scholarly journals Therapeutic effects of statins on chromosomal DNA damage of dyslipidemic patients

2019 ◽  
Vol 244 (13) ◽  
pp. 1089-1095 ◽  
Author(s):  
Hamiyet Donmez-Altuntas ◽  
Fahri Bayram ◽  
Ayse N Coskun-Demirkalp ◽  
Osman Baspınar ◽  
Derya Kocer ◽  
...  
Keyword(s):  
Dna Damage ◽  
Statin Therapy ◽  
Oxidative Dna Damage ◽  
Nuclear Division ◽  
Statin Treatment ◽  
Therapeutic Effects ◽  
Chromosomal Dna ◽  
Control Subjects ◽  
Before And After ◽  
Nuclear Division Index

Statins are a group of cholesterol lowering drugs and frequently used in the therapy of dyslipidemia. Our knowledge of the impact of statin therapy on DNA damage is as yet rudimentary. In this study, we aimed to assess the possible (1) genotoxic, cytostatic, and cytotoxic effects of statins in peripheral blood lymphocytes by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay, and (2) oxidative DNA damage by measuring plasma 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in response to statin therapy. Thirty patients with dyslipidemia who had no chronic diseases and did not use any medicines that interfere lipid values and twenty control subjects were included in the study. Statin therapy was initiated at risk-stratified doses. Blood samples were taken before and after treatment with statins and from control subjects, and CBMN-cyt assay parameters and 8-OHdG levels were evaluated. The chromosomal DNA damage (micronuclei and nucleoplasmic bridges [NPBs]), cytostasis (nuclear division index [NDI]), and cytotoxicity (apoptotic and necrotic cell frequencies) were decreased in patients with dyslipidemia after statin treatment. No significant differences were found for 8-OHdG levels between patients with dyslipidemia before or after statin therapy. The total cholesterol and low-density lipoprotein-cholesterol levels showed positive correlations with NPB frequency in patients with dyslipidemia prior to statin treatment. The present study is the first to evaluate CBMN-cyt assay biomarkers and 8-OHdG levels in patients with dyslipidemia before and after treatment with statins. The observed reductions of chromosomal DNA damage and NDI values with statin treatment could represent an important and under-appreciated pleiotropic effect of these agents. Impact statement In literature, it is possible to find some in vitro cytokinesis-block micronucleus (CBMN) assay studies about human lymphocytes and statins. But, there are no data on CBMN-cytome (CBMN-cyt) assay parameters related to statin therapy in patients with dyslipidemia. The present study is the first to evaluate CBMN-cyt assay biomarkers and 8-OHdG levels in patients with dyslipidemia before treatment and after treatment with statins (5–10 mg/day rosuvastatin or 10–20 mg/day atorvastatin). In this study we show that statin therapy decreased chromosomal DNA damage (micronuclei and nucleoplasmic bridges) and nuclear division index (NDI) values in patients with dyslipidemia by possible molecular reasons independent of oxidative DNA damage. In addition, the decrease of chromosomal DNA damage and NDI values with statin treatment could be indicated by the association between statin use and reduced risk of cancer.

scholarly journals Genotoxicity of Marijuana in Mono-Users

2021 ◽  
Vol 12 ◽  
Author(s):  
Eunice Fabian-Morales ◽  
Carmen Fernández-Cáceres ◽  
Adriana Gudiño ◽  
Marco A. Andonegui Elguera ◽  
Karla Torres-Arciga ◽  
...  
Keyword(s):  
Dna Damage ◽  
Illicit Drugs ◽  
Nuclear Division ◽  
Peripheral Blood Lymphocytes ◽  
Control Group ◽  
Chromosomal Damage ◽  
Chromosomal Dna ◽  
Genotoxic Effects ◽  
Nuclear Division Index ◽  
Definition Of

Marijuana (Cannabis sp.) is among the most recurred controlled substances in the world, and there is a growing tendency to legalize its possession and use; however, the genotoxic effects of marijuana remain under debate. A clear definition of marijuana's genotoxic effects remains obscure by the simultaneous consumption of tobacco and other recreational substances. In order to assess the genotoxic effects of marijuana and to prevent the bias caused by the use of substances other than cannabis, we recruited marijuana users that were sub-divided into three categories: (1) users of marijuana-only (M), (2) users of marijuana and tobacco (M+T), and (3) users of marijuana plus other recreative substances or illicit drugs (M+O), all the groups were compared against a non-user control group. We quantified DNA damage by detection of γH2AX levels and quantification of micronuclei (MN), one of the best-established methods for measuring chromosomal DNA damage. We found increased levels of γH2AX in peripheral blood lymphocytes from the M and M+T groups, and increased levels of MNs in cultures from M+T group. Our results suggest a DNA damage increment for M and M+T groups but the extent of chromosomal damage (revealed here by the presence of MNs and NBuds) might be related to the compounds found in tobacco. We also observed an elevated nuclear division index in all marijuana users in comparison to the control group suggesting a cytostatic dysregulation caused by cannabis use. Our study is the first in Mexico to assess the genotoxicity of marijuana in mono-users and in combination with other illicit drugs.

