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Quercetin attenuated oxidative DNA damage through NRF2 signaling pathway in rats with DMH induced colon carcinogenesis.
Life Sciences ( IF 5.2 ) Pub Date : 2020-03-24 , DOI: 10.1016/j.lfs.2020.117584
Saber Ghazizadeh Darband 1 , Shirin Sadighparvar 2 , Bahman Yousefi 3 , Mojtaba Kaviani 4 , Firouz Ghaderi-Pakdel 2 , Ainaz Mihanfar 5 , Yaghoub Rahimi 6 , Kazhal Mobaraki 7 , Maryam Majidinia 7
Affiliation  

Accumulating recent studies have demonstrated the preventive and therapeutic effects of polyphonic compounds such as quercetin in colorectal cancer. Therefore, we aimed to evaluate the underlying mechanisms for positive effects of quercetin in rats with 1,2-dimethylhydrazine (DMH)- induced colorectal cancer. For this purpose, male Wistar rats were classified as 6 groups, including group 1 without any intervention, group 2 as quercetin received rats (50 mg/kg), groups 3 as DMH received rats (20 mg/kg) group 4–6 DMH and quercetin received rats. DNA damage, DNA repair, the expression levels and activities of enzymic antioxidants, non-enzymic antioxidants, and NRF2/Keap1 signaling were evaluated in colon tissues of all groups. Our results showed significant suppression of DNA damage and induction of DNA repair in DMH + Quercetin groups, particularly in entire-period in comparison to other groups (p < .05). The expression levels and activities of enzymic and non-enzymic antioxidants were increased in DMH + Quercetin groups (p < .05). Lipid and protein peroxidation were significantly suppressed in DMH + Quercetin groups (p < .05). In addition, quercetin also modulated NRF2/Keap1 signaling and its targets, detoxifying enzymes in DMH + Quercetin groups. Our finding demonstrated that quercetin supplementation effectively reversed DMH-mediated oxidative stress and DNA damage through targeting NRF2/Keap1 signaling pathway.



中文翻译:

槲皮素通过NRF2信号通路减轻DMH诱导的结肠癌发生大鼠的氧化性DNA损伤。

越来越多的最新研究表明,诸如槲皮素等复音化合物在结直肠癌中具有预防和治疗作用。因此,我们旨在评估槲皮素在1,2-二甲基肼(DMH)诱导的大肠癌大鼠中产生积极作用的潜在机制。为此,将雄性Wistar大鼠分为6组,包括第1组,不进行任何干预,第2组为接受槲皮素的大鼠(50 mg / kg),第3组为DMH的大鼠(20 mg / kg),第4-6组DMH槲皮素收到了老鼠。在所有组的结肠组织中评估了DNA损伤,DNA修复,酶抗氧化剂,非酶抗氧化剂的表达水平和活性以及NRF2 / Keap1信号传导。我们的结果表明,DMH +槲皮素组可显着抑制DNA损伤并诱导DNA修复,p  <.05)。DMH +槲皮素组的酶和非酶抗氧化剂的表达水平和活性均升高(p  <.05)。DMH +槲皮素组的脂质和蛋白质过氧化作用被显着抑制(p <.05)。此外,槲皮素还调节NRF2 / Keap1信号及其靶标,使DMH +槲皮素组中的酶解毒。我们的发现表明,槲皮素补充剂可通过靶向NRF2 / Keap1信号通路有效逆转DMH介导的氧化应激和DNA损伤。

更新日期:2020-03-24
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