scholarly journals Co-Therapy of Pegylated G-CSF and Ghrelin for Enhancing Survival After Exposure to Lethal Radiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Juliann G. Kiang ◽  
Min Zhai ◽  
Bin Lin ◽  
Joan T. Smith ◽  
Marsha N. Anderson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Water Consumption ◽  
Bone Marrow Cells ◽  
The Body ◽  
Photon Radiation ◽  
Vehicle Group ◽  
Spleen Weight ◽  
Histopathological Analysis ◽  
Marrow Cells

Exposure to ionizing radiation (radiation injury, RI) in nuclear-related episode is evident to be life-threatening. RI occurs at levels of organs, tissues, cytosols, or nucleus. Their mechanisms are still not fully understood. FDA approves pegylated granulocyte colony-stimulating factor (Neulasta™, Peg-G-CSF) for acute hematopoietic syndrome and has been shown to save lives after lethal RI. We aimed to test whether Ghrelin enhanced Peg-G-CSF’s efficacy to save more lives after lethal RI. B6D2F1/J female mice were used for the study. They received 9.5 Gy (LD50/30 at 0.4 Gy/min) emitted from the 60Co-γ-photon radiation facility. Peg-G-CSF was injected subcutaneously at 1 mg/kg once on days 1, 8, and 15 after irradiation. Ghrelin contains 28 amino acid and is a hunger peptide that has been shown to stimulate food intake, promote intestinal epithelial cell proliferation, elevates immunity, inhibits brain hemorrhage, and increases stress-coping. Ghrelin was injected subcutaneously at 113 μg/kg once on days 1, 2, and 3 after irradiation. Survival, body weight, water consumption, hematology, spleen weight, splenocytes, bone marrow cells, and histology of bone marrow and ileum were performed. We observed that radiation resulted in 30-days survival by 30%. RI decreased their body weights and water consumption volumes. On the 30th day post-RI, platelets and WBCs such as basophils, eosinophils, monocytes, lymphocytes, neutrophils and leukocytes were still significantly decreased in surviving mice. Likewise, their RBC, hemoglobin, hematocrit, and splenocytes remained low; splenomegaly was found in these mice. Bone marrow in surviving RI animals maintained low cellularity with high counts of fat cells and low counts of megakaryocytes. Meanwhile, ileum histology displayed injury. However, mice co-treated with both drugs 24 h after RI resulted in 30-days survival by 45% above the vehicle group. Additionally, the body-weight loss was mitigated, the acute radiation syndrome was reduced. This co-therapy significantly increased neutrophils, eosinophils, leukocytes, and platelets in circulation, inhibited splenomegaly, and increased bone marrow cells. Histopathological analysis showed significant improvement on bone marrow cellularity and ileum morphology. In conclusion, the results provide a proof of concept and suggest that the co-therapy of Peg-G-CSF and Ghrelin is efficacious to ameliorate RI.

The Effects of Yerba Maté (Ilex Paraguariensis) Consumption on IL-1, IL-6, TNF-α and IL-10 Production by Bone Marrow Cells in Wistar Rats fed a High-Fat Diet

2013 ◽  
Vol 83 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Luciana Simão Carmo ◽  
Marcelo Macedo Rogero ◽  
Mayara Cortez ◽  
Monica Yamada ◽  
Patrícia Silva Jacob ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Fat Diet ◽  
Wistar Rats ◽  
Bone Marrow Cells ◽  
The Body ◽  
Ilex Paraguariensis ◽  
Yerba Mate ◽  
High Fat ◽  
Tnf Α ◽  
Marrow Cells

