Damage In Peripheral Blood Cells Research Articles

Reactive oxygen species-responsive nanodrug of natural crocin-i with prolonged circulation for effective radioprotection

With the progress of nuclear technology including radiotherapy and radiodiagnosis, radiation has been widely used in many fields as a powerful diagnostic and therapeutic tool in the medical area. Unfortunately, acute radiation disease will occur if the human body is accidentally exposed to a large dosage of ionizing radiation. However, clinical radioprotective agents are being challenged by the short half-life and several side effects. In this work, a reactive oxygen species-responsive nanodrug is developed for efficient radioprotection. The nanodrug was prepared by modifying Crocin-I with 4-pentylphenylboronic acid (PBA) and exhibited effective responsiveness and scavenging activity of reactive oxygen species. PBA-Crocin nanodrug displayed good biocompatibility and radioprotection effect compared to Crocin-I in vitro. The survival rate of cells treated with PBA-Crocin (10 μg mL−1) is comparable to that treated with amifostine (12.5 μg mL−1, the only radioprotector approved by the United States Food and Drug Administration clinically) after 6 Gy irradiation. Importantly, PBA-Crocin resulted in markedly prevention of radiation-induced damage in peripheral blood cells and a 1.6-fold longer retention time of Crocin-I in plasma in comparison with Crocin-I. The finding suggests a new design for natural medicine in effective radioprotection.

In vitro assessment of genotoxic and cytotoxic effects of Artemisia annua L. tincture


 
 The genus Artemisia (fam. Asteraceae) is one of the largest and widely distributed with around 500 species, majority used as aromatic and medicinal plants. Artemisia annua L. is widely used as a dietary spice, herbal tea, as a supplement, and in a non-pharmaceutical form for treatment of malaria and fever. It is orally consumed as capsules, extracts and tinctures and topically applied as an essential oil diluted in lotions and ointments. Artemisinin is the main constituent of Artemisia annua L. extracts. Since the discovery that the artemisinin is efficient in malaria treatment, there is also a growth in consumption of A. annua extracts for antitumour and even recently for antiviral treatments against SARS-CoV-2 infections. This study aimed to investigate genotoxic effect in peripheral blood culture and cytotoxic effects in cancer and normal cell lines, of commercially available A. annua L. tincture in series of dilutions. Both comet and neutral red uptake assays revealed dose-dependent genotoxicity and cytotoxicity of A. annua tincture dilutions. Comet assay revealed significantly increased DNA damage in peripheral blood cells while neutral-red assays showed increase in cytotoxicity (p<0.001) in both normal and cancer cell cultures treated with the lowest extract dilution compared to the highest one applied. Obtained results indicate caution needed in A. annua L. tincture use, especially when poorly diluted.
 
 
 
 

Traditional weight loss and dukan diets as to nutritional and laboratory results

Traditional weight loss and dukan diets as to nutritional and laboratory results

Brazil nut prevents oxidative DNA damage in type 2 diabetes patients

The Brazil nut (Bertholletia excelsa, H.B.K.) originating from the Amazon region is one of the richest known sources of selenium (Se), a micronutrient that is essential and required for optimal physiological functioning. This mineral presents several health benefits, including improvement of the redox cellular status and maintenance of genomic stability. Knowing that type 2 diabetes mellitus (T2D) is strongly linked to oxidative stress and consequently DNA damage, the aim of this study was to assess the ex vivo antioxidative effects of Se through Brazil nut consumption and its potential in preventing oxidative DNA damage induced by H2O2. In order to accomplish this, the Comet assay (single-cell gel electrophoresis) was used to measure DNA damage in peripheral blood cells harvested before and after supplementation with Brazil nut. Comet assay was also applied ex vivo to measure the potential of Se to prevent oxidative damage to DNA induced by H2O2 in blood of type 2 diabetes patients collected before and after six months of supplementation with Brazil nut. We found that supplementation with Brazil nuts significantly increased serum Se levels. Furthermore, we observed a significant increase in fasting blood glucose after six months of consuming Brazil nuts; however, no significant effect was observed on the levels of glycated hemoglobin. Finally, we noticed that the cells were more resistant to H2O2-induced DNA damage after six months of supplementation with Brazil nut. Thus, consumption of Brazil nuts could decrease oxidative DNA damage in T2D patients, probably through the antioxidative effects of Se.

Genomic Instability in Peripheral Blood and Buccal Mucosal Cells of Marijuana Smokers: The Impact of Tobacco Smoke.

