scholarly journals Protective effects of rosmarinic acid against radiation-induced damage to the hematopoietic system in mice

2016 ◽  
Vol 57 (4) ◽  
pp. 356-362 ◽  
Author(s):  
Wenqing Xu ◽  
Fujun Yang ◽  
Yujie Zhang ◽  
Xiu Shen

Abstract Rosmarinic acid (RA) is an ester of caffeic acid and 3, 4-dihydroxyphenyl lactic acid. It is a potent antioxidant that functions by scavenging free radicals. Here, we used a 30-day survival assay to investigate the radioprotective effects of RA. Mice were treated with RA once per day for 10 consecutive days starting at 3 days before gamma irradiation at 7.5 Gy until 7 days post irradiation. Mice treated with 100 and 200 mg/kg body weight (bw) of RA had 30-day survival rates of 89% and 72%, respectively, compared with 32% in the control group, and the differences were statistically significant ( P = 0.0008 and 0.0421, respectively). Spleen colony–forming units (CFU-S), the number of nucleated cells in the bone marrow (BMNC), bone marrow DNA content, and hematological parameters of the peripheral blood were measured to investigate the radioprotective effect of RA on the hematopoietic system. The treatment groups that received RA at 50, 100 and 150 mg/kg bw and whole-body exposure to 5.5 Gy of 137 Cs γ- radiation had significantly higher CFU-S, BMNC and DNA content than the irradiation-only group. Assessment of hematological parameters in the peripheral blood showed that the treatment groups receiving RA at doses of 50, 100 and 150 mg/kg bw had higher white blood cell counts, hemoglobin and platelets than the radiation-only group. These results suggested that the administration of RA promoted the recovery of peripheral blood cells in irradiated mice.

2019 ◽  
Vol 38 (10) ◽  
pp. 1195-1211
Author(s):  
S Bala ◽  
NA Chugh ◽  
SC Bansal ◽  
A Koul

The present study was premeditated to examine the radioprotective effects of aqueous Aloe vera gel extract against whole-body X-ray irradiation–induced hematological alterations and splenic tissue injury in mice. Healthy male balb/c mice were divided into four groups: group 1, control; group 2, A. vera (50 mg/kg body weight) administered per oral on alternate days for 30 days (15 times); group 3, X-ray exposure of 2 Gy (0.25 Gy twice a day for four consecutive days in the last week of the experimental protocol); and group 4, A. vera + X-ray. X-ray exposure caused alterations in histoarchitecture of spleen along with enhanced clastogenic damage as assessed by micronucleus formation and apoptotic index. Irradiation caused an elevation in proinflammatory cytokines like tumor necrosis factor and interleukin-6, total leucocyte counts, neutrophil counts and decreased platelet counts along with unaltered red blood cell counts and hemoglobin. Irradiation also caused an elevation in reactive oxygen species (ROS), lipid peroxidation (LPO) levels, lactate dehydrogenase activity and alterations in enzymatic and nonenzymatic antioxidant defense mechanism in plasma and spleen. However, administration of A. vera gel extract ameliorated X-ray irradiation–induced elevation in ROS/LPO levels, histopathological and clastogenic damage. It also modulated biochemical indices, inflammatory markers, and hematological parameters. These results collectively indicated that the A. vera gel extract offers protection against whole-body X-ray exposure by virtue of its antioxidant, anti-inflammatory and anti-apoptotic potential.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2372-2372 ◽  
Author(s):  
Peter Dean Emanuel ◽  
Zhuo Wang ◽  
Danying Cai ◽  
Mary R. Stofega ◽  
James G. Keck ◽  
...  

Abstract TLK199 is a novel glutathione analog that is a selective inhibitor of the enzyme glutathione S-transferase (GST) P1-1. TLK199 treatment induces hematopoietic cell proliferation and differentiation through activation of the MAP kinase signaling pathway leading to activation of JNK and ERK2. In rodent models of chemotherapy induced neutropenia, treatment with TLK199 accelerated recovery of white cell counts at rates comparable to treatment with G-CSF. We now report TLK199 treatment of myeloid progenitor cells isolated from normal human blood resulted in the increased formation of CFU-GM (46%) CFU-MK (47%) and BFU-E (142%) lineages over baseline. A corresponding increase in the percentage of cells expressing CD11b, a granulocyte and monocyte marker, was observed in the CFU-GM cells. Since TLK199 is currently being evaluated in a Phase 2a trial in patients with refractory MDS, we examined the effect of treatment on formation of BFU-E, CFU-GM and CFU-GEMM before and after TLK199 treatment at doses of 50 to 400 mg/m2. A significant increase in the number of hematopoietic progenitor cell colonies measured from patient peripheral blood and bone marrow was observed as early as Day 4 of Cycle 1 as compared to pretreatment baseline. Ten of 12 patients showed an increase in at least one colony forming type (BFU-E, CFU-GM and CFU-GEMM) and 7 of 12 had an increase in all three colony forming types following TLK199 administration. These results correlate with clinical improvement in hematological parameters in peripheral blood and bone marrow observed in MDS patients treated with TLK199. Studies are underway to define the mechanism of bone marrow and peripheral blood count recovery observed following treatment of MDS patients with TLK199 and the role of GST P1-1 as a regulatory element in myeloid proliferation and differentiation.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yixuan Liu ◽  
Suhong Xie ◽  
Lei Li ◽  
Yanhui Si ◽  
Weiwei Zhang ◽  
...  

