Department of Biochemistry, University of Madras, Maraimalai Campus, Guindy, Chennai, India.
Toxicol Appl Pharmacol. 2012 May 15;261(1):10-21. doi: 10.1016/j.taap.2012.02.004. Epub 2012 Feb 17.
The objective of the present study is to investigate the therapeutic efficacy of baicalein (BE) on inflammatory cytokines, which is in line with tumor invasion factors and antioxidant defensive system during benzo(a)pyrene [B(a)P] (50mg/kg body weight) induced pulmonary carcinogenesis in Swiss albino mice. After experimental period, increased levels of total and differential cell count in bronchoalveolar lavage fluid were observed. Accompanied by marked increase in immature mast cell by toluidine blue staining and mature mast cell by safranin-alcian blue staining in B(a)P-induced lung cancer bearing animals. Protein expression levels studied by immunohistochemistry and immunoblot analysis of cytokines such as tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were also found to be significantly increased in lung cancer bearing animals. B(a)P-exposed mice lung exhibits activated expression of nuclear transcription factor kappa-B as confirmed by immunofluorescence and immunoblot analysis. Administration of BE (12 mg/kg body weight) significantly counteracted all the above deleterious changes. Moreover, assessment of tumor invasion factors on protein levels by immunoblot and mRNA expression levels by RT-PCR revealed that BE treatment effectively negates B(a)P-induced upregulated expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and cyclo-oxygenase-2. Further analysis of lipid peroxidation markers such as thiobarbituric acid reactive substances, hydro-peroxides and antioxidants such as glutathione-S-transferase and reduced glutathione in lung tissue was carried out to substantiate the antioxidant effect of BE. The chemotherapeutic effect observed in the present study is attributed to the potent anti-inflammatory and antioxidant potential by BE against pulmonary carcinogenesis.
本研究旨在探讨白杨素(BE)对炎症细胞因子的治疗效果,这与苯并[a]芘(B(a)P)(50mg/kg 体重)诱导的瑞士白化小鼠肺致癌过程中的肿瘤侵袭因子和抗氧化防御系统相符。实验期间,观察到支气管肺泡灌洗液中的总细胞和分类细胞计数增加。在 B(a)P 诱导的肺癌荷瘤动物中,甲苯胺蓝染色显示不成熟肥大细胞和萨凡纳-阿尔辛蓝染色显示成熟肥大细胞明显增加。免疫组织化学研究的蛋白表达水平以及细胞因子如肿瘤坏死因子-α、白细胞介素-1β和诱导型一氧化氮合酶的免疫印迹分析也发现肺癌荷瘤动物的蛋白表达水平显著增加。免疫荧光和免疫印迹分析证实,B(a)P 暴露的小鼠肺中核转录因子 kappa-B 的表达被激活。BE(12mg/kg 体重)的给药显著抵消了所有上述有害变化。此外,通过免疫印迹和 RT-PCR 评估肿瘤侵袭因子在蛋白水平和 mRNA 表达水平上的变化,发现 BE 治疗有效抑制了 B(a)P 诱导的基质金属蛋白酶-2、基质金属蛋白酶-9 和环氧化酶-2 的上调表达。进一步分析肺组织中的脂质过氧化标志物,如硫代巴比妥酸反应物质、氢过氧化物和抗氧化剂,如谷胱甘肽-S-转移酶和还原型谷胱甘肽,以证实 BE 的抗氧化作用。本研究中观察到的化疗效果归因于 BE 对肺致癌作用的强大抗炎和抗氧化潜力。