scholarly journals Genotoxicity Assessment and Protective Effect of Anogeissus leiocarpus Roots against Cyclophosphamide-Induced DNA Damage In Vivo

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Aku Enam Motto ◽  
Povi Lawson-Evi ◽  
Aboudoulatif Diallo ◽  
Kwashie Eklu-Gadegbeku
Keyword(s):  
Bone Marrow ◽  
Protective Effect ◽  
Bone Marrow Cells ◽  
Micronucleus Test ◽  
Marrow Cell ◽  
Dependent Manner ◽  
Polychromatic Erythrocytes ◽  
Anogeissus Leiocarpus ◽  
Marrow Cells

Background. Belonging to the family of Combretaceae, the roots of Anogeissus leiocarpus are traditionally used to treat diabetes, wounds, infections, pain, and gastrointestinal diseases. To our knowledge, no genotoxicity assessment of the plant was reported. Hence, this study was designed to evaluate the potential genotoxic and protective effects of extract of Anogeissus leiocarpus roots using the micronucleus test on mice bone marrow cells in vivo. Methods. Three different concentrations (250, 500, and 1000 mg·kg−1) of hydroalcoholic extract of roots of A. leiocarpus were administered daily for 7 days per os to mice, and the genotoxicity was induced by the administration ip of cyclophosphamide. Genotoxicity and cytotoxicity were evaluated by counting, respectively, the number of micronucleated polychromatic erythrocytes and polychromatic erythrocytes to total erythrocytes in the bone marrow of mice. Results. The administration of A. leiocarpus did neither increase the ratio of the polychromatic erythrocyte (PCE) nor the frequency of micronucleated PCE (MNPCE) significantly in the bone marrow cells of the mice, compared to the vehicle control animals. However, a significant increase in the incidence of MNPCE in the bone marrow cell of the cyclophosphamide-treated mice was found. Moreover, in the groups treated with the total extract of A. leiocarpus at different doses plus cyclophosphamide, there was a significant decrease p < 0.0001 in MNPCEs compared to the positive controls, in a dose-dependent manner. Conclusion. This first finding reports that the extract of A. leiocarpus was neither genotoxic nor cytotoxic. However, it shows a protective effect against the genotoxicity and cytotoxicity induced by cyclophosphamide.

Genotoxic Effect of Epirubicin in Mouse Bone Marrow in vivo

2010 ◽  
Vol 65 (3-4) ◽  
pp. 211-217 ◽  
Author(s):  
Asuman K. Sen ◽  
Emin Karakas ◽  
Rahmi Bilaloglu
Keyword(s):  
Bone Marrow ◽  
Anticancer Drug ◽  
Bone Marrow Cells ◽  
Micronucleus Test ◽  
Negative Control ◽  
Genotoxic Effect ◽  
Mouse Bone Marrow ◽  
Polychromatic Erythrocytes ◽  
Marrow Cells

The genotoxic effect of epirubicin, a semisynthetic anthracycline antibiotic which has been used as an anticancer drug, was investigated in vivo on bone marrow cells of Swiss albino mice using the micronucleus test. To determine the incidence of micronuclei, mice were injected intraperitoneally with the drug at single doses of 4, 6, 8, and 10 mg/kg body weight. Then, bone marrow was sampled 18, 24, 36, and 48 h after the treatment. Polychromatic and normochromatic erythrocytes were examined for the presence of micronuclei. Epirubicin significantly increased the frequency of micronucleated polychromatic erythrocytes (MNPCEs) for all treatment periods compared with the negative control (P < 0.001). The frequency of MNPCEs increased with the dose, but at the highest dose used (which is considered to be quite toxic), the frequency of MNPCEs was rather lower. Epirubicin also decreased the ratio of polychromatic to normochromatic erythrocytes (PCE/NCE) for all sampling intervals, which is indicative of bone marrow cytotoxicity. It can be concluded from the present study that the anticancer drug epirubicin has genotoxic effects on mouse bone marrow cells.

scholarly journals CD34+ human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4136-4142 ◽  
Author(s):  
I Kawashima ◽  
ED Zanjani ◽  
G Almaida-Porada ◽  
AW Flake ◽  
H Zeng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
In Utero ◽  
Fetal Sheep ◽  
Hematopoietic Stem ◽  
Show Evidence ◽  
Marrow Cells

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.

scholarly journals Observations on the binding and interaction of radioiodinated colony- stimulating factor with murine bone marrow cells in vivo

