Subcutaneous administration of bovine superoxide dismutase protects lungs from radiation-induced lung injury.
Subcutaneous administration of bovine superoxide dismutase protects lungs from radiation-induced lung injury.
复制标题
DOI：
10.3109/10715762.2015.1066501
复制
发表时间：
2015-10
影响因子：
3.3
通讯作者：
Vujaskovic Z
中科院分区：
文献类型：
--
作者：
Antonic V;Rabbani ZN;Jackson IL;Vujaskovic Z
本研究的目的是确定辐射（RT）暴露后单次给予抗氧化酶牛超氧化物歧化酶（bSOD）是否减轻大鼠肺毒性的发生。将雌性F344大鼠（n=60）分为6个实验组：（1）RT，单剂量21戈伊至右侧胸部;（2）RT+5 mg/kg bSOD;（3）RT+15 mg/kg bSOD;（4）无RT;（5）假RT+5 mg/kg bSOD;和（6）假RT+15 mg/kg bSOD。照射后24小时皮下注射bSOD（5或15 mg/kg）。通过测量体重、呼吸频率和组织病理学变化来评价bSOD对放射性肺损伤的影响。免疫组织化学用于评价氧化应激（8-OHdG+、N 0X 4+、硝基酪氨酸+、4 HNE+细胞）、巨噬细胞活化（ED 1+）和受照射组织中促纤维化TGF-β的表达。辐射导致所有评价参数增加。15 mg/kg bSOD治疗显著降低了所有评估参数的水平，包括放射后6周开始的组织损伤和呼吸频率。用5 mg/kg bSOD处理的动物倾向于抑制辐射诱导的肺损伤，但未达到统计学显著性。单次应用bSOD（15 mg/kg）通过抑制ROS/RNS依赖的组织损伤而减轻放射性肺损伤。
The objective of the present study was to determine whether single administration of the antioxidant enzyme bovine superoxide dismutase (bSOD) after radiation (RT) exposure mitigates development of pulmonary toxicity in rats. Female F344 rats (n=60) were divided among six experimental groups: (1) RT, single dose of 21 Gy to the right hemithorax; (2) RT+5 mg/kg bSOD; (3) RT+15 mg/kg bSOD; (4) No RT; (5) sham RT+5mg/kg bSOD; and (6) sham RT+15mg/kg bSOD. A single subcutaneous injection of bSOD (5 or 15 mg/kg) was administered 24 hours postradiation. The effects of bSOD on radiation-induced lung injury were assessed by measurement of body weight, breathing frequency and histopathological changes. Immunohistochemistry was used to evaluate oxidative stress (8-OHdG+, NOX4+, nitrotyrosine+, 4HNE+ cells), macrophage activation (ED1+), and expression of profibrotic TGF-β in irradiated tissue. Radiation led to an increase in all evaluated parameters. Treatment with 15mg/kg bSOD significantly decreased levels of all evaluated parameters including tissue damage and breathing frequency starting 6 weeks post-radiation. Animals treated with 5 mg/kg bSOD trended toward a suppression of radiation-induced lung damage but did not reach statistical significance. The single application of bSOD (15mg/kg) ameliorates radiation induced lung injury through suppression of ROS/RNS dependent tissue damage.