An excessive consumption of a high-fat diet (HFD) results in becoming overweight or obese, which triggers a chronic inflammatory condition that is associated with a high white blood cell count. Because of the potential for yerba maté (Ilex paraguariensis) (YM) to impact obesity, this study aimed to investigate the effects of YM consumption on the hematological response and on the production of interleukin (IL)-1α, IL-6, tumor necrosis factor (TNF)-α, and IL-10 by bone marrow cells from Wistar rats fed a HFD. Male Wistar rats were fed a control (CON) or HFD diet for twelve weeks. At the end of this period, the rats received YM (1 g/kg/day body weight) for 4 weeks. After euthanasia, hemograms and myelograms were evaluated, while the bone marrow cells were cultured in the presence or absence of lipopolysaccharide (LPS) to evaluate the production of IL-1α, IL-6, TNF-α, and IL-10. The consumption of YM reduced the body weight, the body adiposity, and the cholesterol levels in HFD-fed rats. Bone marrow cells from the HFD group produced more IL-1α, IL-6, and TNF-α, and less IL-10, when compared to cells from the control group, and YM consumption reduced the IL-1α, IL-6, and TNF-α production by the cells. However, cells from the HFD rats that were stimulated with LPS increased their IL-1α, IL-6, and TNF-α production, but YM consumption did not change this result. In summary, the consumption of YM affects the production of IL-1α, IL-6, and TNF-α by bone marrow cells, promotes weight loss, decreases the number of white blood cells, and significantly improves serum cholesterol level in HFD-fed rats. However, the bone marrow cells from the HFD+YM-fed rats challenged with LPS did not show improvement in the inflammatory response compared to the cells from animals fed only a HFD that were also challenged with LPS.

Antigenotoxic effects of ascorbic acid against megestrol acetate-induced genotoxicity in mice

2005 ◽  
Vol 24 (3) ◽  
pp. 121-127 ◽  
Author(s):  
Yasir Hasan Siddique ◽  
Tanveer Beg ◽  
Mohammad Afzal
Keyword(s):  
Bone Marrow ◽  
Ascorbic Acid ◽  
Body Weight ◽  
Bone Marrow Cells ◽  
Antioxidant Properties ◽  
Megestrol Acetate ◽  
Mouse Bone Marrow ◽  
Free Oxygen Radicals ◽  
Genotoxic Damage ◽  
Marrow Cells

The genotoxicity of megestrol acetate was studied in mouse bone marrow cells using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) as parameters. Megestrol acetate (8.12, 16.25 and 32.50 mg/ kg of body weight) was injected intraperitoneally separately in different groups of animals. Both CAs and SCEs were statistically increased at 16.25 and 32.50 mg/kg of body weight. Our earlier in vitro studies show the generation of free oxygen radicals, by synthetic progestins responsible for the genotoxic damage. As the genotoxic effects of steroids can be reduced by natural products having antioxidant properties, and ascorbic acid possesses antioxidant activity, ascorbic acid (20, 40 or 60 mg/kg of body weight) administered together with megestrol acetate (32.50 mg/kg of body weight) significantly decreased CAs and SCEs, suggesting an antigenotoxic role of ascorbic acid against megestrol acetate induced genotoxic damage in mice bone marrow cells. The antigenotoxic effect was clearly dose dependent. The highest protective effect was observed at 60 mg/kg body weight of ascorbic acid treated with 32.50 mg/kg body weight of megestrol acetate.

scholarly journals Clastogenic Effects of Glyphosate in Bone Marrow Cells of Swiss Albino Mice

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Sahdeo Prasad ◽  
Smita Srivastava ◽  
Madhulika Singh ◽  
Yogeshwer Shukla
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Positive Control ◽  
Vehicle Group ◽  
Control Group ◽  
Mouse Bone Marrow ◽  
Human Beings ◽  
Swiss Albino Mice ◽  
Albino Mice ◽  
Marrow Cells

Glyphosate (N-(phosphonomethyl) glycine,C3H8NO5P), a herbicide, used to control unwanted annual and perennial plants all over the world. Nevertheless, occupational and environmental exposure to pesticides can pose a threat to nontarget species including human beings. Therefore, in the present study, genotoxic effects of the herbicide glyphosate were analyzed by measuring chromosomal aberrations (CAs) and micronuclei (MN) in bone marrow cells of Swiss albino mice. A single dose of glyphosate was given intraperitoneally (i.p) to the animals at a concentration of 25 and 50 mg/kg b.wt. Animals of positive control group were injectedi.p. benzo(a)pyrene (100 mg/kg b.wt., once only), whereas, animals of control (vehicle) group were injectedi.p. dimethyl sulfoxide (0.2mL). Animals from all the groups were sacrificed at sampling times of 24, 48, and 72 hours and their bone marrow was analyzed for cytogenetic and chromosomal damage. Glyphosate treatment significantly increases CAs and MN induction at both treatments and time compared with the vehicle control (P<.05). The cytotoxic effects of glyphosate were also evident, as observed by significant decrease in mitotic index (MI). The present results indicate that glyphosate is clastogenic and cytotoxic to mouse bone marrow.