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 408-420 ◽  
Author(s):  
G Pigoli ◽  
A Waheed ◽  
RK Shadduck
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Cell Interaction ◽  
Peritoneal Macrophages ◽  
Colony Stimulating Factor ◽  
Murine Bone Marrow ◽  
Stimulating Factor ◽  
Marrow Cells

Abstract Radioiodinated L-cell-derived colony-stimulating factor (CSF) was used to characterize the binding reaction to murine bone marrow cells. The major increment in cell-associated radioactivity occurred over 24 hr incubation at 37 degrees C, but virtually no binding was observed at 4 degrees C. The reaction was saturable with approximately 1 ng/ml of purified CSF. Unlabeled CSF prevented the binding, whereas a number of other hormones and proteins did not compete for CSF uptake. Further specificity studies showed virtually no binding to human bone marrow, which is unresponsive to this form of murine CSF. Minimal CSF uptake was noted with murine peritoneal macrophages, but virtually no binding was detected with thymic, lymph node, liver, or kidney cells. The marrow cell interaction with tracer appeared to require a new protein synthesis, as the binding was prevented by cycloheximide or puromycin. Preincubation of marrow cells in medium devoid of CSF increased the degree of binding after 1 hr exposure to the tracer. This suggests that CSF binding sites may be occupied or perhaps decreased in response to ambient levels of CSF in vivo. Approximately 70% of the bound radioactivity was detected in the cytoplasm at 24 hr. This material was partially degraded as judged by a decrease in molecular weight from approximately 62,000 to 2 peaks of approximately 32,000 and approximately 49,000, but 72% of the binding activity was retained. After plateau binding was achieved, greater than 80% of the radioactivity released into the medium was degraded into biologically inactive peptides with molecular weights less than 10,000. These findings suggest that the interaction of CSF with marrow cells is characterized by binding with subsequent internalization and metabolic degradation into portions of the molecule that are devoid of biologic activity.

Dynamic Patterns of Migration and Expansion of Hematopoiesis during MGMT Mediated Drug Selection.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 156-156 ◽  
Author(s):  
Yuan Lin ◽  
Perrin Cheung ◽  
David L. Wilson ◽  
Stanton L. Gerson
Keyword(s):  
Bone Marrow ◽  
In Vivo Imaging ◽  
Bone Marrow Cells ◽  
Clonal Expansion ◽  
Dependent Manner ◽  
Drug Selection ◽  
Hematopoietic Stem ◽  
Mouth Disease Virus ◽  
Marrow Cells

Abstract While hematopoietic engraftment kinetics are well appreciated after lethal irradiation in the mouse, most observations have been limited to blood samples or terminal examination of marrow or spleen. The development of non-invasive bioluminescence in vivo imaging technology allows a dynamic picture of engraftment and clonal expansion to be defined. We have extended this technology to the process of drug resistance gene therapy. We hypothesized that drug selection would profoundly affect the extent and dynamics of hematopoietic stem cells (HSC) engraftment and clonal expansion after lentiviral mediated gene transfer of the P140KMGMT gene into murine HSC. In previous studies, we have shown that P140KMGMT gene containing retroviral and lentiviral transduced bone marrow cells provided significant protection against chemotherapeutic drugs BCNU and TMZ given with BG (O6-Benzylguanine), in vitro and in vivo. We generated a bicistronic lentiviral vector containing P140KMGMT gene and firefly luciferase gene linked by 2A sequence of FMDV(Foot-and-Mouth Disease Virus), which will cleave itself during ribosomal translation. Whole bone marrow cells was collected from BALB/c mice 4 days after 5-FU treatment and transduced with P140KMGMT-luc lentiviruses at MOI of 1.4. Transduced bone marrow cells were transplanted into lethally irradiated or non-myeloablated syngeneic recipient mice at different cell numbers. Initial bioluminescent signal emerged 6–8 days after transplantation in both lethally irradiated and non-myeloablated recipients. The onset of bioluminescent foci after transplantation occurred in a cell dose dependent manner. The initial signal emitted predominantly from bone marrow, especially femurs, humeri and vertebrae during the early stage of clonal expansion. Intense signal appeared in spleen at days 12–14 and became weaker or even disappeared by days 20–28. Clonal expansion and engraftment greatly increased after a single course of BG+TMZ treatment and initiated strong hematopoiesis in non-myeloablated recipients. Total body bioluminescence intensity of drug treated mice increased 24 fold and 7 fold compared to non-treated mice in both non-myeloablated and lethally irradiated recipients, respectively. A transient phase suggesting migration through the lymphatic system and in the spleen occurred in most mice and was exacerbated by drug selection, but this was less clear in lethally irradiated mice, where engraftment was more confined to the marrow spaces. Bioluminescence in vivo imaging reveals active migration between the bone marrow and the spleen during hematopoiesis. Drug selection has a significant impact on the patterns of engraftment and clonal expansion of HSC and progenitor cells after transplantation.

