Radioprotective Effect of Whey Hydrolysate Peptides against γ-Radiation-Induced Oxidative Stress in BALB/c Mice

Radiation therapy is widely used in the treatment of tumor diseases, but it can also cause serious damage to the body, so it is necessary to find effective nutritional supplements. The main purpose of this study is to evaluate the protective effect of whey hydrolysate peptides (WHPs) against ⁶⁰Coγ radiation damage in mice and explore the mechanism. BALB/c mice were given WHPs by oral gavage administration for 14 days. Then, some mice underwent a 30-day survival test after 8 Gy radiation, and other mice received 3.5 Gy radiation to analyze the changes in body weight, hematology and bone marrow DNA after three and 14 days. In addition, through further analysis of the level of oxidative stress and intestinal barrier function, the possible mechanism of the radioprotective effect of WHPs was explored. The study found WHPs can prolong survival time, restore body weight, and increase the number of peripheral blood white blood cells and bone marrow DNA content in irradiated mice. In addition, WHPs can significantly improve the antioxidant capacity, inhibit pro-inflammatory cytokines and protect the intestinal barrier. These results indicate that WHPs have a certain radioprotective effect in mice, and the main mechanism is related to reducing oxidative damage.     

山莨菪碱对耳蜗辐射防护作用的动物实验研究

目的研究山莨菪碱对耳蜗辐射损伤的防护作用。方法健康豚鼠25只随机分成三组：对照组、单纯放射组和山莨菪碱防护组，每组观察10耳。放疗前30分钟，按每公斤体重20mg于山莨菪碱防护组豚鼠的股部肌肉注射山莨菪碱，对照组和单放组在上述部位注射等量生理盐水。用直线加速器所产生的6Mev电子线对山莨菪碱防护组和单纯放射组豚鼠的耳颞部予以分次照射，总剂量达到60Gy后作耳蜗毛细胞的光镜及扫描电镜观察。结果耳蜗基底膜铺片表明对照组照射耳耳蜗内外毛细胞排列整齐无缺如，单纯放疗组照射耳耳蜗外毛细胞有大量缺如，内毛细胞有少许缺如，山莨菪碱防护组照射耳耳蜗外毛细胞少许缺如，内毛细胞无缺如；扫描电镜表明对照组照射耳耳蜗外毛细胞的纤毛排列整齐无倒伏、缺失，单纯放疗组照射耳耳蜗外毛细胞的纤毛明显倒伏、缺失、排列紊乱，山莨菪碱防护组照射耳耳蜗外毛细胞的纤毛排列基本整齐，偶见倒伏现象。结论①分割剂量60Gy对豚鼠耳颞部照射可造成耳蜗毛细胞损害，②山莨菪碱对耳蜗辐射损伤具有保护作用。     

Radioprotective Effect of Achillea millefolium L Against Genotoxicity Induced by Ionizing Radiation in Human Normal Lymphocytes

The radioprotective effect of Achillea millefolium L (ACM) extract was investigated against genotoxicity induced by ionizing radiation (IR) in human lymphocytes. Peripheral blood samples were collected from human volunteers and incubated with the methanolic extract of ACM at different concentrations (10, 50, 100, and 200 μg/mL) for 2 hours. At each dose point, the whole blood was exposed in vitro to 2.5 Gy of X-ray and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cell. Antioxidant capacity of the extract was determined using free radical-scavenging method. The treatment of lymphocytes with the extract showed a significant decrease in the incidence of micronuclei binucleated cells, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection and decrease in frequency of micronuclei were observed at 200 μg/mL of ACM extract which completely protected genotoxicity induced by IR in human lymphocytes. Achillea millefolium extract exhibited concentration-dependent radical-scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. These data suggest that the methanolic extract of ACM may play an important role in the protection of normal tissues against genetic damage induced by IR.     

乌灵菌发酵液抗辐射功能研究

目的 研究乌灵菌发酵液对小鼠抗辐射功能的影响。方法 通过迟发型超敏反应（delayed type hypersensitivity,DTH）、脾淋巴细胞增殖转化试验、血清溶血素和凝集素水平检测、碳粒廓清试验观察乌灵菌发酵液对免疫功能的影响;通过检测辐射损伤小鼠外周血液学指标、骨髓有核细胞数、骨髓细胞微核率与血清及脏器中的脂质过氧化产物丙二醛（MDA）含量观察乌灵菌发酵液对氧化应激与造血功能的影响。结果 与正常组相比,乌灵菌发酵液3,0.6 g·kg^-1剂量组DTH反应明显增强（P<0.01）,脾淋巴细胞增殖转化功能、血清溶血素、碳粒廓清指数及胸腺系数显著提高（P<0.05或P<0.01）;与模型组相比,给药组骨髓有核细胞数与骨髓细胞微核率无明显差异,血清与心脏MDA含量显著降低（P<0.05或P<0.01）,白细胞数量显著增加（P<0.01）,结论 乌灵菌发酵液可能通过增强机体免疫调节能力与造血功能来发挥抗辐射功效。     

