Naringenin (4,5,7-trihydroxyflavanone) suppresses the development of precancerous lesions via controlling hyperproliferation and inflammation in the colon of Wistar rats

Environ Toxicol. 2018 Apr;33(4):422-435. doi: 10.1002/tox.22528. Epub 2018 Jan 18.

Abstract

Colon cancer is a world-wide health problem and one of the most dangerous type of cancer, affecting both men and women. Naringenin (4, 5, 7-trihydroxyflavanone) is one of the major flavone glycoside present in citrus fruits. Naringenin has long been used in Chinese's traditional medicine because of its exceptional pharmacological properties and non-toxic nature. In the present study, we investigated the chemopreventive potential of Naringenin against 1,2-dimethyhydrazine (DMH)-induced precancerous lesions, that is, aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the oxidative stress, inflammation and hyperproliferation, in the colon of Wistar rats. Animals were divided into five groups. In groups 3-5, Naringenin was administered at the dose of 50 mg/kg b. wt. orally while in groups 2-4, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b. wt. once a week for first 5 weeks and animals were euthanized after 10 weeks. Administration of Naringenin ameliorated the development of DMH-induced lipid peroxidation, ROS formation, precancerous lesions (ACF and MDF) and it also reduced the infiltration of mast cells, suppressed the immunostaining of NF-κB-p65, COX-2, i-NOS PCNA and Ki 67 Naringenin treatment significantly attenuated the level of TNF-α and it also prevented the depletion of the mucous layer. Our findings suggest that Naringenin has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of Naringenin.

Keywords: Naringenin; chemoprevention; colon toxicity; environmental toxicant.

MeSH terms

  • Aberrant Crypt Foci / pathology
  • Aberrant Crypt Foci / prevention & control
  • Animals
  • Anticarcinogenic Agents / therapeutic use*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control*
  • Flavanones / therapeutic use*
  • Inflammation / metabolism
  • Inflammation / prevention & control
  • Lipid Peroxidation
  • Male
  • Mucins / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Precancerous Conditions / prevention & control*
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anticarcinogenic Agents
  • Flavanones
  • Mucins
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • naringenin