Ascorbic acid monoglucoside as antioxidant and radioprotector

Ascorbic acid monoglucoside (AsAG), a glucoside derivative of ascorbic acid, has been examined for its antioxidant and radioprotective abilities. AsAG neutralized 1, 1 diphenyl -2-picryl-hydrazyl (DPPH), a stable free radical in a concentration dependent manner thus indicating its antioxidant ability. AsAG protected mice liver tissues in vitro from peroxidative damage in lipids (measured as TBARS) resulting from 25Gy gamma irradiation. It also protected plasmid pBR322 DNA from gamma-radiation induced strand breaks as evidenced from studies on agarose gel electrophoresis of the plasmid DNA after radiation exposure. Oral administration of AsAG to mice prior to whole body gamma radiation exposure (4Gy) resulted in a reduction of radiation induced lipid peroxides in the liver tissue indicating in vivo radiation protection of membranes. Pulse radiolysis studies indicated that AsAG offered radioprotection by scavenging free radicals. The rate constants for the reactions OH and N(3) radicals with AsAG were determined to be 6.4 x 10(9) dm(3) mol(-1) s(-1) and 2.3 x 10(9) dm(3) mol(-1) s(-1), respectively at pH 7. It was observed that AsAG radicals undergo conjugation as the pH of the solution is raised to 11 in the case of a one-electron oxidation reaction. As the OH(*) radical adds to the ring, the conjugation effect starts appearing at pH 10.     

Caffeine protects mice against whole-body lethal dose of gamma-irradiation.

Administration of caffeine (1,3,7-trimethylxanthine), a major component of coffee, to Swiss mice at doses of 80 or 100 mg/kg body weight 60 min prior to whole-body lethal dose of gamma-irradiation (7.5 Gy) resulted in the survival of 70 and 63% of animals, respectively, at the above doses in contrast to absolutely no survivors (LD-100/25 days) in the group exposed to radiation alone. Pre-treatment with a lower concentration of caffeine (50 mg/kg) did not confer any radioprotection. The protection exerted by caffeine (80 mg/kg), however, was reduced from 70 to 50% if administered 30 min prior to irradiation. The trend statistics reveal that a dose of 80 mg/kg administered 60 min before whole-body exposure to 7.5 Gy is optimal for maximal radioprotection. However, caffeine (80 mg/kg) administered within 3 min after irradiation offered no protection. While there is documentation in the literature that caffeine is an antioxidant and radioprotector against the oxic pathway of radiation damage in a wide range of cells and organisms, this is the first report demonstrating unequivocally its potent radioprotective action in terms of survival of lethally whole-body irradiated mice.     

Radiation protection by diethyldithiocarbamate: protection of membrane and DNA in vitro and in vivo against gamma-radiation

Diethyldithiocarbamate (DDTC) is studied for its antioxidant and radioprotective abilities. DDTC at a concentration of 0.5 mM reduced DPPH radical. DDTC reduced the damage to deoxyribose resulting from hydroxyl radicals generated by Fenton reaction, indicating that the radioprotective abilities of this compound could be due to the free radical scavenging. DDTC protected rat liver microsomal membranes in vitro from peroxidative damage in lipids (measured as TBARS) resulting from 50 Gy gamma-radiation. It also protected plasmid pBR322 DNA from radiation-induced strand breaks. An oral administration of DDTC to mice before whole body gamma-radiation exposure (4 Gy) resulted in a reduction of radiation-induced lipid peroxides in the liver homogenates. An administration of DDTC to mice before gamma-radiation reduced the radiation-induced DNA damage as studied by single cell gel-electrophoresis (comet assay). The comet parameters such as tail length, tail moment, and percent of DNA in tail were found to increase in the blood leukocytes of mice exposed to 4 Gy gamma-radiation. When DDTC was administered to mice before the radiation exposure, the increase in the comet parameters as a result of radiation was prevented, indicating a protection of cellular DNA. The present study has implication for the potential use of DDTC as a radioprotector.     

