title: 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.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Viçosa, Viçosa, MG, Brazil.
authors.forename: Priscila L
authors.initials: PL
authors.lastname: Sequetto
authors.forename: Tânia T
authors.initials: TT
authors.lastname: Oliveira
authors.forename: Italo A C
authors.initials: IA
authors.lastname: Soares
authors.forename: Izabel R S C
authors.initials: IR
authors.lastname: Maldonado
authors.forename: Vanessa J
authors.initials: VJ
authors.lastname: Mello
authors.forename: Virginia R
authors.initials: VR
authors.lastname: Pizziolo
authors.forename: Márcia R
authors.initials: MR
authors.lastname: Almeida
authors.forename: Rômulo D
authors.initials: RD
authors.lastname: Novaes
mesh_terms: D019813:1,2-Dimethylhydrazine; D000818:Animals; D002273:Carcinogens; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
chemical_list: D002273:Carcinogens; D005419:Flavonoids; C043561:chrysin; D019813:1,2-Dimethylhydrazine