An evaluation of the genotoxic and cytotoxic effects of the anti-obesity drugs sibutramine and fenproporex

2010 ◽  
Vol 29 (3) ◽  
pp. 187-197 ◽  
Author(s):  
Cristiano José da Silva ◽  
José Ernesto dos Santos ◽  
Catarina Satie Takahashi
Keyword(s):  
Bone Marrow ◽  
Micronucleus Test ◽  
Chronic Illnesses ◽  
Cytotoxic Activities ◽  
Obese People ◽  
Cytotoxic Effects ◽  
Swiss Mice ◽  
Polychromatic Erythrocytes ◽  
Therapeutic Alternatives ◽  
Obesity Drugs

Anti-obesity medications deserve special considerations at the present time due to an increasing number of overweight and obese people who require these therapeutic alternatives. Obesity is positively associated with several chronic illnesses, including cancer. In this work, we evaluated the possible genotoxic and/or cytotoxic actions of two drugs, sibutramine and fenproporex, in the doses of 10, 20 and 40 mg/kg body weight (bw), administered intraperitoneally in male Swiss mice. The genotoxic effect was analyzed by comet assay and micronucleus test. We found that both drugs increased the frequency of genotoxic damage in Swiss mice, but did not present cytotoxic activities towards the polychromatic erythrocytes of the bone marrow of these animals.

scholarly journals Evaluation of (anti)genotoxic activities of Phyllanthus niruri L. in rat bone marrow using the micronucleus test

2013 ◽  
Vol 49 (1) ◽  
pp. 135-148 ◽  
Author(s):  
Fernando Márlisson de Queiroz ◽  
Kayo Wanderson de Oliveira Matias ◽  
Mylena Mylana Freire da Cunha ◽  
Aline Schwarz
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Weight Gain ◽  
Micronucleus Test ◽  
Body Weight Gain ◽  
Tap Water ◽  
Control Group ◽  
Cytotoxic Activities ◽  
Phyllanthus Niruri ◽  
Polychromatic Erythrocytes

Phyllanthus niruri L. (Euphorbiaceae), known as "quebra-pedra" (Portuguese for "stonebreaker"), is an herb used for kidney disorders. In light of its frequent use by the population, the present study aimed to investigate the genotoxic, antigenotoxic and cytotoxic activities of a standardized P. niruri extract in bone marrow rats. Three groups of 12 animals were treated daily by gavage over a period of 30 days, with 50, 150 or 250 mg/kg of P. niruri extract aqueous solution. The control group (n = 12) received tap water. At the end of treatment (day 31), groups were divided into two minor subgroups (n=6/group) and received cyclophosphamide (50 mg/kg, i.p.) or saline 0.9% (i.p.). After 24 hours, we evaluated the frequency of micronucleated polychromatic erythrocytes for each animal (MNPCE) at 1000 PCE. Cytotoxicity was evaluated with the PCE/NCE ratio (NEC = normochromatic erythrocytes). General toxicity was assessed during treatment using the parameters of body weight gain, ration and water consumption. The dry extract did not provoke changes in body weight, weight gain, ration and water intake or changes in the frequency of MNPCE or cytotoxicity in bone marrow. We propose that the P. niruri extract used here showed no genotoxic, antigenotoxic and cytotoxic activities under the experimental conditions.

scholarly journals Study of the correlation between blood cholinesterases activity, urinary dialkyl phosphates, and the frequency of micronucleated polychromatic erythrocytes in rats exposed to disulfoton

2013 ◽  
Vol 49 (1) ◽  
pp. 149-154 ◽  
Author(s):  
Mariane Gonçalves Santos ◽  
Ricardo Vilela Vitor ◽  
Maurício Gustavo Nakamura ◽  
Luana de Souza Morelini ◽  
Rafaela Scalco Ferreira ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Pesticide Exposure ◽  
Micronucleus Test ◽  
Urinary Metabolites ◽  
Chromosomal Damage ◽  
Polychromatic Erythrocytes ◽  
Induce Mutagenesis ◽  
Diethyl Dithiophosphate ◽  
Bone Marrow Micronucleus