Abstract Background This study investigates the effect of autologous bone marrow transfusion (BMT) on the reconstruction of both bone marrow and the immune system in patients with AIDS-related lymphoma (ARL). Methods A total of 32 patients with ARL participated in this study. Among them, 16 participants were treated with conventional surgery and chemotherapy (control group) and the remaining 16 patients were treated with chemotherapy followed by autologous bone marrow transfusion via a mesenteric vein (8 patients, ABM-MVI group) or a peripheral vein (8 patients, ABM-PI group). Subsequently, peripheral blood and lymphocyte data subsets were detected and documented in all patients. Results Before chemotherapy, no significant difference in indicators was observed between three groups of ARL patients. Unexpectedly, 2 weeks after the end of 6 courses of chemotherapy, the ABM-MVI group, and the ABM-PI group yielded an increased level of CD8+T lymphocytes, white blood cells (WBC), and platelet (PLT) in peripheral blood in comparison to the control group. Notably, the number of CD4+T lymphocytes in the ABM-PI group was significantly higher than that in the other two groups. Additionally, no significant difference in haemoglobin levels was observed before and after chemotherapy in both the ABM-MVI and ABM-PI groups, while haemoglobin levels in the control group decreased significantly following chemotherapy. Conclusions Autologous bone marrow transfusion after chemotherapy can promote the reconstruction of both bone marrow and the immune system. There was no significant difference in bone marrow recovery and reconstruction between the mesenteric vein transfusion group and the peripheral vein transfusion group.


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Alaa Marzouk

Introduction: The journey from single cell to complex being is attributable to stem cells role. Adult stem cells originate during ontogeny & persist in specialized niches within organs. Asymmetric division of each stem cell during differentiation produces : one daughter stem cell & one daughter transit amplifying/intermediate cell having migratory properties. Forced migration of hematopoietic stem/progenitor cells (HSPC) from bone marrow into peripheral blood is called mobilization. Accumulating evidence suggests that attenuation of the chemokine stromal derived factor-1(SDF-1)-CXCR4 axis that plays a pivotal role in retention of HSPC in bone marrow (BM) results in the release of these cells from the BM into peripheral blood. Recently, adult cells have been genetically reprogrammed to an embryonic stem cell like state. Induced pluripotent stem cells (IPSCs) were similar to human embryonic stem cells in morphology, proliferative capacity, expression of cell surface antigens, & gene expression. Treatment of ischemic vascular disease of lower limbs remains a significant challenge. Unfortunately, if medical & surgical salvage procedures fail, amputation is an unavoidable result for those patients. Aim of Work: (Hypothesis) To assess the application of implantation of autologous stem/progenitor cell in the treatment of chronic limb ischemia & to evaluate the safety, efficacy & feasibility of this novel therapeutic approach. Methods: A total of 24 patients with chronic limb ischemia not eligible for arterial reconstruction or endovascular procedures were enrolled & randomized (1:1) to either the implanted group or the control group. Control group: Conventional medical therapy in the form of anti platelet therapy & vasodilators. Implanted group: Subcutaneous injection of 300μ g/day of recombinant human granulocyte colony stimulating factor (G-CSF) for 5 days to mobilize stem/progenitor cells from BM. Total leucocytic count is measured daily to follow up successful mobilization of bone marrow mononuclear cells (BMMNCs). Stem cell Harvesting After 5 days peripheral blood mononuclear cells (PBMNCs) were harvested using a cell separator. Samples from apheresis products are subjected to TLC measurement & immunophenotypic characterization of CD34+ cells by flow cytometry. The collected PBMNCs were implanted by multiple intramuscular injections into ischemic limbs. Results: There was significant increase in pain free walking distance & ankle/brachial index (ABI) & significant decreased rest pain. Effectiveness was documented by : reduced number of amputation, increase ABI & improvement of the quality of life in therapeutic group compared to control group. Conclusion: The novel therapeutic approach of PBMNCs implantation in patients with chronic limb ischemia is safe, feasible & effective in decreasing co-morbidity & rate of amputation. Safety was manifested by absence of complications during G-CSF therapy or during harvesting & injection of the stem cells. Recommendations: 1- Future studies on larger number of patients & longer follow up. 2- Controlled studies using different methods & different cell population (PBMNCs, BMMNCs or MSCs) to compare the outcome of each. 3-Studing the role of endothelial progenitor cell dysfunction in different ischemic diseases to develop successful gene therapy.


