Early and late administration of MnTE-2-PyP5+ in mitigation and treatment of radiation-induced lung damage.
Early and late administration of MnTE-2-PyP5+ in mitigation and treatment of radiation-induced lung damage.
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DOI：
10.1016/j.freeradbiomed.2010.01.020
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发表时间：
2010-04-15
影响因子：
7.4
通讯作者：
Vujaskovic, Zeljko
中科院分区：
文献类型：
--
作者：
Gauter-Fleckenstein, Benjamin;Fleckenstein, Katharina;Owzar, Kouros;Jiang, Chen;Reboucas, Julio S.;Batinic-Haberle, Ines;Vujaskovic, Zeljko
放射性肺损伤的一个基本机制是慢性产生活性氧和氮。本研究的目的是确定抗氧化剂和氧化还原调节剂锰卟啉(MnTe-2-PyP5+)减轻和/或治疗IR所致肺损伤的最佳时间。雌性Fischer-344大鼠右侧胸部照射，剂量为28Gy.照射后2、6、12、24、72小时或8周后，皮下注射PBS或MnTE-2-PyP5+(6 mg/kg/24小时)，共2周。IR后10周处死动物。终点：体重、呼吸频率、组织病理学和免疫组织化学(8-OHdG；ED-1；转化生长因子-β；缺氧诱导因子-1α；血管内皮生长因子[A])。通过呼吸频率测量，所有动物都观察到了MnTe-2-PyP5+对功能损伤的显著辐射防护作用。经MnTe-2-PYP5+处理2、6、12 h后，8-OHdG、HIF-1α、转化生长因子-β和血管内皮生长因子(A)的免疫染色显著降低。在完全发展的肺损伤(IR后8周)开始治疗的动物中，观察到低氧诱导因子-1α、转化生长因子-β和血管内皮生长因子(A)的显著减少，以及肺损伤(组织病理学)的总体减轻。催化锰卟啉抗氧化剂和氧化还原信号通路调节剂MnTe-2-PyP5+在IR后12小时内给药可减轻辐射引起的肺损伤。更重要的是，这是第一项证明MnTE-2-PyP5+在IR后8周建立肺损伤时开始可以逆转整体肺损伤的研究。辐射防护作用可能是通过抑制氧化应激和减少关键转录因子以及促血管生成和促纤维化细胞因子的激活来实现的。
Chronic production of reactive oxygen and nitrogen species is an underlying mechanism of radiation (IR)-induced lung injury. The purpose of this study was to determine the optimum time of an antioxidant and redox-modulating Mn porphyrin, MnTE-2-PyP5+, delivery to mitigate and/or treat IR-induced lung damage. Female Fischer-344 rats were irradiated to their right hemithorax (28 Gy). Irradiated animals were treated with PBS or MnTE-2-PyP5+ (6 mg/kg/24h) delivered for 2 weeks by s.c.- implanted osmotic pumps (beginning after 2, 6, 12, 24, 72 hours or 8 weeks). Animals were sacrificed 10 weeks post IR. Endpoints were: body weight, breathing frequency, histopathology, and immunohistochemistry (8-OHdG; ED-1; TGF-β; HIF-1α; VEGF [A]). A significant radioprotective effect on functional injury, measured by breathing frequencies, was observed for all animals treated with MnTE-2-PyP5+. Treatment with MnTE-2-PyP5+ starting 2 h, 6 h, and 12 h but not after 24 h or 72 h resulted in a significant decrease in immunostaining for 8-OHdG, HIF-1α, TGF-β, and VEGF (A). A significant decrease in HIF-1α, TGF-β, and VEGF (A), as well as an overall reduction in lung damage (histopathology) was observed in animals beginning treatment at the time of fully developed lung injury (8 weeks post IR). The catalytic manganese porphyrin antioxidant and modulator of redox-based signalling pathways, MnTE-2-PyP5+, mitigates radiation-induced lung injury when given within the first 12 hours after IR. More importantly, this is the first study to demonstrate MnTE-2-PyP5+ can reverse overall lung damage when started at the time of established lung injury 8 weeks post IR. The radioprotective effects are presumably mediated through both its ability to suppress oxidative stress as well as to decrease activation of key transcription factors and proangiogenic and profibrogenic cytokines.
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影响因子：
7.4
作者：
Gauter-Fleckenstein, Benjamin;Fleckenstein, Katharina;Vujaskovic, Zeljko
通讯作者：
Vujaskovic, Zeljko
影响因子：
5.5
作者：
Agapito, Maria Teresa;Sanz-Alfayate, Gloria;Obeso, Ana
通讯作者：
Obeso, Ana
影响因子：
5.5
作者：
James, PE;Grinberg, OY;Swartz, HM
通讯作者：
Swartz, HM
DOI：
10.1016/j.ijrobp.2006.12.056
发表时间：
2007-05-01
影响因子：
7
作者：
Fleckenstein, Katharina;Zgonjanin, Larisa;Vujaskovic, Zeljko
通讯作者：
Vujaskovic, Zeljko
影响因子：
11.2
作者：
Jaramillo MC;Frye JB;Crapo JD;Briehl MM;Tome ME
通讯作者：
Tome ME