Impact of antidepressant drug clomipramine on hepatorenal functions, lipid peroxidation, micronucleus frequencies and DNA damage using an alkaline comet assay

2013 ◽  
Vol 1 (1) ◽  
pp. 98
Author(s):  
Fatma E. Agha ◽  
Eman R.Youness R.Youness ◽  
Hassanane M. M.
Keyword(s):  
Lipid Peroxidation ◽  
Bone Marrow ◽  
Dna Damage ◽  
Body Weight ◽  
Comet Assay ◽  
Recovery Period ◽  
Antidepressant Drug ◽  
Control Group ◽  
Polychromatic Erythrocytes ◽  
Therapeutic Doses

Clomipramine is a tricyclic antidepressant commonly used to treat anxiety related behavioral disorders in human and animals. The current study was performed to assess the effects of different therapeutic doses of clomipramine hydrochloride supplementation on hepato-renal functions, lipid peroxidation, frequencies of micronucleated polychromatic erythrocytes in bone marrow, DNA damage in peripheral blood lymphocytes using the comet assay and effects of withdrawal of the drug for 4 weeks on these parameters. Forty two Swiss albino male mice were divided into seven equal groups. The first group served as a control, while groups 2, 4 and 6 were orally treated with low (75 mg/kg of body weight), medium ((100 mg/kg of body weight), and high doses (250 mg/kg of body weight), respectively of clomipramine hydrochloride daily for 30 days. However, groups 3, 5 and 7 served as low, medium and high withdrawal groups for 4 weeks. Different therapeutic doses of clomipramine hydrochloride resulted in a significant increase in the levels of serum ALT, AST, BUN and creatinine compared to control. Also, plasma malondialdehyde levels showed were significant increase in mice treated by different therapeutic doses of clomipramine hydrochloride compared to control group. In contrast, the administration of clomipramine hydrochloride in three therapeutic doses for 30 days caused a significant increase in the frequency of micronuclei in polychromatic erythrocytes of mice bone marrow, this increase reached more than ten times the value determined before the treatment and directly proportional to the dose. The level of basal endogenous DNA damage measured as the mean of percentage of DNA in the tail of the lymphocytes in mice treated by low, medium and high therapeutic doses of clomipramine hydrochloride were significantly higher than in controls. However, in the recovery period (4weeks), a significant amelioration in all studied parameters was observed. Results indicated that, clomipramine is a hepato renal toxic drug and induces a significant amount of DNA damage and in-vivo genotoxic drug.

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 The study of primary DNA damage in the bone marrow of mice under the combined action of pesticides

2021 ◽  
Vol 29 (4) ◽  
pp. 14-21
Author(s):  
Nataliya S. Averianova ◽  
Liliya A. Kara ◽  
Olga V. Egorova ◽  
Nataliya A. Ilyushina
Keyword(s):  
Lipid Peroxidation ◽  
Bone Marrow ◽  
Dna Damage ◽  
Comet Assay ◽  
Blood Serum ◽  
Bone Marrow Cells ◽  
Active Ingredients ◽  
Technical Grade ◽  
Combined Action ◽  
Primary Dna Damage

Introduction. The study of the potential negative effects of combinations of several pesticide active ingredients is an important and understudied area of toxicological and hygienic research. The initial phase of the genotoxicant action on the genetic structures in cells is the primary DNA damage, the identification of which makes it possible to assess the early stages of the genotoxic effect of xenobiotics and their mixtures. The DNA comet assay is widely used for these purposes. The aim of the research is to assess the primary DNA damage under the combined action of pesticides. Materials and methods. To assess DNA damage the experiments on CD-1 mice of both sexes were performed using alkaline comet analysis. The concentration of active products reacting with thiobarbituric acid (TBA) in the blood serum of white outbred rats was assessed as a marker of lipid peroxidation. Results. It was found that mixtures of 2,4-D-acid + glyphosate and thiram + carbendazim did not cause the formation of breaks and alkali-labile sites in the DNA of mice bone marrow cells. Exposure to the combination of the technical grade active ingredients captan and fludioxonil induced the breaks and alkali-labile sites in the DNA of animal bone marrow cells. The comparison of the genotoxicity assessment results obtained by the comet assay and results of analysis of the TBA-active product concentrations in the rat blood serum suggests that the observed primary DNA damage upon exposure to the captan and fludioxonil combination can be mediated by the induction of lipid peroxidation and subsequent interaction of the resulting products with nucleic acids. Conclusion. The results indicate that some pesticides in combination can damage hereditary material in mammalian cells. Therefore, in order to ensure the safe use of pesticides for public health it is necessary to take into account the data on the genotoxicity not only of individual pesticide technical grade active ingredients but also their combinations.

