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Chemopreventive effect of dieckol against 7,12‐dimethylbenz(a)anthracene induced skin carcinogenesis model by modulatory influence on biochemical and antioxidant biomarkers
Environmental Toxicology ( IF 4.5 ) Pub Date : 2020-12-21 , DOI: 10.1002/tox.23082
Wenming Xiao 1 , Hongyan Liu 1 , Ying Lei 1 , Huawei Gao 1 , Tahani Awad Alahmadi 2 , Haitao Peng 1 , Wei Chen 3
Affiliation  

Skin cancer is the commonly found type, which contributes to 40% of whole cancer incidences worldwide. Dieckol is an active compound occurs in the marine algae with many biological benefits. In this exploration, we intended to investigate the therapeutic potency of dieckol against the 7,12-dimethylbenz(a)anthracene (DMBA)-triggered skin carcinogenesis in mice. The skin cancer was stimulated to the animals via injecting the 25 μg of DMBA in 100 μL of acetone in shaved dorsal portion along with the 30 mg/kg of dieckol supplementation for 25 week. The antioxidant enzymes and phase-I and -II detoxifying enzymes in the test animals were inspected via standard protocols. Pro-inflammatory markers (IL-6, IL-1β, and TNF-α) level was examined via ELISA kits and the expression of inflammatory molecular markers like p-NF-ƙB, IƙBα and p-IƙBα were studied through western blotting. The expression status of pro- and anti-apoptotic proteins (p53, Bax, Bcl-2, caspase-3, caspase-9, COX-2, TGF-β1) was investigated via real-time polymerase chain reaction (RT-PCR). Our results revealed that the 30 mg/kg of dieckol supplementation noticeably regained the body and liver weight and also diminished the tumor incidence in the DMBA-incited animals. Dieckol treatment exhibited an enhanced antioxidants (SOD, CAT, GPx, and GSH) and reduced phase-I enzymes Cyt-p450 and Cyt-b5 in the DMBA-induced animals. Dieckol also diminished the pro-inflammatory modulators like IL-6, IL-1β and TNF-α. Western blotting result evidenced that the dieckol was inhibited the IƙB/NF-ƙB signaling pathway. RT-PCR study proved the enhanced expression of pro-apoptotic protein (p53, Bax, caspase-3 and -9) in the dieckol treated animals. Histological study also confirmed the therapeutic benefits of Dieckol. Altogether with these findings, it was clear that the dieckol has appreciably allayed the DMBA activated skin tumorigenesis in the mice and it could be a promising agent to treat the human skin cancer in future.

中文翻译:

二甲酚通过调节生化和抗氧化生物标志物对 7,12-二甲基苯(a)蒽诱导的皮肤癌发生模型的化学预防作用

皮肤癌是常见的类型,占全球癌症发病率的 40%。Dieckol 是一种存在于海藻中的活性化合物,具有许多生物学益处。在这项探索中,我们打算研究二烯酚对 7,12-二甲基苯(a)蒽 (DMBA) 引发的小鼠皮肤癌的治疗效力。通过在剃须的背部注射 100 μL 丙酮中的 25 μg DMBA 以及 30 mg/kg 的二烯酚补充剂,持续 25 周,从而刺激动物皮肤癌。通过标准方案检查测试动物中的抗氧化酶和 I 相和 II 相解毒酶。通过 ELISA 试剂盒检测促炎标志物(IL-6、IL-1β 和 TNF-α)水平和炎症分子标志物如 p-NF-ƙB、通过蛋白质印迹研究了 IƙBα 和 p-IƙBα。通过实时聚合酶链反应 (RT-PCR) 研究促凋亡和抗凋亡蛋白 (p53、Bax、Bcl-2、caspase-3、caspase-9、COX-2、TGF-β1) 的表达状态. 我们的结果显示,30 mg/kg 的二烯酚补充剂显着恢复了体重和肝脏重量,并且还降低了 DMBA 诱发动物的肿瘤发生率。Dieckol 处理在 DMBA 诱导的动物中表现出增强的抗氧化剂(SOD、CAT、GPx 和 GSH)和减少的 I 相酶 Cyt-p450 和 Cyt-b5。Dieckol 还减少了促炎调节剂,如 IL-6、IL-1β 和 TNF-α。蛋白质印迹结果证明二酚抑制了 IƙB/NF-ƙB 信号通路。RT-PCR 研究证明促凋亡蛋白(p53、Bax、caspase-3 和 -9) 在 dieckol 处理的动物中。组织学研究也证实了 Dieckol 的治疗益处。与这些发现一起,很明显,二烯酚明显减轻了小鼠中 DMBA 激活的皮肤肿瘤发生,并且它可能是未来治疗人类皮肤癌的有希望的药物。
更新日期:2020-12-21
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