Background:The aim of this study was to evaluate cytotoxic, mutagenic and genotoxic effects on buccal mucosa and peripheral blood cells from marijuana and tobacco smokers. Methods:For this purpose, a total of 45 volunteers were distributed into four groups: CTRL group (control): individuals who did not smoke marijuana or tobacco (n = 11); Group M: Marijuana smokers (n = 13); Group T: Tobacco smokers (n = 13); Group M + T: Smokers of both marijuana and tobacco (n = 08). Results:Smokers of both marijuana and tobacco led an increase of micronucleated cells on buccal mucosa when compared to control group. The occurrence of karyolysis showed significant changes in this group as well. The comet assay data revealed genetic damage in peripheral blood cells for all groups of smokers. Conclusion:In summary, our results showed that marijuana and /or tobacco are able to induce genetic damage and cytotoxicity in oral and peripheral blood cells.

Genotoxicity assessment of fipronil (frontline plus®) in Canis familiaris

ABSTRACT: Fipronil is a pesticide widely used for controlling fleas and ticks in domestic animals, and its short-term exposure can lead to serious effects on animals. However, the possible genotoxic effect of this compound has not been investigated in target animals. Based on the hypothesis that fipronil can induce genotoxicity, this study evaluated the effect of fipronil on DNA damage in peripheral blood cells. For that purpose, ten dogs of both sexes were used in the study. The product (6.7mg/kg) was applied on the dorsal neck region of each animal. Peripheral blood samples were collected immediately prior to application of the product, and at 3, 8 and 24 hours after the application. Samples were processed for comet assay. No statistically significant differences were found among the four time points. The current study suggests for the first time that a single exposure to this pesticide does not induce systemic genotoxic effect in dogs.

Antigenotoxic Effect of Piperine in Broiler Chickens Intoxicated with Aflatoxin B1.

Piperine is an abundant amide extracted from black pepper seeds which has been shown to have protective effects against cytotoxic and genotoxic carcinogenesis induced by certain chemical carcinogens and aflatoxin B1 (AFB1) in vitro. The aim of this work was to study, in vivo, the antigenotoxic potential of feed-added piperine on broiler chickens experimentally intoxicated with AFB1, using micronucleus and comet assays. The antigenotoxicity assessment of 9-day-old chicks was performed on a total of 60 chickens divided into four groups of 15 broilers each: (C) control, (P) 60 mg·piperine kg−1 feed, (A) 0.5 mg·AFB1·kg−1 body weight, (daily by oral route), and (P + A) co-treatment with piperine and AFB1. The experiment was conducted for 26 days. Chicks intoxicated with AFB1 showed significant genotoxic effects in the first 24 h post intoxication, and the effects remained in the other periods analyzed (48, 72, and 96 h and 26 days of treatment). The DNA damage in peripheral blood cells, the number of erythrocytes with micronuclei, and polychromatic-to-normochromatic erythrocyte ratio were significantly reduced or absent in the piperine/AFB1 group. No significant differences were observed between the group piperine/AFB1 and the control and piperine-alone groups. The addition 60 mg·kg−1 of piperine to the diet of the broiler chicks was safe, promoting beneficial effects in poultry health with respect to the toxic effects 0.5 mg·AFB1·kg−1 body weight.

DNA damage in blood cells exposed to low-level lasers.

In regenerative medicine, there are increasing applications of low-level lasers in therapeutic protocols for treatment of diseases in soft and in bone tissues. However, there are doubts about effects on DNA, and an adequate dosimetry could improve the safety of clinical applications of these lasers. This work aimed to evaluate DNA damage in peripheral blood cells of Wistar rats induced by low-level red and infrared lasers at different fluences, powers, and emission modes according to therapeutic protocols. Peripheral blood samples were exposed to lasers and DNA damage was accessed by comet assay. In other experiments, DNA damage was accessed in blood cells by modified comet assay using formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III enzymes. Data show that exposure to low-level red and infrared lasers induce DNA damage depending on fluence, power and emission mode, which are targeted by Fpg and endonuclease III. Oxidative DNA damage should be considered for therapeutic efficacy and patient safety in clinical applications based on low-level red and infrared lasers.

