Methylated chrysin, a dimethoxy flavone, partially suppresses the development of liver preneoplastic lesions induced by N-nitrosodiethylamine in rats

Food Chem Toxicol. 2011 Jan;49(1):173-8. doi: 10.1016/j.fct.2010.10.013. Epub 2010 Oct 16.

Abstract

The modifying effect of chemically modified chrysin on formation of preneoplastic foci induced by N-nitrosodiethylamine (DEN) was investigated in male rats. Male Wistar rats were administered three intraperitoneal injections of DEN (200 mg/kg bodyweight) interspersed by 2 weeks with or without an oral dose of dimethoxy flavone (DMF 100 mg/kg bodyweight), 2 weeks after DEN initiation. The number of GST-Pi positive foci and proliferating cell nuclear antigen (PCNA)-positive cells were significantly suppressed by the administration of DMF. Real-time RT-PCR analysis revealed that DMF treatment increased mRNA expression levels of apoptotic proteins p53 and fas, cell cycle regulatory proteins chek 2, cdkn1a, rad 50, anti-inflammatory protein pparg whereas the mRNA expression levels of bcl-2 and prdx-2 were decreased compared to mRNA levels in DEN-treated group. Therefore, we propose that DMF partially suppresses the formation of preneoplastic lesions in rats following DEN exposure by regulating anti-inflammatory and apoptosis-promoting events and restoring the cellular redox balance altered by DEN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Carcinogens / toxicity*
  • Cell Cycle Proteins / genetics
  • DNA Primers
  • DNA Repair / genetics
  • Diethylnitrosamine / toxicity*
  • Flavonoids / pharmacology*
  • Glutathione Transferase / metabolism
  • Immunohistochemistry
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / prevention & control*
  • Methylation
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / prevention & control*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Carcinogens
  • Cell Cycle Proteins
  • DNA Primers
  • Flavonoids
  • Proliferating Cell Nuclear Antigen
  • chrysin
  • Diethylnitrosamine
  • Glutathione Transferase