scholarly journals In vivo genotoxicity of treated water containing the cylindrospermopsin-producer Cylindrospermopsis raciborskii

2014 ◽  
Vol 12 (3) ◽  
pp. 474-483 ◽  
Author(s):  
A. L. Fonseca ◽  
J. Da Silva ◽  
E. A. Nunes ◽  
S. M. F. O. Azevedo ◽  
R. M. Soares
Keyword(s):  
Bone Marrow ◽  
Comet Assay ◽  
Bone Marrow Cells ◽  
Micronucleus Test ◽  
Liver Cells ◽  
Cylindrospermopsis Raciborskii ◽  
Producer Strain ◽  
Treated Water ◽  
Marrow Cells

Cylindrospermopsin (CYN) is an alkaloid commonly produced by some cyanobacteria that has been implicated in outbreaks of human illness. The aim of this study was to investigate the genotoxicity of Cylindrospermopsis raciborskii cellular content (including CYN) and its byproducts resulting from chlorination during water treatment. DNA damage in blood and liver cells was analysed by the comet assay and micronucleus test (MN). Mice were injected intraperitoneally with the following treatments: (a) physiological saline, (b) treated water, (c) treated water plus C. raciborskii extract (CYN producer strain, CYPO-011 K), (d) C. raciborskii extract (CYN producer strain, CYPO-011 K), (e) C. raciborskii extract (CYN non producer strain), and (f) treated water plus C. raciborskii extract (CYN non producer strain) extract. After 48 h, samples were taken to perform tests (blood and liver cells to the comet assay and bone marrow to MN test). The CYPO-011 K had a genotoxic and mutagenic effects on liver and bone marrow cells. The group that received chlorine-treated water plus CYPO-011 K also exhibited genotoxic effects in the liver, as well as in the blood, and a mutagenic effect in blood marrow cells. The results emphasise the need of improving CYN monitoring in waters bodies in order to reduce the risk of human exposure.

scholarly journals Evaluation of the mutagenic effect of the iodinated contrast medium Urografina® 292 using the micronucleus test in mouse bone marrow cells

2013 ◽  
Vol 85 (2) ◽  
pp. 737-744 ◽  
Author(s):  
MONICA B.B. BELLE ◽  
DANIELA D. LEFFA ◽  
DALIANE MAZZORANA ◽  
VANESSA M. DE ANDRADE
Keyword(s):  
Bone Marrow ◽  
Contrast Media ◽  
Contrast Medium ◽  
Bone Marrow Cells ◽  
Micronucleus Test ◽  
Control Group ◽  
Mouse Bone Marrow ◽  
Iodinated Contrast ◽  
Polychromatic Erythrocytes ◽  
Marrow Cells

Contrast media (CM) are frequently used in diagnostic radiology and in radiotherapy as a diagnostic tool and in treatment planning. Previous studies have demonstrated that these compounds induce chromosomal aberrations. This study evaluates the mutagenic effects induced by the contrast medium Urografina® 292 (meglumine amidotrizoate and sodium-ionic dimmer) in bone marrow cells (BMC) of mice in vivo. Micronuclei assay was performed in BMC of CF-1 mice injected with CM 1.5 and 3.0 mL/kg intravenous doses and 1.0, 2.0, 3.0 mL/kg intraperitoneal doses. The animals were beheaded 24 h after treatment by cervical dislocation, and femur BMC from each animal were used in the micronucleus test. The group treated with the highest intravenous injection of Urografina® 292 (3.0 mL/kg) presented an increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in relation at the control group (P<0.05). The results obtained after intraperitoneal administration of CM showed that all doses (1.0 mL/kg, 2.0 mL/kg and 3.0 mL/kg) increased the frequency of MNPCEs, being significantly different from the negative control (P< 0.01). The present results suggest that iodinated contrast media Urografina® 292 may cause a significant increase of cytogenetic damage in bone marrow cells of mice.

scholarly journals EVALUTING THE ABILITY OF PLEUROTUS OSTREATUS AQUEOUS EXTRACT TO MODULATE GENOTOXICITY INDUCED BY CYCLOPHOSPHAMIDE IN MICE BONE MARROW CELLS