Iron Oxide Nanoparticles Induced Oxidative Damage in Peripheral Blood Cells of Rat

Nanotechnology is a rapidly growing field that has elicited much concern due to a variety of applications in different fields such as industry, medicine, and cosmetics. These developments increase the concern among the general population. Hence, there is an urgent need to explore the possible human health effects of these nanomaterials. The present study is aimed to evaluate the cytotoxic and genotoxic effects of iron oxide nanoparticles (IONPs) in-vivo. In order to study the toxic effects, Wistar rats were administered intravenously with various doses of IONPs (Fe2O3) through caudal vein once in a week for 28 days, and various biochemical assays such as antioxidant enzymes activity (SOD, CAT, and GSH), lipid peroxidation, DNA damage and hematological parameters were evaluated. Genotoxicity was evaluated by comet assay and oxidative stress was measured by anti-oxidant enzymes. The results reveal that IONPs alter hematological factor such as RBC counts, WBC counts, neutrophils, monocytes and hemoglobin. A dose-dependent inhibition (p < 0.05) of antioxidant enzymes was found, and meanwhile the level of MDA elevated significantly (p < 0.05) in IONPs treated groups in dose-dependent manner; however comet assay results indicate that IONPs did not induce any significant DNA damage. The present study concluded that IONP affects inflammatory response, which induces the oxidative stress and may adversely affect the cellular function.

Mimosa (Mimosa caesalpiniifolia) prevents oxidative DNA damage induced by cadmium exposure in Wistar rats

The Mimosa (Mimosa caesalpiniifolia) is a plant native from South America; it is used in the traditional medicine systems for treating bacterial, fungal, parasitic and inflammatory conditions. The aim of this study was to evaluate the antigenotoxic and antioxidant activities induced by mimosa (M. caesalpiniifolia) in multiple rodent organs subjected to intoxication with cadmium chloride. A total of 40 Wistar rats (8 weeks old, 250 g) were distributed into eight groups (n = 5), as follows: Control group (non-treated group, CTRL); Cadmium exposed group (Cd); cadmium exposure and treated with extract at 62.5 mg/kg/day; cadmium exposure and treated with extract at 125 mg/kg/day; cadmium exposure and treated with extract at 250 mg/kg/day; cadmium exposure and treated with ethyl acetate fraction at 62.5 mg/kg/day. For evaluating the toxicogenetic potential of mimosa, two groups were included in the study being treated with extract at 250 mg/kg/day and acetate fraction of mimosa at 62 mg/kg/day, only. Extract of mimosa at concentrations of 62.5 and 125 mg decreased DNA damage in animals intoxicated with cadmium when compared to cadmium group. In a similar manner, treatment with ethyl acetate fraction of mimosa at 62.5 mg concentration in animals previously exposed to cadmium reduced genetic damage in peripheral blood cells. In a similar manner, the treatment with ethyl acetate fraction reduced DNA damage in liver cells. Oxidative DNA damage was reduced to animals exposed to cadmium and treated with 125 mg of extract as well as those intoxicated to cadmium and treated with 62.5 of acetate fraction of mimosa. Taken together, our results indicate that mimosa prevents genotoxicity induced by cadmium exposure in liver and peripheral blood cells of rats as a result of antioxidant activity.

Patients with Systemic Sclerosis Present Increased DNA Damage Differentially Associated with DNA Repair Gene Polymorphisms

Patients with systemic sclerosis (SSc) exhibit increased toxicity when exposed to genotoxic agents. In our study, we evaluated DNA damage and polymorphic sites in 2 DNA repair genes (XRCC1 Arg399Gln and XRCC4 Ile401Thr) in patients with SSc. A total of 177 patients were studied for DNA repair gene polymorphisms. Fifty-six of them were also evaluated for DNA damage in peripheral blood cells using the comet assay. Compared to controls, the patients as a whole or stratified into major clinical variants (limited or diffuse skin involvement), irrespective of the underlying treatment schedule, exhibited increased DNA damage. XRCC1 (rs: 25487) and XRCC4 (rs: 28360135) allele and genotype frequencies observed in patients with SSc were not significantly different from those observed in controls; however, the XRCC1 Arg399Gln allele was associated with increased DNA damage only in healthy controls and the XRCC4 Ile401Thr allele was associated with increased DNA damage in both patients and controls. Further, the XRCC1 Arg399Gln allele was associated with the presence of antinuclear antibody and anticentromere antibody. No association was observed between these DNA repair gene polymorphic sites and clinical features of patients with SSc. These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of the XRCC1 and XRCC4 DNA repair genes may differentially influence DNA damage and the development of autoantibodies.