scholarly journals Role of Bacillus subtilis Error Prevention Oxidized Guanine System in Counteracting Hexavalent Chromium-Promoted Oxidative DNA Damage

2014 ◽  
Vol 80 (17) ◽  
pp. 5493-5502 ◽  
Author(s):  
Fernando Santos-Escobar ◽  
J. Félix Gutiérrez-Corona ◽  
Mario Pedraza-Reyes
Keyword(s):  
Dna Damage ◽  
Bacillus Subtilis ◽  
Hexavalent Chromium ◽  
Oxidative Dna Damage ◽  
Chromosomal Dna ◽  
Error Prevention ◽  
Content Type ◽  
Induced Mutagenesis ◽  
Oxidized Guanine ◽  
Life On Earth

ABSTRACTChromium pollution is potentially detrimental to bacterial soil communities, compromising carbon and nitrogen cycles that are essential for life on earth. It has been proposed that intracellular reduction of hexavalent chromium [Cr(VI)] to trivalent chromium [Cr(III)] may cause bacterial death by a mechanism that involves reactive oxygen species (ROS)-induced DNA damage; the molecular basis of the phenomenon was investigated in this work. Here, we report thatBacillus subtiliscells lacking a functional error prevention oxidized guanine (GO) system were significantly more sensitive to Cr(VI) treatment than cells of the wild-type (WT) strain, suggesting that oxidative damage to DNA is involved in the deleterious effects of the oxyanion. In agreement with this suggestion, Cr(VI) dramatically increased the ROS concentration and induced mutagenesis in a GO-deficientB. subtilisstrain. Alkaline gel electrophoresis (AGE) analysis of chromosomal DNA of WT and ΔGO mutant strains subjected to Cr(VI) treatment revealed that the DNA of the ΔGO strain was more susceptible to DNA glycosylase Fpg attack, suggesting that chromium genotoxicity is associated with 7,8-dihydro-8-oxodeoxyguanosine (8-oxo-G) lesions. In support of this notion, specific monoclonal antibodies detected the accumulation of 8-oxo-G lesions in the chromosomes ofB. subtiliscells subjected to Cr(VI) treatment. We conclude that Cr(VI) promotes mutagenesis and cell death inB. subtilisby a mechanism that involves radical oxygen attack of DNA, generating 8-oxo-G, and that such effects are counteracted by the prevention and repair GO system.

Analysis of oxidative DNA damage and HPRT mutant frequencies in cancer patients before and after radiotherapy

1999 ◽  
Vol 431 (2) ◽  
pp. 361-369 ◽  
Author(s):  
Ivo H Zwingmann ◽  
Irene J Welle ◽  
John J.M Engelen ◽  
Pauline A.E.L Schilderman ◽  
Jos M.A de Jong ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Patients ◽  
Oxidative Dna Damage ◽  
Before And After

scholarly journals Acute Toxicity and DNA Instability Induced by Exposure to Low Doses of Triclosan and Phthalate DEHP, and Their Combinations, in vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Nathalia de Assis Aguilar Duarte ◽  
Lindiane Eloisa de Lima ◽  
Flora Troina Maraslis ◽  
Michael Kundi ◽  
Emilene Arusievicz Nunes ◽  
...  
Keyword(s):  
Dna Damage ◽  
Acute Toxicity ◽  
Nuclear Division ◽  
Aquatic Organisms ◽  
Human Cells ◽  
Dna Instability ◽  
Nuclear Division Index ◽  
Mutagenic Effects ◽  
The Impact

