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萘普生诱导和幽门螺杆菌感染 Wistar 大鼠模型中有机硒化合物的抗菌和溃疡愈合作用。

Antibacterial and ulcer healing effects of organoselenium compounds in naproxen induced and Helicobacter pylori infected Wistar rat model.

机构信息

Department of Physiology, Deccan College of Medical Sciences, Hyderabad, India.

出版信息

J Trace Elem Med Biol. 2010 Oct;24(4):263-70. doi: 10.1016/j.jtemb.2010.04.003. Epub 2010 Aug 3.

Abstract

Aim of the present study was to evaluate in vitro toxicity and in vivo antibacterial, anti-inflammatory, antiulcer, and antioxidant activities of two organoselenium compounds, selenocystine (SeCys) and ebselen (Ebs). The study was conducted in experimentally induced ulcers in rodent model infected with Helicobacter pylori (H. pylori). In vitro toxicological studies on normal splenic lymphocytes revealed that SeCys and Ebs were non-toxic to the cells even at 100 μM concentration. Antibacterial activity was observed at 500 μg/mL concentration of either of the compounds against H. pylori. In vivo studies after treatment with SeCys and Ebs (500 μg/kg/day) resulted in significant reduction in ROS production and inhibition of lipid peroxidation in gastric tissue. The antioxidant and anti-inflammatory activities of both the compounds were also confirmed by their ability to lower GSH reduction, to induce the expression of antioxidant genes such as GPx-4, and MnSOD and to suppress inflammatory genes namely COX-2, TNF-α and TGF-β. In addition, the immunomodulatory activity of both the compounds was evident by enhance of the CD4 levels and maintenance of the IgG, IL-6 and IL-10 levels. Persistent treatment (500 μg/kg, for 28 days) with both the compounds showed considerable (p<0.05) ulcer healing property supporting its role in gastro protection. In conclusion, the results of our study suggest that both SeCys and Ebs possess broad spectrum of activities without any potential toxicity.

摘要

本研究旨在评估两种有机硒化合物——硒代半胱氨酸(SeCys)和依布硒啉(Ebselen)的体外毒性以及体内的抗菌、抗炎、抗溃疡和抗氧化活性。该研究在感染幽门螺杆菌(H. pylori)的啮齿动物模型中进行了实验性溃疡。体外毒理学研究表明,即使在 100 μM 浓度下,SeCys 和 Ebs 对正常脾淋巴细胞也没有毒性。两种化合物在 500 μg/mL 浓度下均显示出对 H. pylori 的抗菌活性。用 SeCys 和 Ebs(500 μg/kg/天)治疗后的体内研究表明,两种化合物均可显著降低胃组织中 ROS 的产生和脂质过氧化。通过降低 GSH 还原、诱导抗氧化基因如 GPx-4 和 MnSOD 的表达以及抑制炎症基因如 COX-2、TNF-α 和 TGF-β,两种化合物的抗氧化和抗炎活性也得到了证实。此外,两种化合物的免疫调节活性表现为 CD4 水平的提高和 IgG、IL-6 和 IL-10 水平的维持。两种化合物的持续治疗(500 μg/kg,28 天)显示出相当大的(p<0.05)溃疡愈合作用,支持其在胃保护中的作用。总之,我们的研究结果表明,SeCys 和 Ebs 都具有广泛的活性而没有任何潜在的毒性。

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