Limb compression induces multi-system genetic damage in rats

Muscle crush injury is a common trauma in the modern society after as a result of mass disasters after penetration into muscle by high-velocity projectiles, blunt external trauma, or by gravity during prolonged immobilization in comatose patients after head trauma, alcoholic or drug overdose. However, the underlying mechanisms linking these alterations are still not fully understood, especially in acute phase. The aim of this study was to analyze genomic instability in multiple organs of rats after acute muscle injury by means of single cell gel (comet) assay. Rats were randomly distributed into three groups (n=6 each group): control group and experimental groups: sacrificed 6h as 12h after muscle compression. These results indicate genetic damage in peripheral blood cells as depicted by tail moment results. DNA breakage was also detected in liver, lung and kidney cells after acute muscle injury for two times evaluated. Heart cells showed genetic damage after 12h following muscle compression. Taken together, our results suggest that acute muscle injury induces genomic damage in multiple organs of Wistar rats. This novel finding offers new insights into the underlying mechanisms of the relationship between acute crush muscle injury and clinical manifestations that can occur during limb compression.

Insulin resistance is associated with DNA damage in peripheral blood cells in non-diabetic patients with genotype 1 chronic hepatitis C

Background. In chronic liver diseases of different etiologies, including viral hepatitis, genotoxic effects of oxidative stress have been shown, both in clinical and in experimental conditions, suggesting that this mechanism may contribute to the evolution of the disease. Aim. To evaluate DNA damage in the peripheral blood of untreated non-diabetic patients with chronic hepatitis C and control subjects, and its correlation with demographic, anthropometric, biochemical, and histological parameters in the patient sample. Patients and methods. This study comprised 100 subjects of both genders, 60 of whom were treatment-naïve patients with positive serology for genotype 1 hepatitis C. The remaining 40 were blood donors with negative serology for hepatitis who were used as control subjects, and matched by gender, age, weight, and BMI. DNA damage was determined using the comet assay in the total peripheral blood. Results. The DNA damage evaluated by the comet assay revealed higher values in the group of patients with hepatitis compared with that in the control group. The relationships of the comet assay with the studied variables were assessed using multivariate analysis; significant correlations were only identified with insulin (r = 0.343, p = 0.008) and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) (r = 0.331, p = 0.011). Conclusion. Patients with genotype 1 chronic hepatitis C have higher rates of DNA damage, as determined by comet assay and this alteration is correlated with the HOMA index of insulin resistance.

DNA damage in peripheral blood cells is associated with Alzheimer's disease (AD)-related plasma proteins in individuals at risk for progression to AD

DNA damage in peripheral blood cells is associated with Alzheimer's disease (AD)-related plasma proteins in individuals at risk for progression to AD

DNA damage in peripheral blood cells is associated with Alzheimer's-related plasma proteins in individuals at risk for progression to Alzheimer's disease

DNA damage in peripheral blood cells is associated with Alzheimer's-related plasma proteins in individuals at risk for progression to Alzheimer's disease

The Micronucleus Test to Evaluate Cytogenetic Damage in Patients with Periodontitis

Background and aims. The role of genetic factors and oxidative damage in the etiopathogenesis of periodontal disease is well documented in the literature. The micronucleus test is a sensitive method that indicates DNA damage. The aim of the present study was to investigate the micronuclei frequency in different forms of periodontitis in comparison with healthy controls. Materials and methods. Micronuclei frequency was analyzed in the peripheral lymphocytes of 10 patients with chronic periodontitis (CP), 10 patients with generalized aggressive periodontitis (GAP) and 10 healthy controls. Various clinical parameters like the probing depth, clinical attachment level, and percentages of sites with bleeding and plaque were recorded. After the slides were processed, they were stained with 5% Geimsa solution and 1000 cells per sample were counted for the presence of micronuclei. Results. The mean micronuclei observed in the control group, CP group, and GAP group were 9.8, 10.1 and 9.9, respectively. The differences between the groups were not significant (P=0.978). Conclusion. The results indicated that the cytogenetic damages in the periodontitis groups were not different from those in the control group. The role of cytogenetic damage in peripheral blood cells may have a limited prognostic value in the etiopathogenesis of periodontal tissues and further studies are necessary to assess cytogenetic damage in periodontal tissues to clarify local tissue destruction in periodontal disease.

