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3,3'-二硒代二丙酸对全身γ 射线照射小鼠的抗细胞凋亡、抗炎和免疫调节作用。

Anti-apoptotic, anti-inflammatory, and immunomodulatory activities of 3,3'-diselenodipropionic acid in mice exposed to whole body γ-radiation.

机构信息

Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai, India.

出版信息

Arch Toxicol. 2011 Nov;85(11):1395-405. doi: 10.1007/s00204-011-0687-0. Epub 2011 Mar 5.

Abstract

The present study was designed to evaluate the possible protective effects of 3,3'-diselenodipropionic acid (DSePA), a potent radioprotector, against oxidative organ damage induced by whole body γ-irradiation and explore its mechanistic effects. The mice were subjected to whole body γ-irradiation at 5 Gy for the detection of oxidative stress, apoptosis, and proliferation in the intestinal (jejunum) tissue and at 7 Gy for the examination of intestinal inflammation and immune imbalance. Groups of mice received intraperitoneal injections of DSePA (2 mg/kg/day) or vehicle (phosphate-buffered saline) for 5 consecutive days prior to irradiation. The whole body γ-irradiation of mice led to the induction of oxidative stress and apoptosis in the intestinal tissue, and pretreatment with DSePA significantly reduced both these parameters. It was also found to abrogate the radiation-induced intestinal inflammatory response and augment the proliferation of intestinal cells. Additionally, irradiation-induced polarization of Th1/Th2 immune balance toward the Th2-dominant direction and pretreatment with DSePA ameliorated this shift, which may be beneficial for the recovery from radiation injury. In conclusion, pretreatment with DSePA prevented radiation-induced oxidative damage in small intestine and the underlying mechanisms responsible for this could be attributed to inhibition of oxidative stress, apoptosis, and inflammation.

摘要

本研究旨在评估 3,3'-二硒代二丙酸(DSePA)作为一种有效的辐射防护剂,对全身γ射线照射诱导的氧化器官损伤的可能保护作用,并探讨其机制作用。将小鼠进行全身γ射线照射(5Gy),以检测肠道(空肠)组织中的氧化应激、细胞凋亡和增殖;进行 7Gy 的照射,以检测肠道炎症和免疫失衡。将小鼠分为 DSePA(2mg/kg/天)或对照(磷酸盐缓冲盐水)腹腔注射组,连续 5 天预处理,然后进行照射。全身γ射线照射导致肠道组织氧化应激和细胞凋亡,DSePA 预处理显著降低了这两个参数。它还可以消除辐射诱导的肠道炎症反应,并促进肠道细胞的增殖。此外,照射诱导的 Th1/Th2 免疫平衡向 Th2 优势方向的极化,而 DSePA 预处理改善了这种偏移,这可能有利于从辐射损伤中恢复。总之,DSePA 预处理可预防小肠辐射诱导的氧化损伤,其潜在机制可能归因于抑制氧化应激、细胞凋亡和炎症。

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