Evaluation of genotoxicity of pan masala employing chromosomal aberration and micronucleus assay in bone marrow cells of the mice

2009 ◽  
Vol 25 (7) ◽  
pp. 467-471 ◽  
Author(s):  
BN Mojidra ◽  
K. Archana ◽  
AK Gautam ◽  
Y. Verma ◽  
BC Lakkad ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chromosome Aberration ◽  
Chromosomal Aberration ◽  
Bone Marrow Cells ◽  
Micronucleus Assay ◽  
Control Group ◽  
Genotoxic Potential ◽  
Polychromatic Erythrocytes ◽  
Significant Difference ◽  
Marrow Cells

Pan masala is commonly consumed in south-east Asian and other oriental countries as an alternate of tobacco chewing and smoking. Genotoxic potential of pan masala (pan masala plain and pan masala with tobacco known as gutkha) was evaluated employing chromosome aberration (CA) and micronucleus (MN) assay in vivo. Animals were exposed to three different doses (0.5%, 1.5% and 3%) of pan masala plain (PMP) and gutkha (PMT) through feed for a period of 6 months and micronucleus and chromosomal aberrations were studied in the bone marrow cells. Induction of mean micronuclei in polychromatic erythrocytes (MNPCE) and normochromatic erythrocyte (MNNCE) was higher in both types of pan masala treated groups with respect to control group. Both pan masala plain and gutkha treatment significantly induced the frequency of MNPCE and MNNCE in the bone marrow cells, indicating the genotoxic potential. Furthermore, slight decline in the ratio of polychromatic erythrocytes to normochromatic erythrocytes was also noticed, suggesting the cytotoxic potential even though the ratio was statistically non significant. A dose-dependent, significant increase in chromosome aberration was observed in both types of pan masala treated mice with respect to control. However, no significant difference in micronucleus and chromosomal aberration induction was noticed between two types of pan masala exposed (PMP and PMT) groups. Results suggest that both types of pan masala, i.e. plain and gutkha, have genotoxic potential.

scholarly journals Protection of sperm DNA against oxidative stress in vivo by accessory sex gland secretions in male hamsters

Reproduction ◽  
2002 ◽  
pp. 491-499 ◽  
Author(s):  
H Chen ◽  
MP Cheung ◽  
PH Chow ◽  
AL Cheung ◽  
W Liu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Prostate Gland ◽  
Single Strand ◽  
Ventral Prostate ◽  
Control Group ◽  
Dna Breakage ◽  
Accessory Glands ◽  
Sperm Dna ◽  
Epididymal Spermatozoa

Reactive oxygen species scavengers present in male accessory sex gland secretions might afford antioxidant protection to sperm DNA. This study was conducted to determine whether accessory sex gland secretions protect the genome and function of spermatozoa against oxidative damage in the uterus. Male golden hamsters were divided into four experimental groups: (i) all accessory sex glands removed; (ii) ampullary glands removed; (iii) ventral prostate gland removed and (iv) sham-operated controls. Ejaculated spermatozoa recovered from uteri 15-30 min after mating with experimental males and caput and cauda epididymal spermatozoa obtained from intact males were incubated in 0-20 mmol NADPH l(-1) for 2 h. These spermatozoa and untreated uterine spermatozoa were processed for two types of comet assay (single cell gel electrophoresis): alkaline comet assay (pH > 13) which revealed single-strand DNA breakage and neutral comet assay (pH 9) which revealed double-strand DNA breakage. In comparison with the sham-operated controls, spermatozoa that had not been exposed to accessory sex gland secretions had a higher incidence and more extensive single-strand DNA damage with increasing concentrations of NADPH. Spermatozoa from hamsters without ampullary glands and from hamsters without the ventral prostate glands were similar to those of the control group. After incubation with NADPH, the capacity of spermatozoa from hamsters without accessory glands and from sham-operated controls to fuse with oocytes in vitro was reduced. However, only hamsters without accessory glands showed a negative correlation between single-strand DNA damage and sperm-oocyte fusion. Cauda epididymal spermatozoa were less susceptible to NADPH treatment compared with caput epididymal spermatozoa. The results of the present study showed that male accessory sex gland secretions can preserve the integrity of the sperm genome.