2021 ◽  
Author(s):  
Cong Wang ◽  
Xiaohang Qin ◽  
Guanzhong Gong ◽  
Lizhen Wang ◽  
Ya Su ◽  
...  

Abstract Objectives: To quantify the pelvic bone marrow (PBM) fat content changes receiving different radiation doses of concurrent chemoradiotherapy for cervical cancer and to determine association with peripheral blood cell counts. Methods: Fifty-four patients were prospectively collected. Patients underwent MRI iterative decomposition of water and fat with echo asymmetrical and least squares estimation (IDEAL IQ) scanning at RT-Pre, RT mid-point, RT end, and six months. The changes in proton density fat fraction (PDFF%) at 5–10 Gy, 10–15 Gy, 15–20 Gy, 20–30 Gy, 30–40 Gy, 40–50 Gy, and >50 Gy doses were analyzed. Spearman’s rank correlations were performed between peripheral blood cell counts versus the differences in PDFF% at different dose gradients before and after treatment. Results: The lymphocytes (ALC) nadirs appeared at the midpoint of radiotherapy, which was only 27.6% of RT-Pre; the white blood cells (WBC), neutrophils (ANC), and platelets (PLT) nadirs appeared at the end of radiotherapy which was 52.4%, 65.1%, and 69.3% of RT-Pre, respectively. At RT mid-point and RT-end, PDFF% increased by 46.8% and 58.5%, respectively. Six months after radiotherapy, PDFF% decreased by 4.71% under 5–30 Gy compared to RT-end; while it still increased by 55.95% compared to RT-Pre. There was a significant positive correlation between PDFF% and ANC nadirs at 5–10 Gy (r = 0.62, P = 0.006), and correlation was observed between PDFF% and ALC nadirs at 5–10 Gy (r = 0.554, P = 0.017). Conclusion: MRI IDEAL IQ imaging was a non-invasive approach to evaluate and track the changes of PBM fat content with concurrent chemoradiotherapy for cervical cancer. The limitation of low-dose bone marrow irradiation volume in cervical cancer concurrent chemoradiotherapy should be paid more attention.


Medicina ◽  
2007 ◽  
Vol 43 (1) ◽  
pp. 60 ◽  
Author(s):  
Vilma Jurkštienė ◽  
Anatolijus Kondrotas ◽  
Egidijus Kėvelaitis

The aim of the study was to investigate the immunostimulatory properties of bigroot geranium. Material and methods. Possible nonspecific characteristics of bigroot geranium were evaluated by the total leukocyte count in the peripheral blood, and qualitative changes of blood were assessed using Shilling’s formula by evaluating changes in lymphocyte counts. In addition, we also studied changes in the counts of Tcell precursors in the thymus and B lymphocytes in the spleen. Ethanol extract of the leaves of bigroot geranium was produced at the Department of Food Technology, Kaunas University of Technology. Studies were performed on mice Bl 57 (n=21). The control group (n=7) received distilled water at a dose of 1 mL/day. The second and third groups received 1% and 10% extract of bigroot geranium, respectively, as a food supplement. Changes in cell counts were investigated after 4 weeks following the initiation of the trial. Results. After a 4-week administration of 1% extract of bigroot geranium (1 mL/day) (mice group, n=7), leukocyte count in the peripheral blood increased to 6.1×109 cells/L, and lymphocyte count – to 70%, but changes were not statistically significant. The other case group of mice (n=7) received 10% extract of bigroot geranium for 4 weeks at a dose of 1 mL/day. In this group, leukocyte count in the peripheral blood increased statistically significantly from 4.4×109 cells/L to 7.2×109 cells/L (p<0.01), and lymphocyte percentage – from 52% to 80% (p<0.001), as compared to control. Thymocyte (T lymphocytes) counts in thymus and splenocyte (B lymphocytes) counts in the spleen showed a tendency to increase after the administration of 1% and 10% extracts. After a 4-week administration of 1% extract of bigroot geranium, thymocyte and splenocyte counts increased from 0.342×106 cells to 0.372×106 cells per mg of tissue and from 0.395×106 cells to 0.405×106 cells per mg of tissue, respectively, as compared to control group (p>0.1). After the administration of 10% extract of bigroot geranium, thymocyte count increased to 0.488×106 cells per mg of tissue (p<0.01), and splenocyte count – to 0.504×106 cells per mg of tissue (p<0.01). Conclusion. The extracts of the leaves of bigroot geranium increased leukocyte count and lymphocyte percentage in the peripheral blood, and after a 4-week administration of 10% extract of bigroot geranium, a statistically significant increase in the counts of T lymphocytes (in the thymus) and B lymphocytes (in the spleen) was observed. The immunostimulatory effect depends on the dose of the extract.