Lead (Pb) accumulation, oxidative stress and DNA damage induced by dietary Pb in tilapia (Oreochromis niloticus)

With the increasing occurrence of dietary lead (Pb) contamination in aquaculture, a better understanding of the toxic effects of dietary Pb on aquatic animals is needed. Tilapia (Oreochromis niloticus) were exposed to dietary Pb at concentrations of 0, 100, 400 and 800 μg g−1 dry weight for 60 days, and Pb accumulation in tissues and blood, oxidative stress in posterior kidney and DNA damage in peripheral blood cells were investigated. The results showed that dietary Pb exposure resulted in significant Pb accumulation in tissues and blood, which increased with the dietary Pb concentrations. Pb accumulated in sampled tissues in the following order: posterior kidney>bone>liver>gill>spleen>testis>muscle>brain. Dietary Pb caused a significant increase in the malondialdehyde level and a significant decrease in the total antioxidant capacity content when compared with the control group (P<0.05), accompanied by concentration-dependent decreases in the glutathione content, glutathione peroxidase and superoxide dismutase activities. Pb dose-dependent DNA damage was observed in peripheral blood cells of tilapia exposed to dietary Pb. The results suggest that dietary Pb exposure can induce significant Pb accumulation in tissues and blood, followed by oxidative stress in posterior kidney and DNA damage in peripheral blood cells of tilapia.

Grape juice concentrate prevents oxidative DNA damage in peripheral blood cells of rats subjected to a high-cholesterol diet

The goal of the present study was to investigate whether subchronic treatment with grape juice concentrate is able to protect liver and peripheral blood cells against cholesterol-induced injury in rats. The effects of the grape juice concentrate treatment on histopathological changes, immunohistochemistry for cyclo-oxygenase-2 (COX-2), and basal and oxidative DNA damage induced by H2O2 using a single-cell gel (comet) assay were evaluated. Male Wistar rats (n 18) were divided into three groups: group 1--negative control; group 2--cholesterol at 1 % (w/w) in their diet, treated for 5 weeks; group 3--cholesterol at 1 % in their chow, treated for 5 weeks, and grape juice concentrate at 222 mg/d in their drinking-water in the final week only. The results indicated that the treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in group 3 compared with group 2. However, grape juice concentrate was able to decrease oxidative DNA damage induced by H2O2 in peripheral blood cells, as depicted by the tail moment results. COX-2 expression in the liver did not show statistically significant differences (P>0·05) between groups. Taken together, the present results suggest that the administration of subchronic grape juice concentrate prevents oxidative DNA damage in peripheral blood cells.

Friedreich's Ataxia Induced Pluripotent Stem Cells Model Intergenerational GAA⋅TTC Triplet Repeat Instability

The inherited neurodegenerative disease Friedreich's ataxia (FRDA) is caused by GAA⋅TTC triplet repeat hyperexpansions within the first intron of the FXN gene, encoding the mitochondrial protein frataxin. Long GAA⋅TTC repeats cause heterochromatin-mediated gene silencing and loss of frataxin in affected individuals. We report the derivation of induced pluripotent stem cells (iPSCs) from FRDA patient fibroblasts by transcription factor reprogramming. FXN gene repression is maintained in the iPSCs, as are the global gene expression signatures reflecting the human disease. GAA⋅TTC repeats uniquely in FXN in the iPSCs exhibit repeat instability similar to patient families, where they expand and/or contract with discrete changes in length between generations. The mismatch repair enzyme MSH2, implicated in repeat instability in other triplet repeat diseases, is highly expressed in pluripotent cells and occupies FXN intron 1, and shRNA silencing ofMSH2 impedes repeat expansion, providing a possible molecular explanation for repeat expansion in FRDA.

Genetic damage in multiple organs of acutely exercised rats

The aim of this study was to investigate the effects of acute exercise on genomic damage in an animal model. Male adult Wistar rats were divided into the following groups: control and acute exercised (experimental). For this purpose, 15 animals were accustomed to running on a rodent treadmill for 15 min per day for 5 days (10-20 m min(-1); 08 grade). After 4 days at rest, active animals ran on the treadmill (22 m min(-1), 58 grade) till exhaustion. Cells from peripheral blood, liver, heart, and brain were collected after 0, 2, and 6 h after exercise. The results showed that acute exercise was able to induce genetic damage in peripheral blood cells after 2 and 6 h of exercise, whereas liver pointed out genetic damage for all periods evaluated. No genetic damage was induced either in brain or in heart cells. In conclusion, our results suggest that acute exercise could contribute to the genetic damage in peripheral blood and liver cells. It seems that liver is a sensitive organ to the genotoxic insult after acute exercise.