scholarly journals Persistent Increased Frequency of Genomic Instability in Women Diagnosed with Breast Cancer: Before, during, and after Treatments

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Márcia Fernanda Correia Jardim Paz ◽  
André Luiz Pinho Sobral ◽  
Jaqueline Nascimento Picada ◽  
Ivana Grivicich ◽  
Antonio Luiz Gomes Júnior ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Comet Assay ◽  
Peripheral Blood ◽  
Micronucleus Test ◽  
Cancer Control ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Buccal Cells ◽  
Oncological Treatment

This study aimed to evaluate DNA damage in patients with breast cancer before treatment (background) and after chemotherapy (QT) and radiotherapy (RT) treatment using the Comet assay in peripheral blood and the micronucleus test in buccal cells. We also evaluated repair of DNA damage after the end of RT, as well as the response of patient’s cells before treatment with an oxidizing agent (H2O2; challenge assay). Fifty women with a mammographic diagnosis negative for cancer (control group) and 100 women with a diagnosis of breast cancer (followed up during the treatment) were involved in this study. The significant DNA damage was observed by increasing in the index and frequency of damage along with the increasing of the frequency of micronuclei in peripheral blood and cells of the buccal mucosa, respectively. Despite the variability of the responses of breast cancer patients, the individuals presented lesions on the DNA, detected by the Comet assay and micronucleus Test, from the diagnosis until the end of the oncological treatment and were more susceptible to oxidative stress. We can conclude that the damages were due to clastogenic and/or aneugenic effects related to the neoplasia itself and that they increased, especially after RT.

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 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.

Butylated hydroxyanisole alleviates ferric nitrilotriacetate induced nephrotoxicity in rats by abrogation of oxidative stress

2013 ◽  
Vol 3 (2) ◽  
pp. 65-70
Author(s):  
Sabah Ansar ◽  
Mohammad Iqbal ◽  
Noura Al Jameil
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Lipid Peroxidation ◽  
Body Weight ◽  
Antioxidant Enzymes ◽  
Control Group ◽  
Butylated Hydroxyanisole ◽  
Chemopreventive Agent ◽  
Microsomal Lipid Peroxidation ◽  
Hydrogen Peroxide Generation

In this study the effect of butylated hydroxyanisole (BHA), a phenolic antioxidantused in food on Ferric‐Nitrilotriacetate (Fe–NTA) induced nephrotoxicity is reported. Fe‐NTA (9 mg Fe/kg body weight, intraperitoneally) treatment enhanced the renal microsomal lipid peroxidation and hydrogen peroxide generation to ~2‐2.5 folds compared to saline‐treated control and glutathione levels and the activities of antioxidant enzymes decreased to a range of 2–2.5 fold in kidney. These changes were reversed significantly in animals receiving a pretreatment of BHA. Pretreatment with BHA prior to Fe‐ NTA treatment reduced microsomal lipid peroxidation and hydrogen peroxide generation to 1.3‐1.5 fold compared to control group and glutathione and the activities of antioxidant enzymes increased to a range of 1.5‐2 folds in kidney. Fe‐NTA administration enhanced value of blood urea nitrogen and creatinine to 3.7 and 2.5 fold respectively as compared to their corresponding control group. Administration of Fe‐NTA to rats receiving a pretreatment of BHA led to a significant diminution in both of these values. The results indicate that BHA is a potent chemopreventive agent and suppresses Fe‐NTA induced nephrotoxicity in rats.

scholarly journals Effect of High-Dose Topical Minoxidil on Erythrocyte Quality in SKH1 Hairless Mice