Radioprotective Agents: Strategies and Translational Advances

Radioprotectors are agents required to protect biological system exposed to radiation, either naturally or through radiation leakage, and they protect normal cells from radiation injury in cancer patients undergoing radiotherapy. It is imperative to study radioprotectors and their mechanism of action comprehensively, looking at their potential therapeutic applications. This review intimately chronicles the rich intellectual, pharmacological story of natural and synthetic radioprotectors. A continuous effort is going on by researchers to develop clinically promising radioprotective agents. In this article, for the first time we have discussed the impact of radioprotectors on different signaling pathways in cells, which will create a basis for scientific community working in this area to develop novel molecules with better therapeutic efficacy. The bright future of exceptionally noncytotoxic derivatives of bisbenzimidazoles is also described as radiomodulators. Amifostine, an effective radioprotectant, has been approved by the FDA for limited clinical use. However, due to its adverse side effects, it is not routinely used clinically. Recently, CBLB502 and several analog of a peptide are under clinical trial and showed high success against radiotherapy in cancer. This article reviews the different types of radioprotective agents with emphasis on the strategies for the development of novel radioprotectors for drug development. In addition, direction for future strategies relevant to the development of radioprotectors is also addressed.     

血清胸腺因子对放化疗保护作用的实验研究

目的:观察血清胸腺因子在对抗辐射和抗化疗副作用方面的作用。方法:抗辐射实验:KM小鼠,共6组,除空白组外,其它小鼠接受钴(Co)60照射后,模型组皮下(S.C.)注射0.1 ml生理盐水,FTS低、中、高剂量组分别S.C.注射FTS 0.025、0.25、2.5mg.kg-1,每天一次,连续7 d;阳性药组于实验d 1一次性口服灌胃尼尔雌醇2.5 mg.kg-1,检测免疫活性;对分别接受Co60的600或700拉德辐射小鼠,记录30 d内存活率。抗化疗副作用实验:对肝癌H22细胞的荷瘤小鼠,当日腹腔注射环磷酰胺100mg.kg-1,同时各组给药,每天一次,连续19 d,记录20 d内小鼠存活率。结果:小鼠经辐射后,与模型组比较,FTS各剂量组白细胞总数、对碳粒的吞噬速率和吞噬指数、胸腺系数显著提高(P<0.05);脾脏系数比尼尔雌醇组的脾脏系数略高(P>0.05);对700拉德的辐射小鼠,与模型组比,FTS 0.25 mg.kg-1组30 d内存活率显著增加(P<0.05)、平均存活天数明显延长(P<0.01),与阳性药组一致。荷瘤小鼠接受环磷酰胺化疗,皮下注射FTS给予荷瘤小鼠经化疗后的20 d内存活率增加。结论:血清胸腺因子具有抗辐射、抗化疗副作用,前景广阔。     

辐射对小鼠脾脏损伤及香菇多糖的保护作用

目的 研究辐射对小鼠脾脏的损伤以及香菇多糖对其保护作用。方法 建立小鼠低剂量长期辐射的损伤模型。小鼠随机分为五组,对照组、模型组、香菇多糖组(低、中、高剂量组)。测定各组小鼠的脾脏系数、MTT法测定小鼠脾脏淋巴细胞的增殖情况,法分析脾脏组织的病理变化,用投射电镜法分析脾脏细胞的超微结构。结果：与对照组相比,低剂量慢性辐射能降低小鼠的脾脏系数、抑制脾脏淋巴细胞的增殖,对小鼠脾脏造成病理损伤,破坏脾脏细胞的超微结构。香菇多糖中、高剂量组可明显抑制辐射造成的脾脏的上述损伤。结论：香菇多糖对辐射造成的脾脏损伤具有保护作用。     

Radioprotective activity of glutathione on cognitive ability in X-ray radiated tumor-bearing mice

