrificed, pancreas and liver were histologically determined. Activities of glutathione-peroxidase (GSH-Px), superoxide dismutase (SOD) and concentration of thiobarbituric-acid-reactive substances (TBARS) were analyzed in hepatic tissue.

Results: Retinol and alpha-tocopherol decreased the incidence of liver metastases (44.4 vs. 86.7%, p < 0.05). The number and size of liver metastases were significantly reduced by retinol. Activities of GSH-Px and SOD were increased and concentration of TBARS was decreased in NML and LiMe by all vitamins.

Conclusion: Obviously, antioxidative vitamins prevent oxidative stress in hepatocytes. This may be one mechanism decreasing liver metastasis in pancreatic cancer in the present trial.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / therapeutic use
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / secondary
  • Cricetinae
  • Disease Models, Animal
  • Glutathione Peroxidase / metabolism
  • Lipid Peroxidation / drug effects*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • Male
  • Mesocricetus
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / pathology
  • Nitrosamines
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Vitamin A / therapeutic use
  • Vitamin E / therapeutic use

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Nitrosamines
  • Thiobarbituric Acid Reactive Substances
  • Vitamin A
  • Vitamin E
  • nitrosobis(2-oxopropyl)amine
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Ascorbic Acid