scholarly journals Antimutagenic activity and hepatoprotective effect of anti-radiation drugs

Author(s):  
Л.П. Сычева ◽  
Л.М. Рождественский ◽  
Н.И. Лисина ◽  
Т.Г. Шлякова ◽  
В.В. Зорин

Изучена антимутагенная активность противолучевых препаратов разного механизма действия: беталейкина, флагеллина, индралина и рибоксина в краткосрочных и хроническом экспериментах на мышах in vivo. Все препараты проявили антимутагенные свойства в клетках костного мозга, а также гепатопротекторное действие. Наибольший эффект при используемых условиях эксперимента отмечен для беталейкина и нового противолучевого препарата флагеллина. The antimutagenic activity of anti-radiation drugs betaleukin, flagellin, indraline and riboxin with different mechanisms of action was studied in short-term and chronic experiments in mice in vivo. All drugs showed antimutagenic properties in bone marrow cells, as well as hepatoprotective effect. The greatest effect under the used experimental conditions was noted for betaleukin and the new anti-radiation drug flagellin.

2007 ◽  
Vol 292 (6) ◽  
pp. H2582-H2588 ◽  
Author(s):  
Masayuki Kubo ◽  
Tao-Sheng Li ◽  
Ryo Suzuki ◽  
Mako Ohshima ◽  
Shu-Lan Qin ◽  
...  

Therapeutic angiogenesis can be induced by the implantation of bone marrow cells (BMCs). Hydrogen peroxide (H2O2) has been shown to increase VEGF expression and to be involved in angiogenesis. We tested the hypothesis that pretreatment with H2O2 enhances the efficacy of BMCs for neovascularization. H2O2 pretreatment was done by incubating mouse BMCs in 5 μM H2O2 for 30 min, followed by washing twice with PBS. The H2O2-pretreated and untreated BMCs were then studied in vitro and in vivo. RT-PCR analysis showed that expression of VEGF and Flk-1 mRNA was significantly higher in H2O2-pretreated BMCs than in untreated BMCs after 12 and 24 h of culture ( P < 0.01). Pretreatment with H2O2 also effectively enhanced the VEGF production and endothelial differentiation from BMCs after 1 and 7 days of culture ( P < 0.05). To estimate the angiogenic potency in vivo, H2O2-pretreated or untreated BMCs were intramuscularly implanted into the ischemic hindlimbs of mice. After 14 days of treatment, many of the H2O2-pretreated BMCs were viable, showed endothelial differentiation, and were incorporated in microvessels. Conversely, the survival and incorporation of the untreated BMCs were relatively poor. Microvessel density and blood flow in the ischemic hindlimbs were significantly greater in the mice implanted with H2O2-pretreated BMCs than in those implanted with untreated BMCs ( P < 0.05). These results show that the short-term pretreatment of BMCs with low-dose H2O2 is a novel, simple, and feasible method of enhancing their angiogenic potency.


Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4054-4063 ◽  
Author(s):  
Benjamin J. Frisch ◽  
Rebecca L. Porter ◽  
Benjamin J. Gigliotti ◽  
Adam J. Olm-Shipman ◽  
Jonathan M. Weber ◽  
...  

Abstract Microenvironmental signals can determine hematopoietic stem cell (HSC) fate choices both directly and through stimulation of niche cells. In the bone marrow, prostaglandin E2 (PGE2) is known to affect both osteoblasts and osteoclasts, whereas in vitro it expands HSCs and affects differentiation of hematopoietic progenitors. We hypothesized that in vivo PGE2 treatment could expand HSCs through effects on both HSCs and their microenvironment. PGE2-treated mice had significantly decreased number of bone trabeculae, suggesting disruption of their microarchitecture. In addition, in vivo PGE2 increased lineage− Sca-1+ c-kit+ bone marrow cells without inhibiting their differentiation. However, detailed immunophenotyping demonstrated a PGE2-dependent increase in short-term HSCs/multipotent progenitors (ST-HSCs/MPPs) only. Bone marrow cells transplanted from PGE2 versus vehicle-treated donors had superior lymphomyeloid reconstitution, which ceased by 16 weeks, also suggesting that ST-HSCs were preferentially expanded. This was confirmed by serial transplantation studies. Thus in vivo PGE2 treatment, probably through a combination of direct and microenvironmental actions, preferentially expands ST-HSCs in the absence of marrow injury, with no negative impact on hematopoietic progenitors or long-term HSCs. These novel effects of PGE2 could be exploited clinically to increase donor ST-HSCs, which are highly proliferative and could accelerate hematopoietic recovery after stem cell transplantation.


Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4136-4142 ◽  
Author(s):  
I Kawashima ◽  
ED Zanjani ◽  
G Almaida-Porada ◽  
AW Flake ◽  
H Zeng ◽  
...  

Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34+ cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34+ Kit-, CD34+ Kit(low), and CD34+ Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34+ Kit(low) cells showed signs of engraftment according to analysis of CD45+ cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34+ Kit(high) cells and two fetuses receiving CD34+ Kit- cells failed to show evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34+ Kit(low) cells exhibited signs of engraftment upon serial examination. Earlier in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population.


1984 ◽  
Vol 26 (2) ◽  
pp. 152-157
Author(s):  
S. M. Singh ◽  
D. L. Reimer

Frequency of sister chromatid exchanges (SCE) were recorded separately for different chromosomes from bone marrow cells of female mice of the two genetic strains (C3H/S and C57BL/6J). SCEs were evaluated following different doses of 5-bromo-2′deoxyuridine (BrdU) as nine hourly i.p. injections. The SCE per cell increased with increasing BrdU doses which was slightly higher in C3H/S than in the C57BL/6J. SCEs per cell were variable at every treatment – strain combination, possibly reflecting the heterogeneous nature of the bone marrow cells. In general, there is a positive correlation between SCE per chromosome and the relative chromosome length. Total SCEs on one of the large chromosomes (most likely the X chromosome), however, are significantly higher than expected on the basis of relative length alone. Most of this increase is attributable to one of the homologues of this chromosome, which is not in synchrony with the rest of the chromosomes and may represent the late-replicating X. These results when viewed in the light of replication properties of the heterochromatinized X, suggest a direct involvement of DNA replication in SCE formation and may argue against the replication point as the sole site for the SCEs.Key words: sister chromatid exchange, BrdU, recombination, replication, X chromosome.


Blood ◽  
2013 ◽  
Vol 121 (12) ◽  
pp. e90-e97 ◽  
Author(s):  
Mark Wunderlich ◽  
Benjamin Mizukawa ◽  
Fu-Sheng Chou ◽  
Christina Sexton ◽  
Mahesh Shrestha ◽  
...  

Key Points A relevant xenograft chemotherapy model was developed by using standard AML induction therapy drugs and primary human AML patient samples. Human AML cells show significantly increased sensitivity to in vivo chemotherapy treatment compared with murine LSK and total bone marrow cells.


Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1633-1640
Author(s):  
LM Pelus ◽  
PS Gentile

Intravenous (IV) injection of 0.1 to 10 micrograms of authentic prostaglandin E2 (PGE2) in intact steady-state mice induces a population of bone marrow and spleen cells having the capacity to suppress CFU-GM proliferation when admixed with normal bone marrow cells. Equivalent suppression of CFU-GM committed to monocytic as well as granulocytic differentiation was observed using colony-stimulating factors (CSFs) differing in their lineage specificities and by direct morphological analysis of proliferating clones. Kinetic analysis indicates that suppressive bone marrow cells appear within 2 hours after PGE2 injection, are maximal at 6 hours, and are no longer observed by 24 hours postinjection. Positive and negative selection studies using monoclonal antibodies indicate that the PGE2-induced suppressor cells react positively with anti-GMA 1.2, MAC1, and F4/80 monoclonal antibodies, suggesting a myeloid/monocytic origin. As few as 1,000 positively selected bone marrow or spleen cells were able to inhibit maximally normal CFU-GM proliferation by 50,000 control bone marrow cells. Suppression of normal CFU-GM can be substituted for by 24- hour cell-free supernates from unseparated bone marrow cells or GMA 1.2 or F4/80 positively selected marrow or spleen cells from PGE2-treated but not control mice. These supernates also inhibited BFU-E proliferation. Injection of as few as 2 million bone marrow cells from PGE2-treated mice into steady-state mice or animals hematopoietically rebounding following a sublethal injection of cyclophosphamide significantly suppressed total CFU-GM proliferation in recipient mice within 6 hours. In summary, these studies describe the detection of a novel hematopoietic control network induced by PGE2 in intact mice.


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