Organophosphates (OPs) are widely used as pesticides, and its urinary metabolites as well as the blood cholinesterases (ChEs) activity have been reported as possible biomarkers for the assessment of this pesticide exposure. Moreover, the OPs can induce mutagenesis, and the bone marrow micronucleus test is an efficient way to assess this chromosomal damage. This paper reports a study carried out to verify the correlation among the disulfoton exposure, blood ChEs activity, urinary diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP), as well as micronucleated polychromatic erythrocytes (MNPCEs) frequency. Four groups of rats (n=12) were exposed to disulfoton at 0, 2.8, 4.7, and 6.6 mg kg-1 body weight. The blood ChEs activity, urinary DETP and DEDTP concentrations, and MNPCEs frequency were determined. It was observed that the plasmatic and erythrocytary ChEs activity decreased from 2.9% to 0.5% and from 35.9 to 3.3%, respectively, when the disulfoton dose was increased from 0 to 6.6 mg kg-1 (correlation of 0.99). Urinary DETP and DEDTP concentrations, as well as the MNPCEs frequency, increased from 0 to 6.58 µg mL-1, from 0 to 0.04 µg mL-1, and from 0 to 1.4%, respectively, when the disulfoton dose was increased from 0 to 6.58 mg kg-1 body weight.

scholarly journals Cytotoxic and Genotoxic Evaluation of the Aqueous and Hydroalcoholic Leaf and Bark Extracts of Crataegus oxyacantha in Murine Model

Plants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2217
Author(s):  
Fany Renata Aguilera-Rodríguez ◽  
Ana Lourdes Zamora-Perez ◽  
Clara Luz Galván-Moreno ◽  
Rosalinda Gutiérrez-Hernández ◽  
Claudia Araceli Reyes Estrada ◽  
...  
Keyword(s):  
Murine Model ◽  
Leaf Extract ◽  
Micronucleus Test ◽  
Genotoxic Effects ◽  
Cytotoxic Effects ◽  
Blood Smears ◽  
Polychromatic Erythrocytes ◽  
Aqueous Leaf Extract ◽  
Peripheral Blood Smears ◽  
Sampling Times

Crataegus oxyacantha has been mainly used in traditional medicine for the treatment of cardiovascular diseases. However, its safety profile has not been fully established, since only the genotoxic effects of C. oxyacantha fruit have been described. Therefore, the objective of this work was evaluating the cytotoxicity and genotoxicity of the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha by means of the micronucleus test in a murine model. Doses of 2000, 1000, and 500 mg/kg of both extracts were administered orally for 5 days in mice of the Balb-C strain. Peripheral blood smears were performed at 0, 24, 48, 72, and 96 h after each administration. The number of polychromatic erythrocytes (PCEs), micronucleated polychromatic erythrocytes (MNPCEs), and micronucleated erythrocytes (MNEs) was determined at the different sampling times. Our results showed that the leaf and bark of C. oxyacantha increase the number of MNEs at the 2000 mg/kg dose, and only the aqueous leaf extract decreases the number of PCEs at the same dose. Therefore, the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha showed genotoxic effects, and only the aqueous leaf extract exhibited cytotoxic effects.

scholarly journals Genotoxic evaluation of ceftriaxone by in vivo micronucleus test in albino mice

2018 ◽  
Vol 7 (9) ◽  
pp. 1705
Author(s):  
Kunjumon Dayana ◽  
Megaravalli R. Manasa
Keyword(s):  
Bone Marrow ◽  
Micronucleus Test ◽  
Micronucleus Assay ◽  
Generation Cephalosporin ◽  
New Drugs ◽  
Control Group ◽  
Genotoxic Potential ◽  
Polychromatic Erythrocytes ◽  
Albino Mice

