OBJECTIVETo explore the effect of Renshen Yangrong Decoction (人参养荣汤, RYD) in protecting bone marrow from radiation injury.

METHODSOne hundred and eighty Kuming mice were subjected to the three tests for anti-radiation injury effect evaluation, i.e. the test of peripheral white blood cell (WBC) count, the test of bone marrow nucleated cell count, and the bone marrow micronucleus test, using 60 mice for each test. The mice in each test were divided into 6 groups: the blank control group, the model control group, the positive control group treated by Shiyiwei Shenqi Tablet (十一味参芪片, 1.0 g/kg), and three RYD groups treated with high (42.0 g/kg), moderate (21.0 g/kg), and low (10.5 g/kg) doses of crude drugs of RYD, with 10 mice in each group. The treatment was given by gastrogavage perfusion continuously for 7-14 days before mice received (60)Co-γ ray radiation and continued until the end of the experiment. The body weights of the mice were monitored, the changes in peripheral WBC and bone marrow nucleated cells were counted, and the variation in bone marrow micronucleated cells was observed on the respective appointed days.

RESULTSA significant decrease in body weight, peripheral WBC count, and bone marrow nucleated cell count, as well as marked changes in bone marrow micronucleated cells were observed in the mice after radiation, indicating that the radiation injury model was successfully established. As compared with the model control group, the decrease in body weight, peripheral WBC count, and bone marrow nucleated cell count, as well as the increase in bone marrow micronucleus cell count in the high dosage RYD treated group were obviously inhibited or lessened (P<0.05 or P<0.01).

CONCLUSIONRYD showed obvious protective effect in mice with bone marrow injury induced by radiation.

Animals ; Body Weight ; drug effects ; radiation effects ; Bone Marrow ; drug effects ; pathology ; radiation effects ; Bone Marrow Cells ; drug effects ; pathology ; radiation effects ; Drugs, Chinese Herbal ; pharmacology ; Leukocyte Count ; Mice ; Radiation Injuries ; blood ; pathology ; prevention & control ; Radiation-Protective Agents ; pharmacology

The aim of this study was to investigate the effects of D-methionine (D-met) on the hematopoietic system injury in irradiated mice. C57BL/6 mice were divided into control group, irradiated group, 300 mg/kg D-met plus irradiation group and 1000 mg/kg D-met plus irradiation group. The control mice received sham irradiation, and the mice in remainder groups were exposed to 7.5 Gy; 1,4,8 Gy and 1 Gy of (137)Cs γ-ray respectively, were used to detect the survival rate, survival rate of bone marrow cells, WBC and its differential counts as well the colony formation ability in irradiated mice, respectively. The D-met was intraperitoneally injected to mice at 30 min before irradiation. The results showed that 300 and 1000 mg/kd D-met did not obviously enhance the survival rate of mice exposed to 7.5 Gy; the 10(-2),10(-3),10(-4) mol/L D-met significantly increased the survival rate of bone marrow cells in mice exposed to 1,4,8 Gy; 300 and 1000 mg/kg D-met even so increased the WBC count of peripheral blood in mice exposed to 1 Gy, but there was no statistical difference as compared with irradiated alone mice, moreover 300 and 1000 mg/kg D-met could obviously promote the colony formation ability of bone marrow cells in irradiated mice, the CFU-GM count was higher than that in 1 Gy irradiated mice (P < 0.05). It is concluded that the D-met can effectively mitigate the marrow cell injury resulted from irradiation, enhance the survival rate of bone marrow cells in irradiated mice, promote the recovery of hematopoietic function from radiation injury in mice.
Animals ; Bone Marrow Cells ; drug effects ; radiation effects ; Hematopoietic System ; drug effects ; radiation effects ; Leukocyte Count ; Methionine ; pharmacology ; Mice ; Mice, Inbred C57BL ; Radiation Injuries ; prevention & control