黄蘑多糖的辐射防护作用及其机理的初步探讨

本文研究了黄蘑多糖的辐射防护作用及其对受照小鼠肝脏组织中LPO含量及SOD、GSH-PX和CAT活性的影响。结果表明,黄蘑多糖可明显提高受致死剂量照射小鼠的30 d存活率(P <0.05),延长存活天数,保护指数可达1.32,并且,黄蘑多糖的这种辐射防护效果与有效的辐射防护药物人参多糖相似。进一步研究发现,小鼠经8.0Gy X射线照射后72h,黄蘑多糖能明显降低受照小鼠肝脏中LPO含量(P <0.01),且显著增强其SOD、GSH-PX和CAT活性(P <0.05)。提示,黄蘑多糖具有明显的辐射防护作用,且可与人参多糖相比。其作用机理与促进自由基清除,抑制或阻断自由基引发的脂质过氧化反应,提高机体抗氧化能力有关。     

Eugenol as an in vivo radioprotective agent

In the present work, an attempt has been made to evaluate the possible in vivo radioprotection by eugenol. Swiss albino mice were administered different doses of eugenol (75,150 and 300 mg/kg) before exposure to 1.5 Gy of gamma radiation. The micronucleus test was carried out to determine the genetic damage in bone marrow. Our results demonstrated significant reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) with all three eugenol doses. Eugenol (150 mg/kg) was also tested against different doses of radiation (0.5, 1, 1.5, and 2 Gy) and was found to afford significant radioprotection. Reduction in the incidence of MnPCEs could be noticed up to 72 h postirradiation (1.5 Gy). Moreover, the level of peroxidative damage and the specific activities of lactate dehydrogenase (LDH) and methylglyoxalase I (Gly I) were observed in the liver of mice treated with eugenol for seven days in comparison to untreated mice. The results revealed that eugenol exerted significant protection against oxidative stress. This possibility was further supported by the enhanced response of Gly I and the lowered activity of LDH. The present findings suggested that eugenol has a radioprotective potential.     

Free radical scavenger edaravone suppresses x-ray-induced apoptosis through p53 inhibition in MOLT-4 cells

Edaravone, a clinical drug used widely for the treatment of acute cerebral infarction, is reported to scavenge free radicals. In the present study, we investigated the radioprotective effect of edaravone on X-ray-induced apoptosis in MOLT-4 cells. Apoptosis was determined by the dye exclusion test, Annexin V binding assay, cleavage of caspase, and DNA fragmentation. We found that edaravone significantly suppressed the X-ray-induced apoptosis. The amount of intracellular ROS production was determined by the chloromethyl-2',7'-dichlorodihydro-fluorescein diacetate system. We found that the intracellular ROS production by X-irradiation was completely suppressed by the addition of edaravone. The accumulation and phosphorylation of p53 and the expression of p21(WAF1), a target protein of p53, which were induced by X-irradiation, were also suppressed by adding edaravone. We conclude that the free radical scavenger edaravone suppresses X-ray-induced apoptosis in MOLT-4 cells by inhibiting p53.     

富勒醇对小鼠γ射线辐射损伤的防护作用

目的研究C60衍生物富勒醇对小鼠~(60)Coγ射线辐射损伤的防护效果。方法ICR小鼠于照射前5d至照后7d连续腹腔注射富勒醇,~(60)Coγ射线全身均匀照射,照射剂量分别为5Gy和8Gy,照射剂量率1.0Gy/min,测定5Gyγ射线照射下小鼠体重变化,照后7d胸腺、脾脏指数外周血白细胞;8Gyγ射线照射下30d存活率和平均生存时间。结果富勒醇能减轻~(60)Coγ射线辐射所引起的外周血白细胞、血小板降低,胸腺和脾脏萎缩;提高小鼠生存率,延长存活时间。结论富勒醇对~(60)Coγ射线照射的小鼠具有一定的防护作用。     

In vivo gamma-rays induced initial DNA damage and the effect of famotidine in mouse leukocytes as assayed by the alkaline comet assay