Background: Genotoxicity screening of drugs is essential. It is mandatory for new drugs. However, screening of drugs already in use is also necessary. Several cephalosporins are reported to induce chromosomal aberrations in previous studies. But there is paucity of data regarding the genotoxic potential of ceftriaxone. Hence the present study was undertaken to evaluate the genotoxic potential of ceftriaxone, a third generation cephalosporin, by micronucleus assay in albino mice.Methods: In vivo micronucleus test was performed with mice bone marrow after intraperitoneal injection of ceftriaxone at 100mg/kg BW and 200mg/kg BW at 24 hr and 48 hr harvest time. Mice bone marrow was harvested, and slides were prepared. The percentage of micronucleated polychromatic erythrocytes (% MnPCE) and the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PCE:NCE) were determined. The data from ceftriaxone treated groups was compared with control group and analyzed using ANOVA followed by Dunnett's test.Results: Ceftriaxone at the dose of 100mg/kg BW and 200mg/kg BW did not exhibit any significant increase in the percentage of micronucleated polychromatic erythrocytes. It also did not decrease the ratio of polychromatic erythrocytes to normochromatic erythrocytes significantly.Conclusions: The present study demonstrates that ceftriaxone is not genotoxic in in vivo micronucleus study in albino mice at a dose of 100mg/kg BW and 200mg/kg BW.

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 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

scholarly journals Assessment of mutagenicity and cytotoxicity of Solanum paniculatum L. extracts using in vivo micronucleus test in mice

2010 ◽  
Vol 70 (3) ◽  
pp. 601-606 ◽  
Author(s):  
PM. Vieira ◽  
SC. Santos ◽  
L. Chen-Chen
Keyword(s):  
Bone Marrow ◽  
Micronucleus Test ◽  
Folk Medicine ◽  
Mutagenic Effect ◽  
Mouse Bone Marrow ◽  
Cytotoxic Effects ◽  
Tropical America ◽  
Higher Doses ◽  
Ethanolic Leaf Extract

Solanum paniculatum L. is a plant species widespread throughout tropical America, especially in the Brazilian Savanna region. It is used in Brazil for culinary purposes and in folk medicine to treat liver and gastric dysfunctions, as well as hangovers. Because of the wide use of this plant as a therapeutic resource and food, the present study aimed at evaluating the mutagenic and cytotoxic effects of S. paniculatum ethanolic leaf and fruit extracts using the mouse bone marrow micronucleus test. Our results indicate that neither S. paniculatum ethanolic leaf extract nor its ethanolic fruit extract exhibited mutagenic effect in mice bone marrow; however, at higher doses, both extracts presented cytotoxic activity.

scholarly journals Cytogenetic evaluation of α, β-amirina obtained in resin of Protium heptaphylum (Aubl.) Marchand in polychromatics erythrocytes of mice swiss.

2021 ◽  
Vol 9 (4) ◽  
pp. 10-21
Author(s):  
Lucas Rodrigues do Rego ◽  
Everton Pantoja Vale ◽  
Danilo Dheyvison Nascimento Pureza ◽  
Moacir de Azevedo Bentes Monteiro Neto ◽  
Fernando Antônio de Medeiros ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Medicinal Plants ◽  
Peripheral Blood ◽  
Micronucleus Test ◽  
Amazon Rainforest ◽  
Swiss Mice ◽  
Caudal Vein ◽  
The Future ◽  
Low Toxicity ◽  
Cytogenetic Profile

The Amazon Rainforest has a great variety of medicinal plants, among them we can highlight the “Almecegueira” or “Breu Branco” (Protium heptaphylum) in Portuguese, the producer of a greenish-white resin that hardens when it touches the air, known by its gastroprotective and anti-inflammatory effects. These effects are attributed to a triterpene mixture of α and β amirine, predominant in the resin. The purpose of the study is to obtain a cytogenetic profile to the α, β-amirine mixture obtained in the resin of P. heptaphylum. For this, the micronucleus test was used in peripheral blood and bone marrow; administering solution in Swiss mice with the dosages of 1mg/Kg, 3mg/Kg, and 10mg/Kg, diluted in 5% DMSO, the effects were observed in 24h and 48h after the treatment. For the test in peripheral blood the mice’s caudal vein was punctured, while for the bone marrow test, the femurs of the animals were obtained from which bone marrow samples were taken. It was found that in peripheral blood, the administration of the compounds did not cause genotoxicity in 24h and 48h, in contrast, antigenotoxicity was, for concentrations 1; 3 and 10mg/kg, respectively 10%; 12%; 67% in 24h and 9%; 15%; 73% in 48h.  In the bone marrow, no genotoxicity was observed, as for antigenotoxicity was observed that for concentrations 1; 3 e 10mg/kg the percentage of reduction was respectively: 11%, 15%, and 30% in 24h and 13% 16% 33% in 48h. It is concluded that the studied compound can be an alternative for treatments in the future since it presents low toxicity and high antigenotoxic potential.

