6-Shogaol通过调节PRDX1相关的氧化应激、炎症和增殖,预防苯并[A]芘暴露引起的肺癌发生,该实验采用了小鼠模型。
6-Shogaol prevents benzo (A) pyrene-exposed lung carcinogenesis via modulating PRDX1-associated oxidative stress, inflammation, and proliferation in mouse models.
发表日期:2023 Aug 28
作者:
Shuang Pan, Yaming Li, Jinzhao Zhang
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
在这项研究中,我们调查了6-姜酚酸(6-SGL)通过调节PRDX1相关的氧化应激、炎症和增殖,在苏白小鼠模型的苯并芘(BaP)暴露性肺癌发生中的化学预防作用。小鼠口服BaP(50 mg/kg 体重)每周两次,连续四周,维持16 周。在BaP暴露前1小时,口服给予小鼠6-SGL(30 mg/kg 体重),维持16 周。实验结束后,6-SGL(30 mg/kg 体重)防止了小鼠体重的减少,增加了肺重量和肿瘤总数。此外,我们观察到6-SGL减轻了BaP诱导的小鼠脂质过氧化和抗氧化物质的活性。此外,6-SGL阻止了BaP暴露小鼠中MAPK家族蛋白的磷酸化,如Erk1、p38和Jnk1。PRDX1是一种重要的抗氧化蛋白,清除有毒自由基,并增强几种抗氧化蛋白。PRDX1的过表达显著抑制MAPK、增殖和炎症信号轴。因此,PRDX1被认为是预防BaP诱导的肺癌的新型靶蛋白。在这项研究中,我们得到了6-SGL处理在小鼠模型中可逆转BaP诱导的PRDX1表达耗竭。此外,6-SGL预处理(30 mg/kg 体重)显著抑制了BaP暴露小鼠中促炎细胞因子(TNF-α、IL-6、IL-β1、IL-10)和增殖标志物(Cyclin-D1、Cyclin-D2和PCNA)的增强。组织病理学研究也证实了6-SGL有效保护细胞减少损伤。因此,该研究证明了6-SGL在增强PRDX1表达方面可能是一种潜在的植物化学物质,可作为BaP引起的肺癌的化学预防剂。© 2023 Wiley Periodicals LLC.
In this study, we have investigated the chemopreventive role of 6-shogaol (6-SGL) on benzopyrene (BaP) exposed lung carcinogenesis by modulating PRDX1-associated oxidative stress, inflammation, and proliferation in Swiss albino mouse models. Mice were exposed to BaP (50 mg/kg b.wt) orally twice a week for four consecutive weeks and maintained for 16 weeks, respectively. 6-SGL (30 mg/kg b.wt) were orally administered to mouse 1 h before BaP exposure for 16 weeks. After the experiment's termination, 6-SGL (30 mg/kg b.wt) prevented the loss in body weight, increased lung weight, and the total number of tumors in the mice. Moreover, we observed that 6-SGL treatment reverted the activity of BaP-induced lipid peroxidation and antioxidants in mice. Also, 6-SGL impeded the phosphorylation of MAPK family proteins such as Erk1, p38, and Jnk1 in BaP-exposed mice. PRDX1 is an essential antioxidant protein that scavenges toxic radicals and enhances several antioxidant proteins. Overexpression of PRDX1 substantially inhibits MAPKs, proliferation, and inflammation signaling axis. Hence, PRDX1 is thought to be a novel targeting protein for preventing BaP-induced lung cancer. In this study, we have obtained the 6-SGL treatment in a mouse model that reverted BaP-induced depletion of PRDX1 expression. Moreover, pretreatment of 6-SGL (30 mg/kg b.wt) significantly inhibited enhanced proinflammatory cytokines (TNF-α, IL-6, IL-β1, IL-10) and proliferative markers (Cyclin-D1, Cyclin-D2, and PCNA) in BaP-exposed mice. The histopathological studies also confirmed that 6-SGL effectively protected the cells with less damage. Thus, the study demonstrated that 6-SGL could be a potential phytochemical and act as a chemopreventive agent in BaP-induced lung cancer by enhancing PRDX1 expression.© 2023 Wiley Periodicals LLC.