This study was aimed to investigate the radioprotective effects of recombinant human interleukin-12 (rhIL-12) on monkey hematopoietic system, and to provide experimental evidence for future clinical prophylaxis and treatment for patients who suffered from acute radiation syndrome. In in vitro study, the effect of rhIL-12 in different concentrations (0, 1, 5, 25, 125 and 625 ng/ml) on colony forming capacity of human or monkey bone marrow-derived mononuclear cells was examined in methylcellulose H4434 medium. In in vivo study, the acute radiation syndrome model was established in 11 Rhesus monkeys which received lethal total body irradiation by 6 Gy (60)Co γ in single time irradiation. The irradiated monkeys were randomly divided into 3 subgroups: control group (n = 4) which received subcutaneous PBS injection, rhIL-12 single-dose group (n = 3) which received subcutaneous single injection of rhIL-12 (4 µg/kg) at 2 h after irradiation, and multiple-dose group (n = 4) which received subcutaneous injection of rhIL-12 (1 µg/kg per injection) at 2 h, day 3, 6 and 9 after irradiation respectively. Peripheral blood cells were counted before and after irradiation every other day. The survival status of animals were observed daily. In vitro test results showed that different concentrations of rhIL-12 obviously promoted human and healthy monkeys' bone marrow mononuclear cells to form various hematopoietic progenitor cell colonies, especial CFU-E and CFU-GM. All animals in control group died within 22 d after lethal total body irradiation, average survival time was (20.3 ± 1.2) d. Only one monkey in multiple-dose group died due to anemia on day 17. All monkeys in single-dose group survived. Compared with control group, rhIL-12-administrated monkeys' white blood cell count, hemoglobin level, platelet and reticulocyte counts showed faster recovery from high dose radiation. It is concluded that the rhIL-12 treatment can promote the bone marrow hematopoietic stem/progenitor cell colony formation in vitro and protect lethally-irradiated monkeys. There is an obvious therapeutic effect of rhIL-12 on monkeys suffered from bone marrow failure caused by severe acute radiation exposure.
Animals ; Bone Marrow Cells ; cytology ; drug effects ; radiation effects ; Cells, Cultured ; Hematopoietic Stem Cells ; drug effects ; radiation effects ; Humans ; Interleukin-12 ; pharmacology ; Macaca mulatta ; Radiation-Protective Agents ; pharmacology ; Recombinant Fusion Proteins ; pharmacology

The aim of this study was to investigate the effect of WR2721(amifostine) against bone marrow hematopoietic damage of mice exposed to 6.5 Gy of (60)Co-γ ray. A total of 60 C57/BL6J mice was divided into 3 groups:normal group (mice were injected with physiological salt solution), irradiation group (mice were injected with physiologic salt solution before irradiation) and WR2721 group (mice were injected with WR2721 before irradiation). The WBC, neutrophil (Neut), Plt and RBC levels in peripheral blood of 3 group mice were counted within 60 days after irradiation; the bone marrow nuclear cells (BMNC) were counted at 2 and 24 hours after irradiation; the hematopoietic stem/progenitor cell (LK/LSK) level and colony formation capability were detected by flow cytometry at 2 and 24 hours after irradiation. The results indicated that the counts of WBC and neut at 4 and 18 days, Plt at 7-18 days and RBC at 10-30 day after irradiation in WR2721 group were higher than those in irradiation group (P < 0.05); the BMNC, LSK and LK levels obviously increased at 24 hours after irradiation (P < 0.05), the CFU-GEMM, CFU-GM, CFU-MK BFU-E and CFU-E all significantly increased at 2 and 24 hours after irradiation (P < 0.01), as compared with irradiation group. It is concluded that WR2721 can effectively alleviate early hematopoietic damage and promote the fast recovery of peripheral blood cells in mice exposed to γ-ray, suggesting that the WR2721 has significant radioprotective effect on hematopoietic system.
Amifostine ; pharmacology ; Animals ; Blood Cell Count ; Bone Marrow Cells ; cytology ; drug effects ; radiation effects ; Gamma Rays ; Hematopoietic Stem Cells ; cytology ; drug effects ; radiation effects ; Male ; Mice ; Mice, Inbred C57BL ; Radiation-Protective Agents ; pharmacology ; Whole-Body Irradiation

OBJECTIVETo explore the effects of xue-bao capsules on injury of radio-or chemo-therapy in mice, in order to provide rationale behind clinical trials.

METHODxue-xu (deficiency of blood) model in mice was induced by radiation or cyclophosphamide. Leucocyte (WBC), erythrocyte (RBC), hemoglobin (Hb) and platelet (Pt) in peripheral blood as well as CFU-E and CFU-Gm in bone marrow were counted.

RESULTCFU-E and CFU-Gm in normal mice were promoted by this drug. The reduction of WBC, RBC and Hb in peripheral blood as well as CFU-E and CFU-Gm in bone marrow owing to the 3.5 Gy of 60Co radiation were antagonized by the drug. It had also antagonized cyclophosphamide induced the reduction of WBC, RBC and Pt in peripheral blood.

CONCLUSIONxue-bao capsules has the effects against the adverse reactions of radio-or-chemo-therapy.

