scholarly journals Assessment of Anti-Cytogenotoxic Effects of Quercetin in Animals Treated with Topotecan

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Saleh A. Bakheet

The present investigation was directed to study the possible chemoprotective activity of orally administered quercetin against topotecan-induced cyto- and genotoxicity towards mouse somatic cellsin vivo. DNA strand breaks, micronuclei formation, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Oxidative stress markers such as intracellular reactive oxygen species generation, lipid peroxidation, and reduced and oxidized glutathione were assessed in bone marrow as a possible mechanism underlying this amelioration. Quercetin was neither cytotoxic nor genotoxic in mice at doses tested. Pretreatment of mice with quercetin significantly reduced topotecan-induced genotoxicity and cytotoxicity in bone marrow cells, and these effects were dose dependent. Moreover, prior administration of quercetin ahead of topotecan challenge ameliorated oxidative stress markers. In conclusion, quercetin has a protective role in the abatement of topotecan-induced cyto- and genotoxicity in the bone marrow cells of mice that resides, at least in part, on its antioxidant effects. Based on the data presented, strategies can be developed to decrease the topotecan-induced bone marrow suppression and secondary malignancy in cancer patients and medical personnel exposing to topotecan.

Drug Research ◽  
2021 ◽  
Author(s):  
Nazira Fatima ◽  
Muhammad Saleem ◽  
Umar Shahbaz

Abstract Aim of study This study investigated whether pre-activated bone marrow cells with sodium nitro prusside have effectiveness in the inhibition of diabetic wound healing in diabetic rabbits. In diabetic skin disorders and conditions involved redox state disturbances. The aim was to determine the effect of two minimum dosages of sodium nitro prusside, and its’ potential with bone marrow cells for chronic wound healing in-vivo. Methods Full-thickness skin dorsal wounds were created on diabetic rabbits. The effects of two minimum concentrations of sodium nitro prusside solution with bone marrow cells on wound healing were studied. The useful combination of sodium nitro prusside with bone marrow cells on wound repair may be attributed to its functional influences on inflammation, angiogenesis, cell proliferation, matrix deposition, and remodeling. Results The in-vivo experiments confirmed that pre-activated bone marrow cells contributed to wound healing by alleviating oxidative stress, increasing proliferation and migration, decreasing apoptosis. In histological results, improved collagen deposition, enhanced re-epithelization, angiogenesis, and decreased inflammatory infiltration were also detected in wound biopsies. Conclusions For the treatment of chronic wounds, cell-based therapy was an attractive approach. Bone marrow cells have a low ability to differentiate various types of cells or late healing without pretreatment. So it was needed to increase their potency of differentiation. The transplantation of pretreated bone marrow cells with a prime quantity of sodium nitro prusside solution improved chronic wound healing with a greater level of growth factors and a minimum level of oxidative stress.


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.


Blood ◽  
1977 ◽  
Vol 50 (5) ◽  
pp. 857-866
Author(s):  
BJ Torok-Starb ◽  
NS Wolf ◽  
DR Boggs

Cellulose acetate membranes (CAM) placed in the peritoneal cavity of mice develop a macrophage layer capable of supporting in vivo hematopoietic colonies from intraperitoneally injected bone marrow cells. Modifications allowing for routine morphologic identification of colonies showed that both erythrocytic (E) and granulocytic (G) colonies occur with a consistent E:G ratio of 0.19 +/- 0.037. Stimulating recipients by bleeding or phenylhydrazine injection did not produce a significant change in the total number of colonies and a reduction in granulocytic colonies so that the E:G ratio significnatly increased. Hypertransfusion of donor animals had no effect on the number of erythroid colonies that grew on CAM of average recipients. The total colony-forming ability of bone marrow cells from genetically anemic W/WV mice was found not to differ from that of normal +/+ littermates; however, the E:G ratio of W/WV marrow in bled recipients was significantly lower (p less than 0.01) then that of +/+ marrow. These studies suggest that a CAM system supports an erythroid progenitor which is not affected by hypotransfusion of the donor animal, yet is dependent upon erythropoietin for colony formation, and that it is defective in the W/WV mouse.


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