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。     

Protective Effect of Polysaccharides Isolated from <i>Tremella fuciformis</i> against Radiation-induced Damage in Mice

WTF-B, a type of water-soluble homogeneous polysaccharide, was isolated and purified from Tremella Fuciformis. To investigate the radioprotective effect of WTF-B, we employed a 30-day survival assay. Mice were treated with WTF-B once per day for three consecutive days before 8-Gy gamma irradiation. The treatment groups receiving 54 and 72 mg/kg body weight (b.w.) of WTF-B showed 50% survival post-irradiation. The hematological parameters of the peripheral blood indicated that WTF-B, when administered at doses of 72 mg/kg b.w., significantly restored hemoglobin, white blood cell counts and red blood cell counts by the 14th day and 18th day. In addition, spleen colony forming units (CFU-S), the number of nucleated cells in bone marrow (BMNC) and spleen index were used to investigate the radioprotective effect of WTF-B on the hematopoietic system. The treatment groups receiving WTF-B at 18, 54 and 72 mg/kg b.w. doses presented significantly higher BMNC compared to radiation-only group. The group administered 72 mg/kg b.w. WTF-B presented a significant change in CFU-S compared to the radiation-only group. We also completed micronucleus and chromosome aberration assays to explore genotoxicity. The results of those assays indicated that the number of micronuclei induced by 2-Gy irradiation in a group treated with 72 mg/kg b.w. WTF-B decreased from 30.30‰ to 11.32‰. The chromosomal aberration produced by 3-Gy irradiation in the group receiving 72 mg/kg b.w. WTF-B decreased from 56.01% to 28.13%. The results of the present study indicate a potential use for WTF-B as a radioprotector.     

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。     

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.     

Radioprotective effects of Sipunculus nudus L. polysaccharide combined with WR-2721, rhIL-11 and rhG-CSF on radiation-injured mice

This study investigated the radioprotective effect of Sipunculus nudus L. polysaccharide (SNP) in combination with WR-2721, rhIL-11 and rhG-CSF on irradiated mice. A total of 70 Imprinting Control Region (ICR) mice were divided into seven groups: the control group, the model group and five administration groups. All groups, except the control group, were exposed to a 5 Gy ⁶⁰Co γ-ray beam. Blood parameters [including white blood cell (WBC), red blood cell (RBC) and platelet counts and hemoglobin level] were assessed three days before irradiation, and the on the 3rd, 7th and 14th days after irradiation. Spleen, thymus and testicular indices, DNA contents of bone marrow cells, bone marrow nucleated cells, sperm counts, superoxide dismutase (SOD), malondialdehyde (MDA), testosterone and estradiol levels in the serum were assessed on the 14th day after irradiation. The combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF exerted synergistic recovery effects on peripheral blood WBC, RBC and platelet counts and hemoglobin levels in irradiated mice, and synergistic promotion effects on spleen, thymus, testicle, bone marrow nucleated cells and sperm counts in irradiated mice. The synergistic administration increased the serum SOD activities and serum testosterone content of irradiated mice, but synergy decreased the content of serum MDA and estradiol in irradiated mice. These results suggest that the combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF should increase the efficacy of these drugs for acute radiation sickness, protect immunity, hematopoiesis and the reproductive organs of irradiated-damaged mice, and improve oxidation resistance in the body.     

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.     

Effect of Tinospora cordifolia on gamma ray-induced perturbations in macrophages and splenocytes