Triclosan (TCS) is an antimicrobial agent widely used in personal care products (PCP) and the di-(2-ethyl hydroxy-phthalate) (DEHP) is a chemical compound derived from phthalic acid, used in medical devices and plastic products with polyvinyl chloride (PVCs). As result of their extensive use, TCS and DEHP have been found in the environment and previous studies demonstrated the association between their exposure and toxic effects, mostly in aquatic organisms, but there is a shortage in the literature concerning the exposure of TCS and DEHP in human cells. The aim of the present study was to assess the impact of exposure to TCS and DEHP, as well as their combinations, on biomarkers related to acute toxicity and DNA instability, in HepG2 cells, by use of cytokinesis-block micronucleus cytome (CBMNCyt) assay. For that, the cultures were exposed to TCS, DEHP and combinations at doses of 0.10, 1.0, and 10 μM for the period of 4 h and the parameters related to DNA damage (i.e., frequencies of micronuclei (MN) and nuclear buds (NBUDs), to cell division (i.e., nuclear division index (NDI) and nuclear division cytotoxic index (NDCI) and to cell death (apoptotic and necrotic cells) were scored. Clear mutagenic effects were seen in cells treated with TCS, DEHP at doses of 1.0 and 10 μM, but no combined effects were observed when the cells were exposed to the combinations of TCS + DEHP. On the other hand, the combination of the toxicants significantly increased the frequencies of apoptotic and necrotic cells, as well as induced alterations of biomarkers related to cell viability (NDI and NDCI), when compared to the groups treated only with TCS or DEHP. Taken together, the results showed that TCS and DEHP are also able to induce acute toxicity and DNA damage in human cells.

scholarly journals Effect of Imidocarb Application on Oxidative DNA Damage Caused by Anaplasmosis

2021 ◽  
Vol 9 (12) ◽  
pp. 2308-2311
Author(s):  
Ahmet Cihat Öner ◽  
Adnan Ayan
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Dna Fragmentation ◽  
Oxidative Dna Damage ◽  
Clinical Signs ◽  
Tail Length ◽  
Assay Method ◽  
Control Group ◽  
Tail Moment ◽  
Before And After

This study was aimed to evaluate DNA fragmentation by using Comet assay in naturally infected sheep with Anaplasmosis before and after treatment with the Comet method, which shows DNA damage specifically. In the study, blood samples were collected from 10 Anaplosmosis infected and 10 healthy sheep. The anaplosmosis was diagnosed by clinical signs and symptoms. The infection was confirmed by Giemsa staining. The blood was collected from control group and infected group before and after the treatment, from the vena jugularis with the appropriate method. The DNA fragmentation was checked by using the Comet assay of blood cells. The data were analysed throught ANNOVA one-way. The result showed higher DNA fragmentation in sick animals diagnosed with anaplasmosis; tail length and tail moment values were found to be statistically significantly higher than the control group. When the data obtained after imidocarb (IMD) application were compared with obtained during the disease, a decreased DNA damage and tail moment was determined, however, these values higher than control. In this study, DNA damage and the extent of this damage were investigated by the Comet assay method using a healthy control group before and after treatment in animals with Anaplasmosis. When the findings obtained from the study were evaluated, it was seen that Anaplasma agents caused DNA damage and with the imidocarb application given for treatment, DNA damage was reduced and results close to healthy individuals were obtained.

scholarly journals Increased Chromosomal and Oxidative DNA Damage in Patients with Multinodular Goiter and Their Association with Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Hamiyet Donmez-Altuntas ◽  
Fahri Bayram ◽  
Nazmiye Bitgen ◽  
Sibel Ata ◽  
Zuhal Hamurcu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Thyroid Cancer ◽  
Multinodular Goiter ◽  
Oxidative Dna Damage ◽  
Thyroid Nodules ◽  
Clinical Problem ◽  
Peripheral Blood Lymphocytes ◽  
Chromosomal Dna ◽  
Increased Risk ◽  
Cancer Types

Thyroid nodules are a common clinical problem worldwide. Although thyroid cancer accounts for a small percentage of thyroid nodules, the majority are benign. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) levels are a marker of oxidative stress and play a key role in the initiation and development of a range of diseases and cancer types. This study evaluates cytokinesis-block micronucleus cytome (CBMN-cyt) assay parameters and plasma 8-OHdG levels and their association with thyroid nodule size and thyroid hormones in patients with multinodular goiter. The study included 32 patients with multinodular goiter and 18 age- and sex-matched healthy controls. CBMN-cyt assay parameters in peripheral blood lymphocytes of patients with multinodular goiter and controls were evaluated, and plasma 8-OHdG levels were measured. The micronucleus (MN) frequency (chromosomal DNA damage), apoptotic and necrotic cells (cytotoxicity), and plasma 8-OHdG levels (oxidative DNA damage) were significantly higher among patients with multinodular goiter. Our study is the first report of increased chromosomal and oxidative DNA damage in patients with multinodular goiter, which may predict an increased risk of thyroid cancer in these patients. MN frequency and plasma 8-OHdG levels may be markers of the carcinogenic potential of multinodular goiters and could be used for early detection of different cancer types, including thyroid cancer.