Ionizing radiation induces a variety of lesions in DNA, each of which can be used as a bio-indicator for biological dosimetry or the study of the radioprotective effects of substances. To assess gamma ray-induced DNA damage in vivo in mouse leukocytes at various doses and the effect of famotidine, blood was collected from Balb/c male mice after irradiation with 4 Gy gamma-rays at different time intervals post-irradiation. To assess the response, mice were irradiated with doses of gamma-rays at 1 to 4 Grays. Famotidine was injected intra-peritoneally (i.p) at a dose of 5 mg/kg at various time intervals before irradiation. Four slides were prepared from each sample and alkaline comet assay was performed using standard protocols. Results obtained show that radiation significantly increases DNA damage in leukocytes in a dose dependent manner (p < 0.01) when using appropriate sampling time after irradiation, because increasing sampling time after irradiation resulted in a time dependent disappearance of DNA damage. Treatment with only 5 mg/kg famotidine before 4 Gy irradiation led to almost 50% reduction in DNA damage when compared with those animals which received radiation alone. The radioprotective capability of famotidine might be attributed to radical scavenging properties and an anti-oxidation mechanism.     

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.     

银耳多糖辐射防护作用的研究

目的 研究银耳多糖对辐射损伤小鼠的保护作用。方法 采用小鼠30天存活率和外周血液学参数考察银耳多糖对辐射损伤小鼠的保护作用。结果 小鼠在接受8Gy伽玛射线照射前连续三天以18,54,72 mg/kg剂量腹腔注射银耳多糖,可以明显减轻照射对小鼠造成的损伤,使存活率增强,存活天数延长。外周血中血红蛋白含量、白细胞数、红细胞数在照射后第14,18天保持较高水平,与单纯照射组相比有统计学意义(P < 0.05)。结论 银耳多糖对辐射损伤小鼠有较好的保护作用。     

Influence of seed extract of Syzygium Cumini (Jamun) on mice exposed to different doses of gamma-radiation

The radioprotective activity of the hydroalcoholic extract of jamun seeds (SCE) was studied in mice exposed to different doses of gamma radiation. The mice were injected with 0, 5, 10, 20, 40, 60, 80, 100, 120, 140 or 160 mg/kg body weight of SCE, before exposure to 10 Gy of gamma radiation, to select the optimum dose of radiation protection. The 80 mg/kg SCE was found to offer highest protection, therefore, further studies were carried out using this dose. The drug was more effective when administered through the intraperitoneal route at equimolar doses than the oral route. Since higher survival was observed for the i.p. route (50%), than the oral route (29.2%), all other studies were carried out by injecting SCE intraperitoneally. The mice treated with 80 mg/kg body weight SCE intraperitoneally before exposure to 6, 7, 8, 9, 10 and 11 Gy of gamma radiation showed reduction in the symptoms of radiation sickness and mortality at all exposure doses and caused a significant increase in the animal survival when compared with the concurrent double distilled water (DDW) + irradiation group. The SCE treatment protected mice against the gastrointestinal as well as bone marrow deaths and the DRF was found to be 1.24.     

5,7-Dihydroxychromone-2-carboxylic acid and it's transition-metal (Mn and Zn) chelates as non-thiol radioprotective agents

5,7-Dihydroxychromone-2-carboxylic acid (DHCCA) and its related complexes with manganese and zinc were prepared and evaluated for radioprotection activity against gamma irradiation in mice. The LD(50) values were found to be more than 1500 and 1000 mg/kg for DHCCA and it's complexes, respectively. For studying radioprotective effects, 1.0 mmol/kg and 0.5 mmol/kg doses of compounds were administrated subcutaneously 24 h prior to 8.2 Gy gamma irradiation. The percentages of 30-day survival of mice for these compounds were 26%-50%. DHCCA exhibited significant action in delaying deaths as well as effective protection against gamma rays-induced mortality compared to reference drug amifostine. Amifostine provides effective radiation protection when administrated immediately prior to radiation exposure, but administration of DHCCA, even 24 h prior to gamma irradiation, provides a significant protection.     