scholarly journals Anticlastogenic effect of vitamin C on cisplatin in vivo

1999 ◽  
Vol 22 (3) ◽  
pp. 415-417 ◽  
Author(s):  
Lusânia M. Greggi Antunes ◽  
Joana D.C. Darin ◽  
Maria de Lourdes P. Bianchi
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Vitamin C ◽  
Wistar Rats ◽  
Bone Marrow Cells ◽  
Chemotherapeutic Agent ◽  
Anticlastogenic Effect ◽  
Rat Bone ◽  
Marrow Cells

The ability of vitamin C (VC) to protect against the clastogenic action of the chemotherapeutic agent cisplatin (DDP, cis-diamminedichloroplatinun II) in rat bone marrow cells was evaluated. DDP was administered to Wistar rats either alone or after treatment with VC. The rats were treated with VC (50, 100 or 200 mg/kg body weight) by gavage 10 min before the administration of DDP (5 mg/kg body weight, ip) and then sacrificed 24 h after treatment. VC significantly reduced (by about 70%) the clastogenicity of DDP in rat bone marrow cells. The antioxidant action of VC presumably modulates the clastogenic action of DDP.

scholarly journals THE RELATION OF CHROMATIN TO HEMOGLOBIN AND BILIRUBIN

1929 ◽  
Vol 49 (6) ◽  
pp. 937-943 ◽  
Author(s):  
Herman H. Riecker
Keyword(s):  
Bone Marrow ◽  
Iron Content ◽  
Bone Marrow Cells ◽  
The Body ◽  
Bile Pigment ◽  
Hemoglobin Production ◽  
Marrow Cells

1. Attention is directed to the diversity of opinion among investigators regarding the site and manner of hemoglobin formation in the body and its relation to bile pigment metabolism. 2. It is probable that in forming new hypotheses on this subject the earlier work of A. B. Macallum on the relation of chromatin to hemoglobin formation has not received sufficient consideration. 3. It has been shown by means of microchemical iron stains of the bone marrow cells, that the iron content of the hematoblast is increased during rapid hemoglobin production in simple anemia. 4. This fact is compatible with the work of Macallum who believed that hemoglobin is derived from the chromatin of the hematoblast. It does not support a theory that hemoglobin is formed as a part of a circulating pigment. 5. It is suggested that bilirubin is derived from the chromatin of body cells through the intermediary stages of the respiratory pigments, hemoglobin and cytochrome, from erythrocytes and other cells, respectively.

scholarly journals Protective role of chlorogenic acid on DNA damage caused by ochratoxin A exposure

2020 ◽  
Vol 40 (2) ◽  
pp. 049
Author(s):  
Noelia Anahí Campra ◽  
Laura Noelia Cariddi ◽  
Franco Matias Escobar ◽  
María Carola Sabini ◽  
Celio Geraldo Freire-de-Lima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Chlorogenic Acid ◽  
Ochratoxin A ◽  
Bone Marrow Cells ◽  
Oral Treatment ◽  
Treated Group ◽  
The Body ◽  
Feed Consumption ◽  
Marrow Cells

Chlorogenic acid (ChlA) has shown short-term protective effects against the cyto-genotoxic effects of ochratoxin A (OTA). The present study evaluated the effect of oral administration of ChlA in male Wistar rats exposed to OTA. OTA (0.4 mg/kg bw/day), ChlA (5 mg/kg bw/day), or the combination of both, were administered orally to animals during 28 days. No deaths, decrease in feed consumption or change in the body weight of animals were observed in any group. In the OTA-treated group a decrease in locomotion as well as increased DNA damage in blood, kidney and bone marrow cells were observed. ChlA alone was not genotoxic for animals. The combination of OTA+ChlA decreased the DNA damage by 37% in blood cells, by 55% in kidney cells and by 80% in bone marrow cells compared to OTA-treated group. In conclusion, oral treatment with ChlA showed a good protective effect on genotoxicity produced by OTA in rats during 28 days exposure.

scholarly journals The combination of lipopolysaccharide and D-galactosamine administration show positive genotoxic effect in mice liver

2020 ◽  
Author(s):  
Wenjing Dong ◽  
Erqun Song ◽  
Yang Song
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Bone Marrow Cells ◽  
Histopathological Examination ◽  
Chronic Administration ◽  
Positive Control ◽  
Genotoxic Effect ◽  
Acute Administration ◽  
Scge Assay ◽  
Marrow Cells