scholarly journals Evaluation of the Genotoxic and Antigenotoxic Effects of Andiroba (Carapa guianensis Aublet) Oil and Nanoemulsion on Swiss Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Karina Motta Melo ◽  
Maria Luiza Fascineli ◽  
Susana Suely Rodrigues Milhomem-Paixão ◽  
Cesar Koppe Grisolia ◽  
Alberdan Silva Santos ◽  
...  
Keyword(s):  
Comet Assay ◽  
Protective Effect ◽  
Micronucleus Test ◽  
Tween 80 ◽  
The Other ◽  
Carapa Guianensis ◽  
Swiss Mice ◽  
Polychromatic Erythrocytes ◽  
Span 80 ◽  
Antigenotoxic Effects

The Carapa guianensis (andiroba) oil is commonly used by the Amazon population for medicinal purposes. The objective of this study was to determine the genotoxic and antigenotoxic potential of the andiroba oil (AO) and nanoemulsion (AN) using Swiss mice. Therefore, we used the comet assay and micronucleus test. The AO predominant compounds were oleic (39.13%), palmitic (33.22%), and linoleic (16.86%) acids. AN composition obeyed the surfactant/oil ratio of 0.69, and the Tween 80/Span 80 ratio was held at 0.9. Our results showed no cytotoxicity or genotoxicity in the mice treated with AO and AN alone. However, there was a significant reduction in the polychromatic erythrocytes (PCEs) numbers in all groups treated with doxorubicin (DOX), including those pretreated with AO and AN. Thus, the samples tested did not protect against DOX. On the other hand, our results showed a large increase in micronucleus (MN) formation when the mice were treated with DOX alone; these numbers were reduced when the animals were pretreated with AO and AN. The results indicate a protective effect of andiroba on MN formation and show no evidence of genotoxicity in mice.

Toxicology of Diethylene Glycol Butyl Ether 3. Genotoxicity Evaluation in an In Vitro Gene Mutation Assay and an In Vivo Cytogenetic Test

1993 ◽  
Vol 12 (2) ◽  
pp. 155-159 ◽  
Author(s):  
B. Bhaskar Gollapudi ◽  
V. A. Linscombe ◽  
M. L. Mcclintock ◽  
A. K. Sinha ◽  
C. R. Stack
Keyword(s):  
Bone Marrow ◽  
Gene Mutation ◽  
Micronucleus Test ◽  
Mouse Bone Marrow ◽  
Butyl Ether ◽  
Polychromatic Erythrocytes ◽  
Mutation Assay ◽  
Gene Mutation Assay

DGBE was evaluated in a forward gene mutation assay at the HGPRT locus of CHO cells in culture and in an in vivo mouse bone marrow micronucleus test for cytogenetic damage. DGBE did not elicit a positive response in the CHO/HGPRT assay when tested up to a maximum concentration of 5000 μg/ml with and without an external metabolic activation system (S-9). In the micronucleus test employing three post-treatment bone marrow sampling times (24, 48, and 72 hr), DGBE was ineffective in increasing the incidence of micronucleated polychromatic erythrocytes (MN-PCE) when tested in both sexes up to a maximum tolerated dose of 3300 mg/kg body weight. Thus, these data and those of others indicate a general lack of genotoxic potential for DGBE in short-term tests.

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