Rabbani Zahid N, Batinic-Haberle Ines, Anscher Mitchell S, Huang Jie, Day Brian J, Alexander Elaine, Dewhirst Mark W, Vujaskovic Zeljko
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):573-80. doi: 10.1016/j.ijrobp.2006.09.053.
To determine whether administration of a catalytic antioxidant, Mn(III) tetrakis(N,N'-diethylimidazolium-2-yl) porphyrin, AEOL 10150, with superoxide dismutase (SOD) mimetic properties, reduces the severity of radiation-induced injury to the lung from single-dose irradiation (RT) of 28 Gy.
Rats were randomly divided into four different dose groups (0, 1, 10, and 30 mg/kg/day of AEOL 10150), receiving either short-term (1 week) or long-term (10 weeks) drug administration via osmotic pumps. Rats received single-dose irradiation (RT) of 28 Gy to the right hemithorax. Breathing rates, body weights, blood samples, histopathology, and immunohistochemistry were used to assess lung damage.
There was no significant difference in any of the study endpoints between the irradiated controls and the three groups receiving RT and short-term administration of AEOL 10150. For the long-term administration, functional determinants of lung damage 20 weeks postradiation were significantly worse for RT + phosphate-buffered saline (PBS) and RT + 1 mg/kg/day of AEOL 10150 as compared with the irradiated groups treated with higher doses of AEOL 10150 (10 or 30 mg/kg/day). Lung histology at 20 weeks revealed a significant decrease in structural damage and collagen deposition in rats receiving 10 or 30 mg/kg/day after radiation in comparison to the RT + PBS and 1 mg/kg/day groups. Immunohistochemistry demonstrated a significant reduction in macrophage accumulation, oxidative stress, and hypoxia in rats receiving AEOL 10150 (10 or 30 mg/kg/day) after lung irradiation compared with the RT + PBS and 1 mg/kg/day groups.
The chronic administration of a novel catalytic antioxidant, AEOL 10150, demonstrates a significant protective effect from radiation-induced lung injury. AEOL 10150 has its primary impact on the cascade of events after irradiation, and adding the drug before irradiation and its short-term administration have no significant additional benefits.
确定给予具有超氧化物歧化酶（SOD）模拟特性的催化抗氧化剂四（N，N'-二乙基咪唑 - 2 - 基）卟啉锰（III）（AEOL 10150）是否能减轻28 Gy单次照射（放疗）对肺部造成的辐射损伤的严重程度。
将大鼠随机分为四个不同剂量组（AEOL 10150剂量分别为0、1、10和30 mg/kg/天），通过渗透泵进行短期（1周）或长期（10周）给药。大鼠右半胸接受28 Gy单次照射（放疗）。通过呼吸频率、体重、血液样本、组织病理学和免疫组织化学来评估肺部损伤。
接受放疗的对照组与接受放疗并短期给予AEOL 10150的三组之间，任何研究终点均无显著差异。对于长期给药，与接受较高剂量AEOL 10150（10或30 mg/kg/天）的放疗组相比，放疗加磷酸盐缓冲盐水（PBS）组和放疗加1 mg/kg/天AEOL 10150组在放疗后20周时肺部损伤的功能指标明显更差。20周时的肺部组织学显示，与放疗加PBS组和1 mg/kg/天组相比，接受10或30 mg/kg/天AEOL 10150的大鼠在放疗后结构损伤和胶原蛋白沉积显著减少。免疫组织化学表明，与放疗加PBS组和1 mg/kg/天组相比，肺部照射后接受AEOL 10150（10或30 mg/kg/天）的大鼠巨噬细胞积聚、氧化应激和缺氧显著减少。
新型催化抗氧化剂AEOL 10150的长期给药对辐射诱导的肺损伤具有显著的保护作用。AEOL 10150主要影响放疗后的一系列事件，在放疗前给药及其短期给药没有显著的额外益处。
