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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
Authors:Priscila L. Sequetto  Tânia T. Oliveira  Ítalo A. C. Soares  Izabel R. S. C. Maldonado  Vanessa J. Mello  Virginia R. Pizziolo  Márcia R. Almeida  Rômulo D. Novaes
Affiliation:1. Department of Biochemistry and Molecular Biology, Federal University of Vi?osa, Av. Peter Henry Rolfs, s/no, 35.570-000, Vi?osa, MG, Brazil
2. Department of Veterinary Medicine, Federal University of Vi?osa, Vi?osa, MG, Brazil
3. Department of General Biology, Federal University of Vi?osa, Vi?osa, MG, Brazil
4. Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil
5. Applied Biotechnology Institute (BIOAGRO), Federal University of Vi?osa, Vi?osa, MG, Brazil
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.
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