Ribeiro Flávia Andressa Pidone, de Moura Carolina Foot Gomes, Gollucke Andrea Pitelli Boiago, Ferreira Mônica Siqueira, Catharino Rodrigo Ramos, Aguiar Odair, Spadari Regina Celia, Barbisan Luis Fernando, Ribeiro Daniel Araki
Department of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil.
Department of Pathology, Federal University of Sao Paulo, UNIFESP, SP, Brazil.
Arch Oral Biol. 2014 Aug;59(8):815-21. doi: 10.1016/j.archoralbio.2014.04.013. Epub 2014 Apr 27.
The aim of this study was to evaluate the chemopreventive activity of an apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline-1-oxide (4NQO).
A total of 30 male Wistar rats were distributed into five groups as follows (n=6 per group): Group 1, negative control group (non-treated group); Group 2, received 4NQO during 8 weeks in drinking water and treated with apple extract at 1% by gavage between the first and fourth weeks daily (initiation phase); Group 3, received 4NQO for 8 weeks in drinking water and treated with apple extract by gavage at 1% between the fifth and eighth weeks daily (promotion phase); Group 4, received apple extract at 1% by gavage for 8 consecutive weeks only; and Group 5, received 4NQO for 8 weeks in drinking water daily.
Histopathological analysis revealed decreased hyperplasic lesions in Group 2 when compared with Group 5. Likewise, decreased dysplastic lesions in Group 3 were observed when compared with Group 5. In Groups 2 and 3, decreased COX-2 and TNF-alpha gene expressions were observed when compared with Group 5. Cytochrome c and caspase 3 levels increased in Groups 2 and 3 when compared with Group 5.
In conclusion, our results demonstrate that apple extract suppresses rat tongue carcinogenesis as a result of anti-inflammatory activity and apoptosis through the intrinsic mitochondrial pathway.
本研究旨在评估苹果提取物在4-硝基喹啉-1-氧化物(4NQO)诱导的中期口腔癌发生试验后的化学预防活性。
总共30只雄性Wistar大鼠被分为以下五组(每组n = 6):第1组,阴性对照组(未处理组);第2组,在8周内饮用含4NQO的水,并在第1至4周每天经口灌胃1%苹果提取物(启动阶段);第3组,在8周内饮用含4NQO的水,并在第5至8周每天经口灌胃1%苹果提取物(促进阶段);第4组,仅连续8周每天经口灌胃1%苹果提取物;第5组,每天饮用含4NQO的水8周。
组织病理学分析显示,与第5组相比,第2组的增生性病变减少。同样,与第5组相比,第3组的发育异常病变减少。与第5组相比,第2组和第3组中COX-2和TNF-α基因表达降低。与第5组相比,第2组和第3组中细胞色素c和半胱天冬酶3水平升高。
总之,我们的结果表明,苹果提取物通过内在线粒体途径的抗炎活性和细胞凋亡抑制大鼠舌癌发生。