Acharyya Nirmallya, Sajed Ali Sk, Deb Bimal, Chattopadhyay Sandip, Maiti Smarajit
Department of Biochemistry and Biotechnology, Cell and Molecular Therapeutics Laboratory, Oriental Institute of Science and Technology, Vidyasagar University, Midnapore, 721102, West Bengal, India.
Department of Bio-Medical Laboratory Science and Management (UGC Innovative Department), Vidyasagar University, Midnapore, 721102, West Bengal, India.
Environ Toxicol. 2015 Sep;30(9):1033-44. doi: 10.1002/tox.21977. Epub 2014 Mar 11.
This study elucidates the protective role of Green tea (Camellia sinensis or CS) against arsenic-induced mutagenic DNA-breakage/intestinal (small) damages in female rats. Intestinal epithelial cells receive ingested arsenic initially. Though, the possibility of damages in this tissue is immense and the therapeutic strategies against this damage are of great concern, reports on either issue are scanty. Our earlier study on arsenic-exposed human unveils a link between carcinogenesis and mutagenic DNA damage. Here, we demonstrate that supplementation of CS-extract (10 mg/mL water) with NaAsO2 (0.6 ppm)/100 g b.w. for 28 days to rats offered a significant protection against arsenic-induced oxidative damages to DNA and intestinal (small) tissues by buttressing antioxidant systems. Necrotic and apoptotic damages and their CS-protection are shown in DNA-fragmentation, comet-assay, and histoarchitecture (hematoxylin and eosin and periodic acid-schiff staining) results. Only arsenic exposure significantly decreased intestinal superoxide dismutase, catalase activities, and level of soluble thiol with a concomitant increase in malondialdehyde/conjugated dienes. Alteration of serum necrotic marker lactate dehydrogenase and the metabolic inflammatory marker c-reactive protein also indicate the impairment may be occurring at transcription and/or cellular signal transduction level. In addition, in situ incubation in rat intestinal loop filled for 24 h with NaAsO2 alone (250 µM) or with aqueous CS-extract (250 mg/mL) suggests that small intestinal epithelial cells are significantly protected by CS against arsenic-associated necrotic/mutagenic damages, which is observed in DNA-breakage studies. In conclusion, besides intensifying endogenous antioxidant system, CS polyphenols also offer a direct role on free radical scavenging activity that is associated to the protection from mutagenic DNA-breakages and prevention of tissue necrosis/carcinogenesis generated by arsenic.
本研究阐明了绿茶（茶树或CS）对雌性大鼠砷诱导的致突变性DNA断裂/肠道（小肠）损伤的保护作用。肠道上皮细胞首先接触摄入的砷。然而，该组织受损的可能性极大，针对这种损伤的治疗策略备受关注，但关于这两个问题的报道都很少。我们早期对砷暴露人群的研究揭示了致癌作用与致突变性DNA损伤之间的联系。在此，我们证明，给大鼠补充CS提取物（10 mg/mL水）和NaAsO2（0.6 ppm）/100 g体重，持续28天，通过增强抗氧化系统，可显著保护大鼠免受砷诱导的DNA和肠道（小肠）组织氧化损伤。DNA片段化、彗星试验和组织架构（苏木精和伊红染色以及过碘酸-希夫染色）结果显示了坏死和凋亡损伤以及CS的保护作用。仅砷暴露会显著降低肠道超氧化物歧化酶、过氧化氢酶活性和可溶性硫醇水平，同时丙二醛/共轭二烯水平升高。血清坏死标志物乳酸脱氢酶和代谢炎症标志物c反应蛋白的改变也表明损伤可能发生在转录和/或细胞信号转导水平。此外，在大鼠肠袢中分别用单独的NaAsO2（250 µM）或CS水提取物（250 mg/mL）原位孵育24小时，结果表明小肠上皮细胞受到CS的显著保护，免受砷相关的坏死/致突变损伤，这在DNA断裂研究中得到了观察。总之，除了增强内源性抗氧化系统外，CS多酚还在自由基清除活性方面发挥直接作用，这与保护免受致突变性DNA断裂以及预防砷产生的组织坏死/致癌作用相关。