Animals ; Bone Marrow Cells ; cytology ; drug effects ; radiation effects ; Capsules ; Cell Count ; Cells, Cultured ; Cyclophosphamide ; toxicity ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Erythrocyte Count ; Erythroid Precursor Cells ; drug effects ; radiation effects ; Female ; Granulocyte Precursor Cells ; drug effects ; radiation effects ; Leukocyte Count ; Male ; Mice ; Plants, Medicinal ; chemistry ; Platelet Count ; Radiation Injuries, Experimental ; blood ; pathology ; Random Allocation ; Whole-Body Irradiation ; adverse effects

This study was purposed to investigate the protective effects of lipoprotein HS-6101(6101) on rhesus monkey total body irradiated with 7.0 Gy ⁶⁰Coγ-ray. A total of 30 health adult rhesus monkeys were randomly divided into symptomatic therapy (ST), WR2721 and HS-6101 30, 90 and 270 mg/kg groups (n = 6), the rhesus monkeys of each groups were injected with physiological saline 0.3 ml/kg, WR-2721 30 mg/kg, or HS-6101 30, 90 and 270 µg/kg, respectively. All agents were once intramuscularly injected at 1 hr prior irradiation. General observation, peripheral blood cell counts, colony forming unite assay of bone marrow hemopoietic progenitor cells, and histopathological examination were performed. The results showed that animals in symptomatic therapy group begin to die on the 13(th) day and 4 animals died within 24 days, the average survival time was 18.2 ± 4.3 days; 2 animals in WR-2717 groups died on day 15.8 and day 18.5 post irradiation respectively. 1 animal in HS-6101 270 mg/kg group died on day 35.8, all other animals survived. Nadirs of peripheral blood white blood cells, neutrophils and platelets of animals in HS-6101 treatment groups were significantly higher than those in other 2 groups including ST and WR-2721 groups, and the hemopoietic recovery were also significantly speeding up(P < 0.05 and 0.01). In vitro results showed that HS-6101 obviously promoted 7.0 Gy ⁶⁰Coγ irradiated monkey's bone marrow mononuclear cells to form various hematopoietic progenitor cell colonies (P < 0.05 and 0.01) . Compared with symptomatic therapy and WR-2717 groups, bone marrow histopathological changes in HS-6101 treatment groups showed more active hemopoietic cell proliferation and higher density structure. It is concluded that HS-6101 90 µg/kg treatment can promote the bone marrow recovery of 7.0 Gy ⁶⁰Coγ irradiated monkey, alleviate their animal symptom, simplify the treatment measures and improve the animal survival rate. The HS-6101 shows remarkable radioprotective effects as compared with the currently internationally acknowledged radioprotectant of WR-2721.
Amifostine ; Animals ; Blood Cell Count ; Blood Platelets ; Bone Marrow ; Bone Marrow Cells ; Hematopoietic Stem Cells ; Hematopoietic System ; drug effects ; radiation effects ; Lipoproteins ; pharmacology ; Macaca mulatta ; Radiation Injuries ; drug therapy ; Survival Rate

OBJECTIVETo observe the effect of Shuanghuang Shengbai granule on mice leukopenia induced by ip cyclophosphamide (CTX) or radiation.

METHODMice leukopenia models were induced by ip CTX or radiation, and then treated with Shuanghuang Shengbai granule per oral. The peripheral hemogram, thymus index, spleen index, bone marrow nucleated cell (BMNC) and colony forming unit-spleen (CFU-S) were detected. The bone marrow cell differentiation was examined. The pathological slices of bone marrow were observed.

RESULTShuanghuang Shengbai granule could increase the WBC, BMNC, CFU-S of model mice significantly; Shuanghuang Shengbai granule could make the granulocyte and erythrocyte index recovered to normal level and it could also protect the bone marrow hemotopoietic microenvironment from the harm of radiation.

CONCLUSIONShuanghuang Shengbai granule has apparent leukogenic function.

Animals ; Bone Marrow ; ultrastructure ; Bone Marrow Cells ; drug effects ; pathology ; radiation effects ; Cell Count ; Cesium Radioisotopes ; Cyclophosphamide ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Erythrocyte Count ; Granulocytes ; drug effects ; pathology ; radiation effects ; Leukocyte Count ; Leukopenia ; chemically induced ; pathology ; Male ; Mice ; Mice, Inbred ICR ; Plants, Medicinal ; chemistry ; Random Allocation ; Stem Cells ; drug effects ; pathology ; radiation effects ; Whole-Body Irradiation