Objectives: The use of X-ray for therapeutics always raises the problem of radiation hazards to living beings. In this research, we explored the radioprotective activity of glutathione (GSH) on cognitive ability of X-ray radiated tumor-bearing mice.Methods: Forty C57BL/6 mice were chosen to establish the GL261 glioma model and randomly divided into four groups: Model group, X-ray group, Pre-GSH group and Pos-GSH group. Morris water maze test was used to test cognitive ability. Moreover, histopathological observation of hippocampus was observed by hematoxylin and eosin (HE) staining. The protein expression of choline acetyl transferase (ChAT) was measured by western blot, simultaneously the contents of acetylcholinesterase (Ach), superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA),TNF-α and IL-6 were detected by the respective kit.Results: There was a significant difference in X-ray group of the escape latency from the Model group (P<0.05). Besides, HE staining revealed that nucleus in hippocampus cells were pyknotic, glial cells were hyperplastic and the nerve cells were swelling in X-ray group. In X-ray group the expression of ChAT and Ache were decreased versus Model group. Finally, the cognitive ability in Pre-GSH and Pos-GSH group was enhanced than X-ray group, in which the cognitive ability of Pos-GSH group was higher than the Pre-GSH group.Discussion: X-ray impaired the brain tissues and cognitive ability of tumor-bearing mice. The damages of brain tissues were alleviated by Pre-GSH and Pos-GSH protection and the efficacy of Pos-GSH protection was superior to Pre-GSH protection.

Abbreviation Ach: Acetylcholinesterase; GSH: Glutathione; HE: Hematoxylin and eosin; MDA: methane dicarboxylic aldehyde; SOD: Superoxide dismutase; TV: Tumor volume; TW: Tumor weight.     

单味龙血竭对急性放射性肠损伤的防护作用

目的:回顾性分析中药龙血竭预防急性放射性肠损伤的临床疗效。方法:2007年-2013年我院盆腔肿瘤术后放疗患者296例。预防组（157例）给予龙血竭胶囊口服（6～8粒/次,3次/d,与放疗同步）;对照组（139例）给予思密达口服（1包/次,3次/d,与放疗同步）。观察两组急性放射性肠损伤发生的时间、程度,并观察服用龙血竭后的不良反应发生情况。结果:预防组和对照组急性放射性肠损伤发生时间分别为放疗开始第12~30天（平均25天）和第2~35天（平均13天）,预防组发生时间明显晚于对照组。预防组和对照组急性放射性肠损伤总发生率、Ⅱ-Ⅳ级急性放射性肠损伤发生率分别为14.65%、32.37%和5.10%、15.83%,统计学分析均具有显著性差异（χ2=13.09,χ2=9.32,P＜0.01）。两组均未出现严重急性放射性肠损伤（Ⅳ级）。结论:龙血竭防治急性放射性肠损伤发生时间晚、发生率低、程度轻,临床预防效果满意。     

Radioprotective activity of curcumin-encapsulated liposomes against genotoxicity caused by Gamma Cobalt-60 irradiation in human blood cells

Purpose: While the radioprotective activity of curcumin against genotoxicity has been well established, its poor oral bioavailability has limited its successful clinical applications. Nanoscale formulations, including liposomes, have been demonstrated to improve curcumin bioavailability. The objective of the present work was (1) to prepare and characterize curcumin-encapsulated liposomes (i.e. size, colloidal stability, encapsulation efficiency, and payload), and (2) subsequently to evaluate their radioprotective activity against genotoxicity in human blood cells caused by Gamma Cobalt-60 irradiation.

Materials and methods: The curcumin-encapsulated liposomes were prepared by lipid-film hydration method using commercial phosphatidylcholine (i.e. Phospholipon^® 90G). The blood cells were obtained from healthy male donors (n?=?3) under an approved ethics protocol. The cell uptake and the radioprotective activity of the curcumin-encapsulated liposomes were characterized by fluorescence microscopy and micronucleus assay, respectively.

Results: Nanoscale curcumin-encapsulated liposomes exhibiting good physical characteristics and successful uptake by the human blood cells were successfully prepared. The radioprotective activity of the curcumin-encapsulated liposomes was found to be dependent on the curcumin concentration, where an optimal concentration existed (i.e. 30?μg/mL) independent of the irradiation dose, above which the radioprotective activity had become stagnant (i.e. no more reduction in the micronuclei frequency).

Conclusions: The present results established for the first time the radioprotective activity of curcumin-encapsulated liposomes in human blood cells, which coupled by its well-established bioavailability, boded well for its potential application as a nanoscale delivery system of other radioprotective phytochemicals.