Tinospora cordifolia (RTc) has already been reported to protect whole-body lethally irradiated mice. This study has focussed on certain aspects of immuno-competence, which are adversely affected by irradiation. This study included estimation of spleen size, cell count, DNA fragmentation and apoptosis in splenocytes. The adherence, spreading and phagocytic activities of macrophages were also assessed. Cytokines in serum and anti-oxidants in plasma were also estimated. Administration of RTc (200 mg/kg.b.wt.) one hour before irradiation showed recovery of spleen weight from 49% of control in irradiated group to 93%; apoptosis from 19% to 2.8%; DNA fragmentation from 43% to 20.4%; macrophage adherence form 75% of control to 120% and macrophage spread size from 8 microm to 15 microm. RTc also stimulated proliferation in splenocytes in a dose-dependent manner. RTc administration before irradiation also increased levels of IL-1beta and GM-CSF levels, from 56 pg/ml and 53 pg/ml respectively in irradiated group to 59 pg/ml and 63 pg/ml. Similarly, radiation-induced decrease of anti-oxidant potential of plasma (32 Fe(2+) equiv.) as compared to control (132 Fe(2+) equiv.) was countered by administration of RTc before irradiation (74.2 Fe(2+) equiv.) RTc treatment thus reveals several radio-protective mechanisms.     

Polysaccharide isolated from Parmelia tinctorum ameliorates ionizing irradiation-induced damage in mice

In this study, WPT-A, a type of water-soluble homogeneous lichen polysaccharide, was isolated and purified from Parmelia tinctorum. We investigated whether WPT-A has radioprotective effects when administered before total-body irradiation (TBI). Mice were treated with WPT-A via intraperitoneal injection (i.p.) once per day for three consecutive days prior to 7, 7.5, 8.5, 10 or 10.5-Gy TBI. Our results indicated that the survival rate was enhanced at a range of levels of TBI. The calculated dose reduction factor (DRF) was 1.2. White blood cell (WBC) counts, spleen colony forming units (CFU-S) and bone marrow nucleated cell (BMNC) counts were used to investigate the radioprotective effects of WPT-A on the hematopoietic system. The treatment groups received WPT-A at 20, 50 and 80 mg/kg b.w. doses before 6.5-Gy TBI and showed significantly higher BMNC and WBC counts compared with the radiation-only group. The groups administered 50 and 80 mg/kg b.w. WPT-A showed a significant increase in CFU-S compared with the radiation-only group. We also carried out a single cell gel electrophoresis assay to explore the radioprotective effects of WPT-A on DNA damage. The results from single-cell gel electrophoresis of peripheral blood leukocytes showed that WPT-A attenuated radiation-induced DNA damage. These results indicate a potential use for WPT-A as a radioprotector.     

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。     

Radioprotection by Rhodiola imbricata in mice against whole-body lethal irradiation

Rhodiola imbricata, an Indian medicinal plant, was investigated for protection against whole-body lethal gamma irradiation (10 Gy)-induced mortality in Swiss albino strain "A" mice. The maximum tolerance dose values for aqueous (RD-I) and aqua-alcoholic (RD-II) extracts were 1,100 and 1,300 mg/kg of body weight, respectively. Pre-irradiation administration of RD-I produced >90% survival, while RD-II produced >83% survival beyond the 30-day observation period. The optimal radioprotective dose for RD-I as well as RD-II was 350 mg/kg of body weight; the aqua-alcoholic extract, however, had an advantage over the aqueous extract at lower as well as at higher doses. The optimal time interval between administration of extract and irradiation was 30 minutes for both RD-I and RD-II. The number of colony-forming units per spleen in irradiated mice was 1.91 +/- 0.15, while in mice given RD-I or RD-II, 30 minutes before irradiation (10 Gy), it increased to 17.3 +/- 0.67 and 15.6 +/- 0.61, respectively. These findings have important implications in the development of a suitable radioprotector of herbal origin.     

Gamma-tocopherol-N,N-dimethylglycine ester as a potent post-irradiation mitigator against whole body X-irradiation-induced bone marrow death in mice