The radioprotective activity of extracts from the red seaweed Callophyllis (C.) japonica was investigated in mice that underwent whole-body exposure to gamma radiation. A methanol extract of C. japonica and its fractions [hexane, ethyl acetate (EtOAc), butanol and the remaining H(2)O] were used. Each fraction (100 mg/kg body weight) was administered intraperitoneally (i.p.) 2 times into the BALB/c mice, once at 1 and once at 24 h before exposure to 9 Gray (Gy) of gamma radiation. Pre-irradiation administration of the hexane and EtOAc fractions saved the mice, with their survival rates being greater than 80% at 30 days post-irradiation; the mice that were pretreated with the other fractions showed survival rates lower than 20% over the same time period. To examine the effect of each C. japonica fraction on the survival of intestinal and bone marrow stem cells, the number of intestinal crypts and bone marrow cells in the gamma-irradiated mice were examined. Pre-treatment of mice (i.p., 100 mg/kg body weight at 1 and 24 h before irradiation) with the hexane or EtOAc fraction prior to 6-Gy irradiation significantly protected the number of jejunal crypts and bone marrow cells at 9 days after irradiation. These findings suggest that certain extracts from C. japonica, when they are administered prior to irradiation, play an important role in the survival of irradiated mice, and this is possibly due to the extracts protecting the hematopoietic cells and intestinal stem cells against gamma irradiation.
Acetates ; Animals ; Bone Marrow Cells/drug effects/*radiation effects ; Cell Survival/drug effects ; Female ; Gamma Rays ; Hexanes ; Intestinal Mucosa/cytology/drug effects/radiation effects ; Jejunum/cytology/drug effects/radiation effects ; Mice ; Mice, Inbred BALB C ; Plant Extracts/*pharmacology ; Radiation Injuries, Experimental/prevention & control ; Radiation-Protective Agents/*pharmacology ; *Seaweed ; Whole-Body Irradiation/*veterinary

To study the expression of the bFGF and its receptor in the mouse bone marrow by treatment with acute radioactive injury and Ligustrazine, 56 mice were divided into 3 groups: normal group, radiation-injured group and Ligustrazine group. After irradiation by 6.0 Gy 60Co gamma-ray, each mouse was orally given 0.1 ml Ligustrazine twice a day for 13 days in Ligustrazine group, and each mouse in radiation injured group was orally given equal amount of saline. On the 3rd, 7th, 14th day after irradiation, bone marrow mono-nuclear cells (BMMNC) were counted, and the expression levels of bPGF and bFGFR in bone marrow were evaluated by immunohistochemistry and flow cytometry analysis respectively. On the 3rd, 7th, 14th day after irradiation, expression of bFGF in bone marrow were significantly lower than in normal group (P<0.05 or P<0.01). Expressions of bFGF and bFGFR were much higher in Ligustrazine treated group than that in the control group (P<0.05 or P<0.01). Ligustrazine potentiate the expression of bFGF and bFGFR in bone marrow MNC to recover the bone marrow hematopoiesis inductive microenvironment, which is one of the mechanisms by which Ligustrazine rebuild the bone marrow hematopoiesis after acute radioactive injury.
Bone Marrow Cells/metabolism ; Fibroblast Growth Factor 2/*biosynthesis ; Hematopoiesis/drug effects ; Pyrazines/*pharmacology ; Radiation Injuries, Experimental/*metabolism ; Radiation-Protective Agents/pharmacology ; Receptors, Fibroblast Growth Factor/*biosynthesis

OBJECTIVETo investigate the effect of SS8, a monomer extracted from Spatholobus suberectus Dunn used for invigorating the circulation of blood, on proliferation of hematopoietic progenitor cells in mice with bone marrow depression.

METHODThe method of semi-solid culture with methylcellulose of CFU-GM, CFU-E, BFU-E, CFU-Meg was adopted in bone marrow depressed mice which were treated with SS8 for a long time.

RESULTThe experimental data demonstrated that the numbers of CFU-GM, CFU-E, BFU-E, CFU-Meg in bone marrow depressed mice were raised distinctly under the control of SS8 as compared with those of contrast group. The effect of SS8 became stronger as time went on and the dosage rose.

CONCLUSIONSS8 can distinctly stimulate the proliferation of hematopoietec progenitor cells in mice with bone marrow depression in a time-and-dosagedependent manner.

Animals ; Bone Marrow Cells ; radiation effects ; Cell Division ; drug effects ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Erythroid Precursor Cells ; drug effects ; radiation effects ; Fabaceae ; chemistry ; Female ; Hematopoietic Stem Cells ; cytology ; drug effects ; radiation effects ; Male ; Mice ; Plants, Medicinal ; chemistry ; Whole-Body Irradiation