In radiobiology and radiation oncology fields, the observation of a phenomenon called radiation-induced bystander effect (RIBE) has introduced the prospect of remotely located tissues’ affection. This phenomenon has been broadly developed to involve the concept of RIBE, which are relevant to the radiation-induced response of a distant tissue other than the irradiated one. The current study aimed at investigating each of the RIBE of cranial irradiation on oxidative and inflammatory status in different organs such as liver, kidney, heart, lung, and spleen. Being a vital target of the cholinergic anti-inflammatory response to an inflammatory stimulus, the splenic α-7-nicotinic acetylcholine receptor (α-7nAchR) was evaluated and the hepatic contents of thioredoxin, peroxisome proliferator-activated receptor-alpha and paraoxinase-1 (Trx/PPAR-α/PON) were also assessed as indicators for the liver oxidative stress and inflammatory responses. Being reported to act as antioxidant and anti-inflammatory agents, simvastatin (SV) and/or sildenafil (SD) were investigated for their effects against RIBE on these organs. These objectives were achieved via the biochemical assessments and the histopathological tissues examinations. Five experimental groups, one sham irradiated and four irradiated groups, were exposed to cranial irradiation at dose level of 25 Gy using an experimental irradiator with a Cobalt (Co⁶⁰) source, RIBE, RIBE + SV (20 mg.(kg.bw)^‐1 day^‐1), RIBE + SD (75 mg.(kg.bw)^‐1 day^‐1), and RIBE + SV + SD. Cranial irradiation induced structural, biochemical, and functional dys-regulations in non-targeted organs. RIBE-induced organs’ injuries have been significantly corrected by the administration of SV and/or SD. Our results suggest the possibility of a potentiated interaction between SV and SD in the modulation of the RIBE associated with head and neck radiotherapy.

在放射生物学和放射肿瘤学领域，对一种称为辐射诱导旁观者效应（RIBE）的现象的观察引入了远程组织影响的前景。这一现象已被广泛发展到涉及 RIBE 的概念，它与受辐射组织以外的远处组织的辐射引起的反应有关。目前的研究旨在调查颅脑照射的每种RIBE对肝、肾、心、肺和脾等不同器官氧化和炎症状态的影响。作为对炎症刺激的胆碱能抗炎反应的重要靶标，我们评估了脾脏 α-7-烟碱乙酰胆碱受体 (α-7nAchR)，并评估了硫氧还蛋白、过氧化物酶体增殖物激活受体-α 和对氧酶-1 的肝脏含量(Trx/PPAR-α/PON) 也作为肝脏氧化应激和炎症反应的指标进行评估。据报道，辛伐他汀 (SV) 和/或西地那非 (SD) 可以作为抗氧化剂和抗炎剂，研究它们对这些器官的 RIBE 的影响。这些目标是通过生化评估和组织病理学组织检查来实现的。五个实验组（一个假照射组和四个照射组）使用带有钴 (Co ⁶⁰ ) 源、RIBE、RIBE + SV (20 mg.(kg.bw)) 的实验照射器以 25 Gy 的剂量水平进行颅脑照射^‐1天^‐1 )、RIBE + SD (75 mg.(kg.bw) ^‐1天^‐1 ) 和 RIBE + SV + SD。颅脑照射引起非靶器官的结构、生化和功能失调。 RIBE 引起的器官损伤已通过 SV 和/或 SD 的施用得到显着纠正。我们的结果表明，在与头颈部放疗相关的 RIBE 调节中，SV 和 SD 之间可能存在增强的相互作用。