2020 ◽  
Vol 51 (5) ◽  
pp. 1405-1412
Author(s):  
Farhan & Chechan
Keyword(s):  
Bone Marrow ◽  
Pleurotus Ostreatus ◽  
Bone Marrow Cells ◽  
Mutagenic Effect ◽  
Concomitant Treatment ◽  
Murine Bone Marrow ◽  
Polychromatic Erythrocytes ◽  
Experimental Protocols ◽  
Marrow Cells

This study was aimed to evaluate the ability of local oyster mushroom(Pleurotus ostreatus; ID: MF065715.1; cultivated until maturation in growth medium containing cumin extract) to modulate the genotoxicity induced by cyclophosphamide (CP) in bone marrow cells of mice. In vivo genotoxicity was assessed by quantifying the incidence of micronucleated polychromatic erythrocytes in the bone marrow cells of mice that were administered different doses of P.ostreatus extract (150, 200,250, and 300 mg/kg/day( respectively, individually, and in combination with CP (40 mg/kg body weight) according to the following three experimental protocols (pre 2h, post 2h, and concomitant treatment for 14 days, respectively). Analysis and microscopic examination of micronuclei (MN) revealed no mutagenic effect of P.ostreatus extract alone at all the doses evaluated. By contrast, CP administration significantly increased (P<0.05) incidence of MN. Importantly, the co-administration of P.ostreatus extract with CP caused a significant and dose-dependent reduction in MN induced by CP in the murine bone marrow cells. These data suggest that P.ostreatus extract administration has a protective effect against genotoxic damage inflicted by CP. The dietary cumin may serve as a scavenger for free radicals generated by CP and may augment the antioxidant activity of P. ostreatus extract. These findings open up new avenues for the use of oyster mushrooms in many applications, including pharmacological preparations and food supplements.

scholarly journals ESBLs (Extended Spectrum beta Lactamase) DDSM: (Double Disc Synergy Method) NCCL: (National Committee for Clinical Laboratory Standards

2019 ◽  
Vol 24 (7) ◽  
pp. 33
Author(s):  
WAGDI SABEEH SADEQ ◽  
SHIREEN ABED AL-RAZAQ TAHA
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Micronucleus Test ◽  
Negative Control ◽  
Toxic Effects ◽  
National Committee ◽  
Alcohol Extract ◽  
Polychromatic Erythrocytes ◽  
Mean Differences ◽  
Marrow Cells

Genotoxicity and cytotoxicity of Belomycin (BLM) have been evaluated in bone-marroww cells by micronucleus test, as well as the analysis of sperm shape abnormalities in male white mice, considering that BLM is the most wide anticancer drug used with patients. Also, the study includes assessment the effect of crude water and alcoholic extracts of the four o'clock flowers (Mirabilis jalapa Linn) in reducing BLM toxicity and the study was carried out  in the Genetics Laboratory of the Department of biology for the period from 1-10-2017 to 1-5-2019.So the genotoxicity and cytotoxicity were evaluated independently and in conjunction between two different dosages of BLM 0.8 and 1.6 mg.kg-1.bwt. and three orally dosage of different concentration of crud extracts, which is 39.8, 26.52, 13.26 mg.kg-1 and 7.02, 4.68, 2.34 mg.kg-1 o water and alcohol extract respectively. The results of assessment of BLM genotoxic effects showed that the drug caused induction of micronuclei, here were significant increase in micronucleated polychromatic erythrocytes (MNIPCEs) and significant increase in micronuclei(MNI) in the groups treated with 0.8 and 1.6 mg.kg-1 of BLM, compare to negative control at the level of significance P <0.05 On the other hand, the results showed that BLM has potential to induce sperm shape abnormalities, which include head and tail abnormalities, It included an increase in the proportion of morphological abnormalities in the head and tail of the sperm when compared to negative control at the significant level of P <0.05. The results also showed, that treatment with low dosages of four o'clock flower crud extracts didn’t induce neither micronuclei or any increase in PCEs numbers nor sperm shape abnormalities, although some toxic effects do exist with the higher dosages. Evaluation of results from dependent treatments of BLM and different concentrations of water and alcoholic crud extracts, we observed significant role of these extracts in reducing toxic effects of the drug BLM in bone marrow cells, which caused significant decrease in mean differences of MNIPCEs and MNI. More over the results showed significant decrease in mean differences of sperm shape and tail abnormalities compared to negative control. Results of the current study suggest that water and alcoholic four o'clock flower crud extracts have a role in reducing genotoxic and cytotoxic effects of BLM in bone-marrow cells and sperms of white mice   http://dx.doi.org/10.25130/tjps.24.2019.126

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