The role of molecular modelling strategies in validating the effects of chrysin on sodium arsenite-induced chromosomal and DNA damage

2018 ◽  
Vol 37 (10) ◽  
pp. 1037-1047 ◽  
Author(s):  
S Babangida ◽  
S Ibrahim ◽  
A Muhammad ◽  
DE Arthur ◽  
A Uzairu ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Bone Marrow ◽  
Dna Damage ◽  
Dna Fragmentation ◽  
Sodium Arsenite ◽  
Bone Marrow Cells ◽  
Hydrophobic Interactions ◽  
Protein Carbonyls ◽  
Strong Hydrogen Bond ◽  
Marrow Cells

Chrysin (CHR) is a food-based bioactive ingredient whereas, sodium arsenite (SA) is one of the major contaminant in drinking water. When ingested, SA contributes to tissue damage due to bioactivation by S-adenosyl methionine (SAM)-dependent methyltransferase. Hence, the needs to nullify this effect by investigating the potentials of CHR on SA-induced genotoxicity in rats. The experiment was divided into two successive stages (ameliorative and preventive, curative studies) for 1 week. Rats were divided into four groups: distilled water, 10mg/kg SA, 10mg/kg CHR and co-administration. In stage 2, the experimental groups were given either CHR or SA for 1 week, and treated in reversed order for additional week. Lipid peroxidation, protein carbonyl and DNA fragmentation in liver, blood brain and bone marrow cells micronucleus were assayed for using standard protocols. Molecular docking of SAM-dependent methyltransferase in the presence of CHR was conducted. CHR significantly ( p < 0.05) decreased the level of lipid peroxidation, protein carbonyls and DNA fragmentation in blood, liver and brain tissues as against group treated with SA. It also significantly ( p<0.05) reduced the level of micronuclei generated in bone marrow cells. The effects of CHR were shown to be ameliorative, preventive and curative in nature. Furthermore, CHR was able to dock (with binding energy of −24.81 kcal/mol and predicted inhibition kinetic constant (Ki) of 0.959 µM) into the active site of SAM-dependent methyltransferase with strong hydrogen bond and hydrophobic interactions. The study might have unravelled the potentials of CHR against SA-induced chromosomal and DNA damage, which might be due to inhibition of SAM-dependent methyltransferase.

scholarly journals Bone Marrow Oxidative Stress and Acquired Lineage-Specific Genotoxicity in Hematopoietic Stem/Progenitor Cells Exposed to 1,4-Benzoquinone

2020 ◽  
Vol 17 (16) ◽  
pp. 5865
Author(s):  
Ramya Dewi Mathialagan ◽  
Zariyantey Abd Hamid ◽  
Qing Min Ng ◽  
Nor Fadilah Rajab ◽  
Salwati Shuib ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Dna Damage ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Protein Carbonyls ◽  
Mouse Bone Marrow ◽  
Tail Moment ◽  
Erythroid Progenitor ◽  
Hematopoietic Stem

Hematopoietic stem/progenitor cells (HSPCs) are susceptible to benzene-induced genotoxicity. However, little is known about the mechanism of DNA damage response affecting lineage-committed progenitors for myeloid, erythroid, and lymphoid. Here, we investigated the genotoxicity of a benzene metabolite, 1,4-benzoquinone (1,4-BQ), in HSPCs using oxidative stress and lineage-directed approaches. Mouse bone marrow cells (BMCs) were exposed to 1,4-BQ (1.25–12 μM) for 24 h, followed by oxidative stress and genotoxicity assessments. Then, the genotoxicity of 1,4-BQ in lineage-committed progenitors was evaluated using colony forming cell assay following 7–14 days of culture. 1,4-BQ exposure causes significant decreases (p < 0.05) in glutathione level and superoxide dismutase activity, along with significant increases (p < 0.05) in levels of malondialdehyde and protein carbonyls. 1,4-BQ exposure induces DNA damage in BMCs by significantly (p < 0.05) increased percentages of DNA in tail at 7 and 12 μM and tail moment at 12 μM. We found crucial differences in genotoxic susceptibility based on percentages of DNA in tail between lineage-committed progenitors. Myeloid and pre-B lymphoid progenitors appeared to acquire significant DNA damage as compared with the control starting from a low concentration of 1,4-BQ exposure (2.5 µM). In contrast, the erythroid progenitor showed significant damage as compared with the control starting at 5 µM 1,4-BQ. Meanwhile, a significant (p < 0.05) increase in tail moment was only notable at 7 µM and 12 µM 1,4-BQ exposure for all progenitors. Benzene could mediate hematological disorders by promoting bone marrow oxidative stress and lineage-specific genotoxicity targeting HSPCs.

