National Centre of Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
National Centre for Nuclear Safety and Radiation Control, Atomic Energy Authority, Cairo, Egypt.
Int J Radiat Biol. 2021;97(5):632-641. doi: 10.1080/09553002.2021.1893856. Epub 2021 Mar 15.
Cyclophosphamide (Cyp) is one of the most commonly used, wide spectrum chemotherapeutic agents. Cyp has multi-organ toxicities that are dose limiting, thus it's mostly used in chemotherapeutic combinations. Radiation is well known as a hazardous sort of energy, recent studies are interested in studying the beneficial therapeutic effects of low-dose gamma radiation. This study examined the protective effect of two different doses/dose-rates of irradiation either alone or combined with telmisartan against Cyp-induced cardiotoxicity.
Rats were divided into seven groups; (1): Control, (2): Cyp, (3-4): 0.05 Gy low dose rate (LDR) irradiation, 0.25 Gy high dose rate (HDR) irradiation, respectively, prior to Cyp dose, (5-7): telmisartan either alone or with 0.05 Gy LDR-irradiation or 0.25 Gy HDR-irradiation, respectively, prior to Cyp dose. The current investigation studied the effect of Cyp alone or combined with different treatment regimens on serum cTn-I and LDH, nuclear factor-κB (NF-κB) pathway (p65/IκB/IKK-α/IKK-ß) in the myocardium. Pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were assessed in addition to histopathological examination of the heart.
Low-dose irradiation attenuated cardiac enzymes, pro-inflammatory cytokines, NF-κB content, and histology, in both low and HDRs. Furthermore, the combination of low-dose irradiation with telmisartan (an angiotensin-II receptor type-1 blocker and a known cardio-protective drug) offered the best histological results.
Low-dose irradiation-induced amelioration is partially but not completely through canonical activation of NF-κB, and may have another atypical pathway. While telmisartan probably ameliorates NF-κB totally through canonical pathway.
环磷酰胺（Cyp）是最常用的广谱化疗药物之一。Cyp 具有多种器官毒性，剂量限制，因此主要用于化疗联合治疗。辐射是众所周知的危险能量，最近的研究有兴趣研究低剂量伽马辐射的有益治疗效果。本研究检查了两种不同剂量/剂量率的单独或联合替米沙坦照射对 Cyp 诱导的心脏毒性的保护作用。
大鼠分为七组；（1）：对照组，（2）：Cyp 组，（3-4）：分别在 Cyp 剂量前接受 0.05Gy 低剂量率（LDR）照射、0.25Gy 高剂量率（HDR）照射，（5-7）：替米沙坦分别单独或与 0.05Gy LDR 照射或 0.25Gy HDR 照射联合使用，分别在 Cyp 剂量前使用。本研究探讨了 Cyp 单独或联合不同治疗方案对血清 cTn-I 和 LDH、心肌核因子-κB（NF-κB）途径（p65/IκB/IKK-α/IKK-ß）的影响。还评估了促炎细胞因子 IL-1β、IL-6 和 TNF-α以及心脏的组织病理学检查。
低剂量照射可减轻低剂量和高剂量的心脏酶、促炎细胞因子、NF-κB 含量和组织病理学变化。此外，低剂量照射与替米沙坦（血管紧张素 II 受体 1 阻滞剂和已知的心脏保护药物）联合使用可获得最佳的组织学结果。
低剂量照射诱导的改善部分但不完全通过经典激活 NF-κB，可能存在另一种非典型途径。而替米沙坦可能通过经典途径完全改善 NF-κB。
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