AbstractLipopolysaccharide (LPS)/D-galactosamine (D-GalN) co-administration induced acute liver injury (ALI) and hepatic fibrosis have been extensively studied. However, whether LPS/D-GalN show genotoxic effect is current unknown. Male mice were divided into eight groups and each group contain eight animals. For the acute administration of LPS/D-GalN, the mice were given a single intraperitoneal (i.p.) injection of LPS/D-GalN (25 μg/kg + 250 mg/kg, 25 μg/kg + 500 mg/kg, 50 μg/kg + 500 mg/kg body weight) for 6 h, respectively. The chronic administration was conduct by the i.p. injection of LPS/D-GalN (10 μg/kg + 100 mg/kg) every other day for 8 weeks. Saline solution (0.9%) and cyclophosphamide (CTX) (50 mg/kg body weight) injection were used as negative and positive control, respectively. Using single cell gel electrophoresis (SCGE) assay, we found that the acute administration of LPS/D-GalN induces severe DNA damage in mice hepatic cells, but not in brain, sperm and bone marrow cells, implied the genotoxicity of LPS/D-GalN. Interestingly, the chronic treatment of LPS/D-GalN causes significant genotoxic effect in both hepatic and brain cells, but not sperm and bone marrow cells. Histopathological examination in liver and brain section consistent with SCGE results, accordingly. Our study, for the first time, reported the genotoxic potential of LPS/D-GalN co-administration. In addition, LPS/D-GalN administration may serve as an experimental model for further genotoxic study.

Development of a Myeloproliferative Disease or a T Cell Lymphoblastic Leukemia in a Murine Bone Marrow Transplant Model of NUP214-ABL1.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 618-618
Author(s):  
Jennifer L. Rocnik ◽  
Melanie Cornejo ◽  
Benjamin H. Lee ◽  
Rachel Okabe ◽  
Elizabeth McDowell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Bone Marrow Cells ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Leukemic Cells ◽  
Histopathological Analysis ◽  
Myeloproliferative Disease ◽  
Marrow Cells

Abstract Leukemias are often associated with aberrant tyrosine kinase activity that occurs as a result of chromosomal translocations. These mutations are able to confer a proliferative and survival advantage to leukemic cells, as well as cooperate with other mutations that impair cell differentiation, thus leading to the development of leukemia. NUP214-ABL1 is one such recently identified fusion gene that is generated by episomal amplification. The presence of the fusion was recently identified in approximately 6% of patients with T-cell acute lymphoblastic leukemia (T-ALL). By the use of a murine retroviral bone marrow transplantation model we have demonstrated that mice transplanted with NUP214-ABL1 transduced bone marrow cells developed either a myeloproliferative disorder (MPD) with a disease latency of 70 to 118 days or a T cell lymphoblastic leukemia with a disease latency of 115 to 124 days. The myeloproliferative phenotype was characterized by splenomagaly and leukocytosis, and analysis of the histopathology revealed extramedullary hematopoiesis in the liver, lung, kidney and Peyer’s patches, and an increase of peripheral blood neutrophils. Flow cytometry of single cell suspensions from spleen and bone marrow samples of mice with a myeloproliferative phenotype demonstrated an increase of Gr-1+/Mac-1+ cells (approximately 70%). Two of the mice that were transplanted with NUP214-ABL1 transduced bone marrow cells developed T cell lymphomas that were characterized by large thymomas, a phenotype that is consistent with other models of activated tyrosine kinases over long disease latencies. Histopathological analysis of the thymi revealed effacement of normal thymic architecture as well as T cell infiltrate into the surrounding skeletal muscle. In addition, flow cytometric analysis revealed a significant increase in the CD4+/CD8+ T cell population in the thymi of these animals. No disease was observed in secondary transplant recipients following 60 days of observation. In conclusion, these results indicate that NUP214-ABL1 is able to cause either a myeloproliferative disease or a T cell lymphoma over longer latencies in mice, the latter being similar to the phenotype observed in humans with expression of the NUP214-ABL1 fusion. These findings provide a useful model for future experiments to determine if there is a contribution of other mutations together with the NUP214-ABL1 fusion towards the development of a T-ALL phenotype in mice.

scholarly journals The Effect of the Amount of Isologous Bone Marrow Injected on the Recovery of Hematopoietic Organs, Survival and Body Weight after Lethal Irradiation Injury in Mice