We examined the radioprotective and mitigative effects of gamma-tocopherol-N,N-dimethylglycine ester (GTDMG), a novel water-soluble gamma-tocopherol derivative, against X-irradiation-induced bone marrow death in mice. Mice (C3H, 10 weeks, male) were injected intraperitoneally with GTDMG suspended in a 0.5% methyl cellulose solution before or after receiving of 7.5-Gy whole body X-irradiation. GTDMG significantly enhanced the 30-day survival rate when given 30 min before or immediately after the irradiation. Its mitigative activity (administered after exposure) was examined further in detail. The optimal concentration of GTDMG given immediately after irradiation was around 100 mg/kg body weight (bw) and the 30-day survival rate was 97.6 ± 2.4%. When GTDMG was administered 1, 10 and 24 h post-irradiation, the survival rate was 85.7 ± 7.6, 75.0 ± 9.7 and 36.7 ± 8.8%, respectively, showing significant mitigation even at 24 h after irradiation (P < 0.05). The value of the dose reduction factor (100 mg/kg bw, given intraperitoneally (i.p.) immediately after irradiation) was 1.25. GTDMG enhanced the recovery of red blood cell-, white blood cell-, and platelet-counts after irradiation and significantly increased the number of endogenous spleen colonies (P < 0.05). Subcutaneous (s.c.) administration also had mitigative effects. In conclusion, GTDMG is a potent radiation mitigator.     

Prevention of gamma radiation induced anaemia in mice by diltiazem

Intraperitoneal administration of diltiazem (DTZ), half an hour prior to whole body gamma irradiation (2.5, 5.0, & 7.5 Gy), showed the protection of animals from radiation-induced anaemia. Radiation exposure significantly (p < 0.001) reduced the number of pro- and normoblasts in bone marrow and RBC counts, hemoglobin (Hb), hematocrit (Hct ), and erythropoietin (EPO) level in blood, but increased myeloid / erythroid ratio. At all the radiation doses, the maximum decrease in these values was noted on the 3rd day, followed by a gradual recovery from the 7th day, but it was not recorded as normal even until the end of experimentation. In animals pretreated with DTZ, these values were measured higher at all the time periods in comparison to corresponding control, and these were almost normal at the last autopsy interval only at 2.5 Gy radiation dose. DTZ maintained the higher erythropoietin level in blood, which acted on bone marrow and spleen colony forming unit for erythroblast (CFU-E), and stimulated such cells to produce RBCs. These results confirm that DTZ has the potency to alter anaemic condition favorably through the protection of bone marrow stem cells, and subsequently it maintains the higher number of pro- and normoblasts in bone marrow, RBC counts, hemoglobin (Hb), hematocrit (Hct) percentage, and erythropoietin level in blood and the lower myeloid/erythroid ratio in bone marrow.     

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.     

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.     

Radioprotection of Swiss albino mice by plant extract Mentha piperita (Linn.)

The oral administration of Mentha extract (ME) before exposure to gamma radiation was found to be effective in increasing the frequency of radiation-induced endogenous spleen colonies. A significant increase in the weight of the spleen was observed in animals of the Mentha and radiation combined group in comparison to the irradiation-alone group on day 10 of postirradiation. Furthermore, a significant increase in the body weight of animals in the Mentha and radiation combined group was observed in all the radiation doses studied. A regression analysis of survival data yielded LD50/30 as 6.48 +/- 0.07 and 11.59 +/- 0.21 Gy for the irradiation-alone and the Mentha and radiation combined group, respectively, and produced a dose reduction factor (DRF) of 1.78. Significant increases in total erythrocyte and leucocyte counts, hemoglobin concentration, and hematocrit values were observed in the animals of the Mentha and radiation combined group in comparison to the hematological values observed in the irradiation-alone group at all radiation doses studied (6, 8, and 10 Gy). A dose-dependent decrease in reduced glutathione (GSH) content and an increase in lipid peroxidation (LPO) levels were observed in control animals. However, the animals of the Mentha and radiation combined group exhibited a significant increase in GSH content and a decrease in LPO level, but the values remained below normal. A significant increase in the serum alkaline phosphatase activity was observed in the animals of the Mentha and radiation combined group during the entire period of study, and normal range was evident at 24 h (6 Gy) and day 5 (8 Gy). However, this level could not be restored even at day 30 in 10 Gy exposed animals. Measured acid phosphatase activity in the animals of the Mentha and radiation combined group was found to be significantly lower than the respective controls and attained normal value at day 5 (6 and 8 Gy) and day 20 (10 Gy).     

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.     

