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自噬诱导药物卡马西平是一种辐射防护剂和缓解剂。

The autophagy-inducing drug carbamazepine is a radiation protector and mitigator.

机构信息

Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.

出版信息

Int J Radiat Biol. 2011 Oct;87(10):1052-60. doi: 10.3109/09553002.2011.587860. Epub 2011 Jul 5.

DOI:10.3109/09553002.2011.587860
PMID:21728759
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3772684/
Abstract

PURPOSE

To determine whether Carbamazepine (CBZ) is a radiation protector and/or mitigator.

MATERIALS AND METHODS

Murine hematopoietic progenitor 32D cl 3 cells were incubated in 1, 10, or 100 μM CBZ 1 h before or immediately after 0-8 Gy irradiation and assayed for clonogenic survival. Autophagy was assayed by immunoblot for microtubule-associated protein light chain 3 (LC3). In vivo radioprotection and mitigation were determined with C57BL/6NTac mice.

RESULTS

CBZ treatment at 1, 10 or 100 μM for 1 h prior to irradiation increased radioresistance (the dose for 37% survival or D(0)) from control 1.5 ± 0.1 Gy to 2.1 ± 0.2 Gy (P = 0.012), 2.3 ± 0.1 Gy (P = 0.010), and 3.6 ± 0.7 Gy (P = 0.003), respectively; after irradiation increased the extrapolation number (ñ) from 1.5 ± 0.3 to 10.1 ± 4.2 (P = 0.011), 5.5 ± 1.7 (P = 0.019), and 3.6 ± 0.8 (P = 0.014), respectively, and increased autophagy. CBZ treated mice 10 min or 24 h before or 10 min or 12 h after 9.25 Gy total body irradiation (TBI) showed increased survival (P = 0.012, 0.011, 0.0002, and 0.017, respectively).

CONCLUSION

CBZ may be a useful radiation protector and mitigator.

摘要

目的

确定卡马西平(CBZ)是否为辐射防护剂和/或缓解剂。

材料和方法

在 0-8Gy 照射前 1 小时或照射后立即,将 32D cl 3 细胞在 1、10 或 100μM 的 CBZ 中孵育,并检测集落形成细胞的存活情况。通过免疫印迹法检测微管相关蛋白轻链 3(LC3)来检测自噬。使用 C57BL/6NTac 小鼠进行体内辐射防护和缓解作用。

结果

照射前 1、10 或 100μM 的 CBZ 处理 1 小时可提高放射抗性(37%存活剂量或 D(0)),从对照 1.5±0.1Gy 增加到 2.1±0.2Gy(P=0.012)、2.3±0.1Gy(P=0.010)和 3.6±0.7Gy(P=0.003);照射后,将外推数(ñ)从 1.5±0.3 增加到 10.1±4.2(P=0.011)、5.5±1.7(P=0.019)和 3.6±0.8(P=0.014),并增加自噬。在 9.25Gy 全身照射(TBI)前 10 分钟或 24 小时、照射后 10 分钟或 12 小时给予 CBZ 的小鼠显示出存活率增加(P=0.012、0.011、0.0002 和 0.017)。

结论

CBZ 可能是一种有用的辐射防护剂和缓解剂。

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