Blood ◽  
1957 ◽  
Vol 12 (3) ◽  
pp. 251-260 ◽  
Author(s):  
PAUL URSO ◽  
C. C. CONGDON
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Leukocyte Count ◽  
Peripheral Blood Leukocyte ◽  
Spleen Weight ◽  
Optimum Response ◽  
Blood Leukocyte ◽  
The Right ◽  
Number Of Cells ◽  
Marrow Cells

Abstract The relation between the amount of isologous bone marrow injected into a lethally irradiated mouse and its 30 day survival, its bone marrow response, the histology of the bone marrow in its left femur, its peripheral blood leukocyte count, the weight of its thymus, spleen, and body, and its appearance showed that quicker recovery of these end points occurred with increasing amounts of bone marrow administered. The bone marrow parameter was the quickest to respond to the varying amounts of bone marrow injected. In addition, no optimum dose of bone marrow was found in these experiments for this end point. This indicates that the bone marrow of an irradiated mouse could be made to show even quicker return to normal by injection of greater amounts of cells. The peripheral blood leukocyte count and the spleen weight also showed very quick recovery with the massive doses of bone marrow injected. For both end points, however, an optimum response was reached, which in the leukocytes, was 64.4 x 106 -237.9 x 106 cells injected, and in the spleen weight, 12.8 x 106 -237.9 x 106. An optimum response for thymus weight was also found with bone marrow doses of 64.4 x 106 - 237.9 x 106 cells. The cell dose for the optimum response in recovery of body weight was 12.8 x 106 - 237.9 x 106. Optimum 30 day survival was reached with injection of 64.4 x 106 bone marrow cells in these experiments. However, doses from 12.8 x 106 to 64.4 x 106 cells were not tested. The dose of bone marrow cells that was calculated to give 50 per cent 30-day survival was 0.42 x 106 (0.17 x 106, 1.92 x 106) cells for the males and 1.06 x 106 (0.42 x 106, 2.51 x 106) cells for the females. The calculated dose of bone marrow cells that would give 1 per cent 30-day survival of the males was 0.008 x 106 (0.0008 x 106, 0.0284 x 106) and for the females 0.0102 x 106 (0.001 x 106, 0.040 x 106) cells. These point estimates seem to be unreliable in view of the extremely large 95% confidence intervals. However, in experiments done by other workers at the National Cancer Institute similar to those reported in this paper, M. Schneiderman determined a threshold dose ranging from 0.0026 to 0.0320 x 106 cells by a somewhat different analysis of the data.7 Jacobson et al. cite a figure of 3-5 x 106 bone marrow cells from young donor mice as causing 53% 28-day survival in CF No. 1 mice exposed to 900 r.2 In using bone marrow from older mice, they found that 5-9.9 x 106 cells caused 54.9% 28-day survival. They also estimate that 50,000 cells are necessary to produce significant recovery of mice after an LD99 exposure. This figure is similar to that determined from the results of the present experiments. The results obtained from mice injected intravenously with a massive dose of bone marrow 3 days after irradiation indicated that the number of cells in the bone marrow of the right femur can be elevated within a few hours after injection. However, this could be observed only in an irradiated animal where the number of cells in the right femoral bone marrow was already low. A similar observation was made by Graevsky.8 This finding gives further support to the hypothesis that intravenously injected bone marrow transplants to bone marrow sites in the irradiated host.9

scholarly journals Olive oil protects against chromosomal aberrations induced by doxorubicin in wistar rat bone marrow cells

1999 ◽  
Vol 22 (2) ◽  
pp. 223-227 ◽  
Author(s):  
Lusânia Maria Greggi Antunes ◽  
Catarina Satie Takahashi
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Olive Oil ◽  
Chromosomal Aberrations ◽  
Antitumor Agents ◽  
Bone Marrow Cells ◽  
Wistar Rat ◽  
Free Radical Scavengers ◽  
Rat Bone ◽  
Marrow Cells

There is considerable interest in identifying dietary compounds which have the capacity to protect against chromosomal aberrations induced by antitumor agents. Fatty acids and their constituents are able to act as free radical scavengers. Doxorubicin (DXR) is an important chemotherapeutic agent, that also induces chromosome aberrations. Rat bone marrow cells treated simultaneously with olive oil (10 ml/kg body weight) and DXR (90 mg/kg body weight) developed significantly fewer chromosomal aberrations and abnormal metaphases than those treated with DXR alone.

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