Evaluation of the Chemopreventive Activity of Grape Skin Extract Using Medium-term Oral Carcinogenesis Assay Induced by 4-Nitroquinoline 1-Oxide

Anticancer Res. 2019 Jan;39(1):177-182. doi: 10.21873/anticanres.13095.

Abstract

Background/aim: The aim of this study was to evaluate the chemoprotective potential of grape skin extract following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO).

Materials and methods: Male Wistar rats were distributed into four groups (n=5, per group): Control Group: free access to commercial diet and drinking water for 12 weeks; 4NQO Group: received 4NQO diluted in drinking water daily, for 12 weeks; Grape Skin Extract Group: free access to water and received grape skin extract incorporated with diet for 12 weeks; 4NQO + Grape Skin Extract Group: received 4NQO in drinking water daily and grape extract incorporated with diet for 12 weeks.

Results: Animals treated with grape skin extract revealed a significant reduction in epithelial dysplasia. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and ki-67 immunoexpression was reduced in animals treated with grape skin extract. Western blot analysis showed a significant decrease of p-NFκB p50 and MyD88 protein expression in the groups treated with grape skin extract. Copper-zinc superoxide dismutase, manganese superoxide dismutase, and catalase gene expression did not present any statistically significant differences (p>0.05).

Conclusion: Grape skin extract displayed chemopreventive activity in oral carcinogenesis assays as depicted by its antioxidant, anti-proliferative and anti-inflammatory properties.

Keywords: 4-nitroquinoline 1-oxide; Oral cancer; antioxidant activity; proliferation; rat; toll like signaling pathway.

MeSH terms

  • 4-Nitroquinoline-1-oxide / toxicity
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / chemistry
  • Carcinogenesis / drug effects*
  • Catalase / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mouth Neoplasms / chemically induced
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Plant Extracts / administration & dosage*
  • Plant Extracts / chemistry
  • Rats
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1 / genetics
  • Vitis / chemistry*

Substances

  • Antioxidants
  • Plant Extracts
  • 4-Nitroquinoline-1-oxide
  • Catalase
  • Sod1 protein, rat
  • Superoxide Dismutase
  • Superoxide Dismutase-1