scholarly journals Friend Leukemia Virus Infection Enhances DNA Damage-Induced Apoptosis of Hematopoietic Cells, Causing Lethal Anemia in C3H Hosts

2002 ◽  
Vol 76 (15) ◽  
pp. 7790-7798 ◽  
Author(s):  
Masanobu Kitagawa ◽  
Shuichi Yamaguchi ◽  
Maki Hasegawa ◽  
Kaoru Tanaka ◽  
Toshihiko Sado ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Knockout Mice ◽  
Bone Marrow Cells ◽  
Leukemia Virus ◽  
Hematopoietic Cells ◽  
Friend Leukemia ◽  
C3h Mice ◽  
Friend Leukemia Virus ◽  
Marrow Cells

ABSTRACT Exposure of hematopoietic progenitors to gamma irradiation induces p53-dependent apoptosis. However, host responses to DNA damage are not uniform and can be modified by various factors. Here, we report that a split low-dose total-body irradiation (TBI) (1.5 Gy twice) to the host causes prominent apoptosis in bone marrow cells of Friend leukemia virus (FLV)-infected C3H mice but not in those of FLV-infected DBA mice. In C3H mice, the apoptosis occurs rapidly and progressively in erythroid cells, leading to lethal host anemia, although treatment with FLV alone or TBI alone induced minimal apoptosis in bone marrow cells. A marked accumulation of P53 protein was demonstrated in bone marrow cells from FLV-infected C3H mice 12 h after treatment with TBI. Although a similar accumulation of P53 was also observed in bone marrow cells from FLV-infected DBA mice treated with TBI, the amount appeared to be parallel to that of mice treated with TBI alone and was much lower than that of FLV- plus TBI-treated C3H mice. To determine the association of p53 with the prominent enhancement of apoptosis in FLV- plus TBI-treated C3H mice, p53 knockout mice of the C3H background (C3H p53−/− ) were infected with FLV and treated with TBI. As expected, p53 knockout mice exhibited a very low frequency of apoptosis in the bone marrow after treatment with FLV plus TBI. Further, C3H p53−/− → C3H p53+/+ bone marrow chimeric mice treated with FLV plus TBI survived even longer than the chimeras treated with FLV alone. These findings indicate that infection with FLV strongly enhances radiation-induced apoptotic cell death of hematopoietic cells in host animals and that the apoptosis occurs through a p53-associated signaling pathway, although the response was not uniform in different host strains.

An oxovanadium(IV) complex protects murine bone marrow cells against cisplatin-induced myelotoxicity and DNA damage

2016 ◽  
Vol 40 (3) ◽  
pp. 359-367 ◽  
Author(s):  
Abhishek Basu ◽  
Arin Bhattacharjee ◽  
Amalesh Samanta ◽  
Sudin Bhattacharya
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Bone Marrow Cells ◽  
Murine Bone Marrow ◽  
Marrow Cells

Prolonged Quercetin Administration Diminishes the Etoposide-Induced DNA Damage in Bone Marrow Cells of Rats

2007 ◽  
Vol 30 (1) ◽  
pp. 67-81 ◽  
Author(s):  
Maria Kapiszewska ◽  
Agnieszka Cierniak ◽  
Monika A. Papiez ◽  
Agata Pietrzycka ◽  
Marek Stepniewski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Bone Marrow Cells ◽  
Marrow Cells

Pendimethalin induces oxidative stress, DNA damage, and mitochondrial dysfunction to trigger apoptosis in human lymphocytes and rat bone-marrow cells

2017 ◽  
Vol 149 (2) ◽  
pp. 127-141 ◽  
Author(s):  
Sabiha M. Ansari ◽  
Quaiser Saquib ◽  
Sabry M. Attia ◽  
Eslam M. Abdel-Salam ◽  
Hend A. Alwathnani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Dna Damage ◽  
Mitochondrial Dysfunction ◽  
Bone Marrow Cells ◽  
Human Lymphocytes ◽  
Rat Bone ◽  
Marrow Cells

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.

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