Blood ◽  
1968 ◽  
Vol 32 (4) ◽  
pp. 662-667 ◽  
Author(s):  
R. STORB ◽  
R. B. EPSTEIN ◽  
E. D. THOMAS

Abstract Ten dogs were exposed to 1200 r. of whole body irradiation at a dose rate of 9.2 r./min. Five of these dogs were then given infusions of 21 to 74 x 109 autologous peripheral blood cells which had been previously stored at -80 C. 4.0 to 19.4 x 109 of these cells were lymphocytes, 0.4 to 4.9 x 109 were monocytes and 16.4 to 50.3 x 109 were granulocytes. All five dogs showed clinical or histologic evidence of bone marrow repopulation. The remaining 5 dogs were given 7 to 22 x 109 autologous thoracic duct lymphocytes. In none of these dogs was marrow repopulation observed. It was concluded that hemopoietic stem cells are not present in the thoracic duct lymph of the dog in any appreciable number.


1985 ◽  
Vol 34 (4) ◽  
pp. 407-416 ◽  
Author(s):  
Yukio OGAWA ◽  
Kiyoshi MATSUMOTO ◽  
Eiichi KAMATA ◽  
Yasukazu IKEDA ◽  
Toyozo KANEKO

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4781-4781
Author(s):  
Jacek Rolinski ◽  
Agnieszka Bojarska-Junak ◽  
Iwona Hus ◽  
Anna Dmoszynska

Abstract TNF has been proposed to play a role in the regulation of growth and death of leukemic B-CLL cells. However, the biological effects of TNF on leukemic cells, as well as its role as a prognostic factor need to be further investigated. The aim of the study was to eevaluate the correlation of TNF and its receptors in peripheral blood (PB) and bone marrow (BM) with the stage of B-CLL and some other clinical parameters. PB and BM were taken from 44 newly diagnosed, untreated B-CLL. patients. The control group consisted of 20 healthy subjects. We used flow cytometry technique to assess the capability of T and B lymphocytes to produce TNF and ELISA method to measure plasma levels of TNF and their soluble receptors. We found, that PB and BM plasma TNF concentration in the patients was significantly higher than in the healthy control (2.61 pg/ml. vs 0.62 pg/ml; and 2.91 pg/ml vs 0.75 pg/ml, respectively p<0.001). TNF concentration in PB and BM was significantly higher in Rai stage III–IV than in early stages (p<0.01). There was a correlation between the PB and BM TNF level and lymphocytosis (p<0.005) and the total tumor mass (TTM) (p<0.0001). The PB and BM TNF concentration positively correlated with the percentage of T CD3+ lymphocytes producing intracellular TNF (p<0.01). The percentage of T cells from PB an BM expressing cytoplasmic TNF was significantly higher in patients (PB:39.11±16.97%; BM:40.73±18.19%) than in normal controls (PB:15.74±7.95%; BM:18.80±12.93%) (p< 0.00001; p<0.005, respectively). In PB and BM from B-CLL patients the percentage of CD3+ cells expressing intracellular TNF was significantly higher than the percentage of CD19+/TNF+ cells (p<0.0001). Besides, it was found that the percentage of T cells expressing cytoplasmic TNF positively correlated with the stage of disease (p<0.01). In PB positive correlation were found between the number of T CD3+/TNF+ cells and lymphocytosis (p<0.05) and TTM (p<0.001). The percentage of leukaemic B cells positive for TNF did not correlate with the stage of disease. There was increased expression of TNF-RI and TNF-RII in leukaemic B cells in comparison to normal B-cells was observed (p<0.0001). We found positive correlation between the number of CD5+ B lymphocytes and the levels of soluble TNF-RII (sTNF-RII) (p< 0.05). The sTNF-RII levels in PB and BM significantly correlated with the stage of disease acc. Rai (p<0.0001). Furthermore, the sTNF-RII concentration positively correlated with lymphocytosis and TTM (p<0.0001). These results strongly support the key role TNF in B-CLL pathogenesis. Our results suggest that TNF may function as growth factor for B-CLL cells. CD3+T cells may be the important source of this cytokine in advanced B-CLL. It seems that changes in T cells capability to produce cytoplasmic TNF are associated with disease progression. However, further studies are required to confirm the key role of TNF in B-CLL pathogenesis.


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