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.     

Radioprotective Effects of ON 01210.Na upon Oral Administration

ON 01210.Na (Ex-RAD), a chlorobenzylsulfone derivative was investigated for its pharmacologic and radioprotective properties when administered via oral and subcutaneous (SC) routes. The goals of the study were to assess the comparative bioavailability of ON 01210.Na when administered by oral versus SC routes and to demonstrate that the oral drug delivery of ON 01210.Na afforded survival advantage similar to SC dosing. Pharmacokinetics was studied after two doses, 24 h apart, of ON 01210.Na (500 mg/kg) administered to male C3H/Hen mice (7-9 weeks) via SC injection or oral route. The dose response (100 to 750 mg/kg) and survival advantage of ON 01210.Na administered at 24 h and 15 min prior to 7.5 or 8 Gy whole body irradiation from a ¹³⁷Cs source (dose rate 1 Gy/min) were studied in these mice. Effects on the hematopoietic system were investigated by complete blood count and granulocyte-macrophage colony forming unit assay. A significant survival advantage and hematopoietic protection were observed after prophylactic oral ON 01210.Na and results were comparable to SC administration. These findings correlated well with pharmacokinetic data. Both SC and oral ON 01210.Na showed significant survival advantage against radiation toxicity and ON 01210.Na mediated hematopoietic protection plays key role in enhanced survival of mice. Oral administration holds better clinical promise as an effective countermeasure not only for early-responders in a nuclear accident, but also for the at-risk civilian population.     

Caffeine ameliorates radiation-induced skin reactions in mice but does not influence tumour radiation response.

Intramuscular administration of caffeine at a dose of 80 mg kg(-1) body weight to the gastrocnemius muscles of Swiss mice 5 min prior to local irradiation (35 Gy) of the leg delayed the progression of radiation-induced skin reactions in such animals. While 90% epilation with reddening of the skin was noted in animals treated with radiation alone, animals pretreated with caffeine suffered only partial hair loss with slight reddening of the skin on the 16th and 20th days post-irradiation. Beyond the 28th day, damage scores in irradiated feet for both the groups were similar (score 3) and remained unchanged until the 32nd day and then decreased and disappeared completely in both treatment groups by the 40th day after irradiation. In addition, the effect of caffeine on the radiation response of a mouse fibrosarcoma was investigated. Results showed that intratumoral administration of caffeine at a dose of 80 mg kg(-1) body weight 5 min prior to local exposure of tumours to 10 Gy of 60Co gamma-rays did not influence the response of tumours to radiation. The present study thus showed that although caffeine ameliorated radiation-induced skin reactions in the mouse leg, it did not affect the tumour radiation response, indicating its potential application in cancer radiotherapy.     

银杏叶黄酮抗辐射效应研究

目的:研究银杏叶中黄酮的抗辐射作用。方法:以碱性水提取法从银杏叶中分离出总黄酮(GBF),调配成低剂量(10 mg/100 ml)、中剂量(20 mg/100 ml)、高剂量(100 mg/100 ml)水溶液,分别给小鼠灌胃,10 d后,以总剂量8.5 Gy 60Co-γ射线整体辐射,再灌胃10 d,观察30 d存活率。另取小鼠,分六组(低、中、高GBF剂量组,辐射对照组,正常对照组,及环磷酰胺组),分别灌胃低、中、高剂量GBF水溶液,另三组灌胃蒸馏水,连续11 d后,低、中、高剂量GBF组及辐射对照组以总剂量1.0 Gy γ射线照射,再灌胃7 d,灌胃停止后D21 测小鼠骨髓微核率及精子畸变率及淋巴细胞测转化率。结果:低、中、高剂量GBF水溶液可分别提高辐射小鼠存活率31.7 %,25.3 %和26.5 %( P<0.05),低剂量GBF使淋巴细胞转化率显著提高(P<0.01),骨髓微核率及精子畸变率有一定程度降低。结论:低剂量银杏叶黄酮具有较强的抗辐射作用,其作用机制与提高小鼠免疫力有关。