Determination of pre and post treatment oxidative status and oxidative DNA damage in diarrheic calves

2015 ◽  
Vol 49 (6) ◽  
Author(s):  
Mustafa Kabu ◽  
Ibrahim Hakki Cigerci ◽  
Cangir Uyarlar ◽  
Haci Ahmet Celik
Keyword(s):  
Dna Damage ◽  
Body Temperature ◽  
Dry Matter ◽  
Oxidative Dna Damage ◽  
High Energy ◽  
Oxidative Status ◽  
Blood Samples ◽  
Damage Level ◽  
Before And After ◽  
Diarrheic Calves

Increase in production of free radicals causes damage in lipids of cell membrane, weakening in functions of cell proteins and DNA damage. The aim of the present study was to determine the oxidative status, level of oxidative DNA damage and treatment effectiveness on these parameters on diarrheic calves. The study was conducted using 10 clinically holstein calves from 2-3 months of age. Antidiarrheic treatment containing Amonium sulphate (30mg/kg/day, Gabbrocol, Ceva Inc.), a mixture of Bismuth subcarbonate, kaolin, pectin (10g/day, Bismol, Bioteknik Inc.), vitamin and mineral mixture (105g/day, Sky High Energy, Egevet Co.Ltd) as drugs orally administered to all calves for 3 days. Body temperature, feces and blood samples were taken before and after treatment. Dry matter measured (%) in feces, DNA damage level and some hematologic parameters, total oxidant status (TOS), total antioxidant status (TAS) and some biochemical parameters were measured from blood samples. HB, ALT, TP levels did not differ before and after treatment. However, body temperature (p<0.01), WBC (p<0.01), HCT (p<0.05), GGT (p<0.01), TOS (p<0.05), DNA damage (p<0.05) were decreased, dry matter in feces (p<0.01), RBC (p<0.05), AST (p<0.01), Albumin (p<0.01) and TAS (p<0.05) were increased after treatment. The results of the study indicate that oxidative DNA damage increases with degenerative diseases such as diarrhea and decreases to the normal range after effective treatment. It can be suggested from these results that oxidative DNA damage might be a good indicator to reveal the degeneration level of diarrhea in animals and a good parameter to evaluate the effectiveness of the treatment in terms of cellular form.

scholarly journals Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Elisabeth C. van der Slikke ◽  
Bastiaan S. Star ◽  
Matijs van Meurs ◽  
Robert H. Henning ◽  
Jill Moser ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Mrna Expression ◽  
Oxidative Dna Damage ◽  
Umbilical Vein ◽  
University Teaching ◽  
Mitochondrial Mass ◽  
Control Subjects ◽  
Mitochondrial Dna Damage ◽  
And Control

Abstract Background Sepsis is a life-threatening condition accompanied by organ dysfunction subsequent to a dysregulated host response to infection. Up to 60% of patients with sepsis develop acute kidney injury (AKI), which is associated with a poor clinical outcome. The pathophysiology of sepsis-associated AKI (sepsis-AKI) remains incompletely understood, but mitochondria have emerged as key players in the pathogenesis. Therefore, our aim was to identify mitochondrial damage in patients with sepsis-AKI. Methods We conducted a clinical laboratory study using “warm” postmortem biopsies from sepsis-associated AKI patients from a university teaching hospital. Biopsies were taken from adult patients (n = 14) who died of sepsis with AKI at the intensive care unit (ICU) and control patients (n = 12) undergoing tumor nephrectomy. To define the mechanisms of the mitochondrial contribution to the pathogenesis of sepsis-AKI, we explored mRNA and DNA expression of mitochondrial quality mechanism pathways, DNA oxidation and mitochondrial DNA (mtDNA) integrity in renal biopsies from sepsis-AKI patients and control subjects. Next, we induced human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS) for 48 h to mimic sepsis and validate our results in vitro. Results Compared to control subjects, sepsis-AKI patients had upregulated mRNA expression of oxidative damage markers, excess mitochondrial DNA damage and lower mitochondrial mass. Sepsis-AKI patients had lower mRNA expression of mitochondrial quality markers TFAM, PINK1 and PARKIN, but not of MFN2 and DRP1. Oxidative DNA damage was present in the cytosol of tubular epithelial cells in the kidney of sepsis-AKI patients, whereas it was almost absent in biopsies from control subjects. Oxidative DNA damage co-localized with both the nuclei and mitochondria. Accordingly, HUVECs induced with LPS for 48 h showed an increased mnSOD expression, a decreased TFAM expression and higher mtDNA damage levels. Conclusion Sepsis-AKI induces mitochondrial DNA damage in the human kidney, without upregulation of mitochondrial quality control mechanisms, which likely resulted in a reduction in mitochondrial mass.

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