The flavonoid chrysin attenuates colorectal pathological remodeling reducing the number and severity of pre-neoplastic lesions in rats exposed to the carcinogen 1,2-dimethylhydrazine

Cell Tissue Res. 2013 May;352(2):327-39. doi: 10.1007/s00441-013-1562-5. Epub 2013 Mar 7.

Abstract

Phenolic compounds are naturally occurring, bioactive substances with marked antioxidant and anti-inflammatory potential. The flavonoid chrysin, found in high levels in honey bee propolis, inhibits the activity of enzymes involved in carcinogenesis. We have investigated the effect of chrysin on pre-neoplastic colorectal lesions (ACF, aberrant crypt foci) in a rat model of chemical carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Female Wistar rats weighing 137.2 ± 24.3 g received weekly one subcutaneous injection of DMH (20 mg/kg) for 10 weeks. The animals were divided into five groups each with seven animals: Group 1, 0.9% saline; Group 2, DMH+0.9% saline; Group 3, DMH+chrysin (10 mg/kg); Group 4, DMH+chrysin (100 mg/kg); Group 5, DMH+chrysin (200 mg/kg). Groups 2 and 3 showed a significant increase in ACF number, nucleolus organizer regions per enterocyte nucleus and nitrite/nitrate serum levels compared with Group 1. Groups 4 and 5 presented a significant reduction in all these parameters compared with Group 2. The levels of antioxidant minerals (copper, magnesium, selenium, zinc) and the number of enteroendocrine and mucin-producing cells were significantly reduced in Groups 2 and 3 but were similar in Groups 4 and 5 compared with Group 1. Chrysin, at 100 mg/kg and 200 mg/kg, was effective in attenuating pathological colorectal remodeling, reducing the number of pre-neoplastic lesions in rats exposed to DMH. Some of these effects might be attributable to the recovery of antioxidant mineral levels, a reduction in systemic nitrosative stress and an inhibition of the cellular proliferation induced by this flavonoid.

MeSH terms

  • 1,2-Dimethylhydrazine
  • Animals
  • Carcinogens
  • Colon / drug effects*
  • Colon / enzymology
  • Colon / pathology
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / prevention & control*
  • Female
  • Flavonoids / pharmacology*
  • Precancerous Conditions / chemically induced*
  • Precancerous Conditions / drug therapy*
  • Precancerous Conditions / pathology
  • Rats
  • Rats, Wistar
  • Rectum / drug effects*
  • Rectum / enzymology
  • Rectum / pathology

Substances

  • Carcinogens
  • Flavonoids
  • chrysin
  • 1,2-Dimethylhydrazine