Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary radioprotection
Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary radioprotection
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DOI：
10.1016/j.freeradbiomed.2007.10.058
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发表时间：
2008-03-15
影响因子：
7.4
通讯作者：
Vujaskovic, Zeljko
中科院分区：
文献类型：
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作者：
Gauter-Fleckenstein, Benjamin;Fleckenstein, Katharina;Vujaskovic, Zeljko
放射治疗（RT）诱导的肺损伤的发展与慢性活性氧和活性氮（ROS/RNS）的产生有关。MnTE-2-PyP5+是SOD的催化Mn卟啉模拟物，已经证明可以通过清除ROS/RNIS来保护肺部免受rt诱导的损伤。本研究的目的是将MnTE-2-pyp（5+）与新引入的类似物MnTnHex-2-pyp（5+）进行比较，由于其亲脂性，MnTnHex-2-pyp（5+）有望成为更有效的放射性保护剂。这项研究表明,费舍尔老鼠被辐照右手半胸(28 Gy)减少肺损伤时用呼吸频率处理每日皮下注射MnTE-2-PYP5 +(3和6毫克/公斤)或MnTnHex-2-PyP5 +(0.3、0.6或1.0毫克/公斤)2周后rt,然而,在16周post-RT,只有MnTE2-PyP5 + 6毫克/公斤的剂量能够改善氧化损伤,阻止激活HIF-1α和鉴定及损害upregulation CA-IX和VEGF。0.3 mg/kg剂量的MnTnHex-2-PyP5+仅对降低rt诱导的tgf - β和CA-IX表达有效。接受MnTnHex-2-PyP5+（0.3和0.6 mg/kg）治疗的动物体重明显下降。MnTnHex-2-PyP5+具有溶解脂质膜的能力。如果剂量为1mg /kg或更高，会引起注射部位局部刺激/坏死。总之，通过呼吸频率和组织病理学评估，这两种化合物都显示出改善肺损伤的能力。然而，6mg /kg的MnTE-2-PyP5+在降低已知在辐射诱导的肺损伤中起重要作用的关键分子因子的表达方面更有效。(c) 2007爱思唯尔公司版权所有。
Development of radiation therapy (RT)-induced lung injury is associated with chronic production of reactive oxygen and nitrogen species (ROS/RNS). MnTE-2-PyP5+ is a catalytic Mn porphyrin mimic of SOD, already shown to protect lungs from RT-induced injury by scavenging ROS/RNIS. The purpose of this study was to compare MnTE-2-pyp(5+) with a newly introduced analogue MnTnHex-2-pyp(5+), which is expected to be a more effective radioprotector due to its lipophilic properties. This study shows that Fischer rats which were irradiated to their right hemithorax (28 Gy) have less pulmonary injury as measured using breathing frequencies when treated with daily subcutaneous injections of MnTE-2-PYP5+ (3 and 6 mg/kg) or MnTnHex-2-PyP5+ (0.3, 0.6, or 1.0 mg/kg) for 2 weeks after RT. However, at 16 weeks post-RT, only MnTE2-PyP5+ at a dose of 6 mg/kg is able to ameliorate oxidative damage, block activation of HIF-1 alpha and TGF-beta and impair upregulation of CA-IX and VEGF. MnTnHex-2-PyP5+ at a dose of 0.3 mg/kg is effective only in reducing RT-induced TGF-beta and CA-IX expression. Significant loss of body weight was observed in animals receiving MnTnHex-2-PyP5+ (0.3 and 0.6 mg/kg). MnTnHex-2-PyP5+ has the ability to dissolve lipid membranes. causing local irritation/necrosis at injection sites if given at doses of I mg/kg or higher. In conclusion, both compounds show an ability to ameliorate lung damage as measured using breathing frequencies and histopathologic evaluation. However, MnTE-2-PyP5+ at 6 mg/kg proved to be more effective in reducing expression of key molecular factors known to play an important role in radiation-induced lung injury. (c) 2007 Elsevier Inc. All rights reserved.