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 731
Author(s):  
Eduardo Naranjo-Vázquez ◽  
María Guadalupe Sánchez-Parada ◽  
Belinda Claudia Gómez-Meda ◽  
Ana Lourdes Zamora-Perez ◽  
Martha Patricia Gallegos-Arreola ◽  
...  
Keyword(s):  
Dna Damage ◽  
Peripheral Blood ◽  
Micronucleus Assay ◽  
Control Group ◽  
High Dose ◽  
Entire Body ◽  
Hairless Mice ◽  
Mutagenic Potential ◽  
Polychromatic Erythrocytes ◽  
High Doses

SKH1 hairless mice are widely used in carcinogenesis and dermatology research due to their bare skin, as exposure to different agents is facilitated. Minoxidil is a cosmetic drug that is recognized as a mitogenic agent, and mitogens are suggested to have carcinogenic and mutagenic potential by inducing cell division and increasing the possibility of perpetuating DNA damage. Therefore, we hypothesized that the application of high doses of minoxidil to the skin of hairless mice would increase the number of micronucleated erythrocytes (MNEs) in peripheral blood. The objective of this study was to evaluate the topical administration of high doses of minoxidil on peripheral blood erythrocytes of SKH1 mice by means of micronucleus assay. Minoxidil was administered on the entire body surface of mice every 12 or 24 h. Minoxidil dosing every 24 h increased the number of micronucleated polychromatic erythrocytes (MNPCEs), and dosing every 12 h increased the number of MNEs and MNPCEs, as compared to baseline and the negative control group. No decrease in polychromatic erythrocyte frequencies was observed in the minoxidil groups. Therefore, topical application of high minoxidil doses to mice can produce DNA damage, as observed through an increase in the number of MNEs, without producing cytotoxicity, possibly due to its mitogenic effect.

scholarly journals INCREASED URINARY 8-OXO-7,8-DIHYDRO-2′-DEOXYGUANOSINE EXCRETION IN A SAMPLE OF EGYPTIAN CHILDREN WITH BETA THALASSEMIA MAJOR: MARKER FOR LIPID PEROXIDATION-INDUCED DNA DAMAGE

2017 ◽  
Vol 10 (12) ◽  
pp. 171
Author(s):  
Mona A Elabd ◽  
Dina Abu Zeid ◽  
Marwa A Elhady ◽  
Maged A El Wakeel ◽  
Ghada M El-kassas ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Dna Damage ◽  
Urinary Excretion ◽  
Serum Ferritin ◽  
Negative Correlation ◽  
Significant Negative Correlation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Increased Risk ◽  
Egyptian Children

Objective: The objective of this research was to evaluate oxidative stress status in children with β-thalassemia major.Methods: Our study was conducted in children with β-thalassemia aged from 5 to 15 years. Investigate the urinary excretion of human 8-oxo-7,8- dihydro-2′-deoxyguanosine, which will be analyzed by enzyme-linked immunosorbent assay. To investigate serum levels of antioxidant enzymes include glutathione s-transferase (GST) and catalase (CAT).Results: We found a significant elevation of the urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine level with p=0.001 compared to control group, a significant reduction of both GST and CAT p=0.05 and 0.03, respectively, compared to control group. There was a significant negative correlation between urinary 8-oxo-7,8-dihydro-2′-deoxyguanisine and CAT level, r=−0.378, p=0.016, hemoglobin - r=−0.610, p=0.001, hematocrit (%) - r=−0.478, p=0.002, while a significant positive correlation between urinary 8-oxo-7,8-dihydro-2′-deoxyguanisine and alanine aminotransferase - r=0.547, p=0.001, and serum ferritin - r=0.391, p=0.013. There was a significant negative correlation between CAT and serum ferritin - r=−0.320, p=0.44.Conclusion: We conclude that the strongly increased urinary excretion 8-oxo-7,8=dihydro-2′-deoxyguanisine indicates elevated lipid peroxidation induced DNA damage in internal organs such as the liver. These highly pro mutagenic lesions may contribute to the increased risk of thalassemia patients to develop hepatocellular carcinoma.

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