苞叶雪莲水提物对小鼠生殖细胞辐射防护作用的研究

目的 初步研究苞叶雪莲水提物对小鼠生殖细胞的辐射防护作用。方法 以辐射损伤小鼠作为研究对象,分别给予不同剂量的苞叶雪莲水提物灌胃14d后接受4Gy的X射线一次性全身照射,后继续灌胃,在照射后第35天处死小鼠,测量小鼠精子畸形率。结果 各给药组+照射组与照射组相比较,低剂量、中剂量、高剂量小鼠精子畸形率低于照射组。其中,中剂量组和高剂量组明显低于照射组,差异有统计学意义,P<0.05。结论 苞叶雪莲水提物中的活性成分对小鼠的生殖细胞有一定程度的防辐射损伤作用。     

Radioprotective effect of chitosan in sub-lethally X-ray irradiated mice

The radioprotective effect of chitosan was studied in mice following whole-body X-ray irradiation. C3H/He mice were exposed to 7 Gy, and their survival rates were examined. The survival rates of chitosan-diet mice were about 20% higher than those of mice on a standard diet, and the rates dropped sharply to a plateau at day 10 after X-ray irradiation. The chitosan-diet mice had an increased weight ratio of spleen to body within the experimental period. The leukocyte, thrombocyte, and erythrocyte counts as well as the hematocrit and hemoglobin levels were recovered significantly and more rapidly in the chitosan-diet mice than the standard-diet mice at day 14 after irradiation. The scavenging abilities of chitosan were evaluated by the ESR spin-trapping method. These observations suggested that chitosan led to hematopoetic activation and leukocytogenesis in mice after sub-lethal dose irradiation, and that the biological response might be caused by radical trapping or scavenging.     

硼卡钠对急性辐射损伤小鼠的防护作用

目的 考察硼卡钠(sodium borocaptate,BSH)对急性辐射损伤小鼠的防护作用。方法 以BSH为受试物,用⁶⁰Co γ射线对小鼠进行一次性全身照射,照射剂量为6 Gy,剂量率为0.8 Gy/min。照射后第3天、第14天检测外周血细胞计数,并于照射后第14天检测小鼠脏器指数。结果 照后第3天,BSH高剂量组血小板计数显著增加(P <0.05);照后第14天,与模型组比较,BSH中剂量组血小板计数显著增加(P < 0.01),胸腺指数、脾脏指数均显著升高(P < 0.05)。结论 BSH能显著提高辐照后小鼠的血小板水平,对急性辐射损伤小鼠免疫系统有保护作用。     

Radioprotective potential of an herbal extract of Tinospora cordifolia

A preparation of Tinospora cordifolia (RTc) administered i.p. (200 mg/kg b.w.) to strain "A" male mice 1 h before whole body gamma-irradiation was evaluated for its radioprotective efficacy in terms of whole body survival, spleen colony forming units (CFU), hematological parameters, cell cycle progression, and micronuclei induction. Preirradiation treatment with RTc rendered 76.3% survival (30 days), compared to 100% mortality in irradiated control and prevented radiation induced weight loss. On 10th postirradiation day, the endogenous CFU counts in spleen were decreased with increasing radiation doses 12.0 (5 Gy), 2.16 (7.5 Gy) and 0.33 (10 Gy) but pre-irradiation administration of 200 mg/kg b.w. of RTc increased CFU counts to 31.16, 21.83 and 3.00 respectively. Pre-irradiation RTc treatment could restore total lymphocyte counts (TLC) by the 15th day to normal. It also increased the S-phase cell population that was reduced following 2 Gy irradiation in a time dependent manner. 2 Gy irradiation-induced micronuclei were also decreased by a pre-irradiation administration of RTc from 2.9 to 0.52%. Because the radioprotective manifestation of RTc observed in several systems in experimental animals can be exploited for human applications.     

Radioprotection of sensitive rat tissues by oligoelements Se, Zn, Mn plus Lachesis muta venom

In this study we first evaluated the general radioprotective efficacy of Se, Zn and Mn (4 μg/ml each) plus Lachesis muta venom (4 ng/ml) combination (O-LM) by determining survival on rats irradiated with lethal doses of gamma-rays. The aim of the second part of the study was to investigate the O-LM ability to prevent ionizing radiation-induced damage on small intestine, bone marrow and submandibular glands. Hence, histological characteristics and functional studies, together with proliferation and apoptotic marker levels on whole body irradiated rats with a 5 Gy dose were evaluated. Results show that all animals of the untreated group died after whole body irradiation with 8 and 10 Gy while 60 day-survival was more than 80% and 40% in O-LM-treated animals, respectively. Histopathological examinations revealed a high degree of small intestine and submandibular gland radioprotection 3 days post-irradiation. O-LM inhibited histological damage on small intestine, restoring the radiation-induced reduction in villous height and crypt number. O-LM prevented radiation-induced loss of salivary gland function and morphological alterations. These effects were associated to a complete inhibition of radiation-induced apoptosis. Furthermore, studies performed 30 days post-irradiation revealed that O-LM significantly improved bone marrow repopulation, increasing all medullar progenies to the extent of the non-irradiated animals, and completely prevented permanent submandibular gland alterations. Based on the present results and taking into account that O-LM is being safely administered in phase I clinical trial as an immunomodulator, we conclude that O-LM is a non-toxic promising approach to achieve radioprotection for patients undergoing radiotherapy.     

Evaluation of radioprotective effects of Rajgira (Amaranthus paniculatus) extract in Swiss albino mice

The radioprotective efficacy of aqueous extract of Rajgira (Amaranthus paniculatus) leaves against whole body gamma radiation was studied in Swiss albino mice. The oral administration of Rajgira extract at 800 mg/kg body weight/day for 15 consecutive days before whole body exposure to radiation was found to be effective with the LD50/30 values of 6.33 and 8.62 Gy for irradiation alone and Rajgira+irradiation group, respectively, giving a dose reduction factor of 1.36. This effect of Rajgira accompanied the increased endogenous spleen colonies and the spleen weight without any side effect or toxicity, as well as the modulation of the radiation-induced decrease of reduced glutathione and the radiation-induced increase in lipid peroxidation assessed in the liver and the blood.     

抗氧化物质在辐射防护中的作用

电离辐射对生物体构成损伤,一是辐射能量传递的直接作用,二是通过水在辐解反应中产生的自由基所引起的损伤的间接作用,氧化损伤是辐射对机体损伤的重要机制之一。抗氧化物质可以清除自由基,理应具有辐射防护作用。     

Modulation of gamma radiation-inflicted damage in Swiss albino mice by an alcoholic fraction of Podophyllum hexandrum rhizome

A partially characterized extract of Podophyllum hexandrum rhizomes was studied for its radioprotective potential in mice. A major portion of the podophyllotoxin was obtained from the extract by further fractionation. Acute toxicity and maximum tolerated dose (MTD) of a single intraperitoneal dose of the extract were studied in mice to evaluate the toxicity of the extract, if any. Radioprotective efficacy was determined in terms of survival against 10 Gy whole-body irradiation (WBI), protection against 1 Gy-induced chromosomal aberration (CA), and estimation of dose reduction factor (DRF) in irradiated and extract pretreated mice. The MTD was observed to be 60 mg/kg of body weight, whereas a dose of 90 mg/kg of body weight yielded 50% death in mice within 72 hours of intraperitoneal administration of the extract. A dose range of 15-20 mg/kg of body weight administered 2 hours before 10 Gy WBI of mice yielded 66% survival, while administration of 10-15 mg/kg of body weight of the extract 1 hour before WBI yielded more than 90% survival. A DRF of 1.625 was estimated for 10 and 15 mg/kg of body weight of the extract administered 1 hour before WBI. Further studies on modulation of 1 Gy-induced CA revealed significant radioprotective efficacy of the extract in mouse bone marrow cells. Partial removal of podophyllotoxin was useful in reducing toxicity of the extract without altering its radioprotective efficacy.