Effect of Imidocarb Application on Oxidative DNA Damage Caused by Anaplasmosis

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.

Sesamol Supplementation Mitigates Isoproterenol-Induced Cardiac Toxicity in Rats by Stabilizing Cardiac Mitochondrial and Lysosomal Enzymes

The current investigation was intended to evaluate the antimyocardial ischemic effects of sesamol on lactate dehydrogenase (LDH) isoenzymes, DNA damage, and mitochondrial and lysosomal enzyme activities in isoproterenol (ISO)-induced myocardial infarction (MI) in male albino Wistar strain rats. Rats that received ISO (85 mg/kg body weight (B.W) subcutaneously) for the first 2 consecutive days showed significant reduction in the activities of tricarboxylic acid (TCA) cycle enzymes (isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase, and succinate dehydrogenase) and respiratory chain enzymes (cytochrome c oxidase and nicotinamide adenine dinucleotide hydrogen (NADH) dehydrogenase) in the heart mitochondria. The activities of the lysosomal enzymes (α-and β-glucosidases, α and β-galactosidases, β-glucuronidase and β-N-acetyl glucosaminidase and cathepsin-B and cathepsin-D) were increased significantly in the heart homogenate of ISO-induced MI rats. ISO injection also increased the % of tail DNA, tail length, and tail moment and decreased the % of head DNA. Pretreatment with sesamol (50 mg/kg B.W) every day for a period of 9 days prevented the above abnormalities induced by ISO. In conclusion, it can be inferred that administration of sesamol has a potent beneficial role against ISO-induced damage to the mitochondria, lysosomes, and DNA, thereby preventing MI.

Environmentally Relevant Concentrations of Triclosan Induce Cyto-Genotoxicity and Biochemical Alterations in the Hatchlings of Labeo rohita

Xenobiotic Triclosan (TCS) is of great concern because of its existence in a variety of personal, household and healthcare products and continuous discharge in water worldwide. Excessive use of TCS-containing sanitizers and antiseptic products during the COVID-19 pandemic further increased its content in aquatic ecosystems. The present study deals with the cyto-genotoxic effects and biochemical alterations in the hatchlings of Labeo rohita on exposure to environmentally relevant concentrations of TCS. Three-days-old hatchlings were exposed to tap water, acetone (solvent control) and 4 environmentally relevant concentrations (6.3, 12.6, 25.2 and 60 µg/L) of TCS for 14 days and kept for a recovery period of 10 days. The significant concentration-dependent decline in cell viability but increase in micronucleated cells, nucleo-cellular abnormalities (NCAs) and DNA damage parameters like tail length, tail moment, olive tail moment and percent of tail DNA after exposure persisted till the end of recovery period. Glucose, triglycerides, cholesterol, total protein, albumin, total bilirubin, uric acid and urea (except for an increase at 60 µg/L) showed significant (p ≤ 0.05) concentration-dependent decrease after 14 days of exposure. The same trend (except for triglycerides, albumin and total bilirubin) continued till 10 days post exposure. In comparison to control, transaminases (alanine and aspartate aminotransferases) increased (p ≤ 0.05) after exposure as well as the recovery period, while a decline in alkaline phosphatase after exposure was followed by a significant increase during the recovery period. The results show that the environmentally relevant concentrations of TCS cause deleterious effects on the hatchlings of L. rohita.

Hepatic and renal cellular cytotoxic effects of heparin-coated superparamagnetic Iron oxide nanoparticles

Background Superparamagnetic iron oxide (SPIO) nanoparticles have been widely used in several biomedical engineering in vivo. Although various surface modifications have been made to these non-biodegradable nanoparticles to make them more biocompatible, their toxic potential still remains a major concern. Method In this study, we newly developed unfractionated heparin (UFH)-coated and low molecular weight heparin (LMWH)-coated SPIO nanoparticles through surface modification engineering, which was compared with commercially available dextran-coated SPIO nanoparticles. Their toxicity such as cytotoxicity, single cell gel electrophoresis (SCGE) comet assay, intracellular reactive oxygen species (ROS) content and cellular apoptosis was evaluated to hepatic HepG2 and renal HK-2 cells. Results When UFH-, LMWH- or dextran-coated SPIO nanoparticles were applied, they did not affect the viability of HepG2 cell. However, HK-2 cells were more sensitive to dextran-coated SPIO nanoparticles than others. In genotoxicity assay using SCGE comet, DNA tail moment values in the groups treated with dextran- and LMWH-coated SPIO nanoparticles significantly increased. However, UFH-coated SPIO nanoparticles was only significantly lowing DNA tail moment value. In addition, UFH-coated SPIO nanoparticles had lower cytotoxicity in HepG2 and HK-2 cells compared to dextran-coated SPIO nanoparticles, especially in terms of apoptosis and intracellular ROS production. Conclusions Collectively, it is possible that UFH- coated SPIO nanoparticles can be used as alternative negative contrast agents.

Electronic waste exposure and DNA damage: a systematic review and meta-analysis

Objectives Inappropriate processing and disposal of electronic waste (e-waste) expose workers and surrounding populations to hazardous chemicals, including clastogens and aneugens. Recently, considerable literature has grown around e-waste recycling, associated chemical exposures and intermediate health outcomes, including DNA damage. Micronuclei (MN) frequency has been widely used as a biomarker to investigate DNA damage in human populations exposed to genotoxic agents. We conducted a systematic review of published studies to assess DNA damage in e-waste-exposed populations and performed a meta-analysis to evaluate the association between e-waste exposure and DNA damage. Methods This systematic review with meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement checklist. Articles published in English from January 2000 through December 2020 investigating the associations between e-waste exposure and DNA damage were retrieved from the following three major databases: MEDLINE, ProQuest, and Scopus. Studies that reported the use of MN assay as a biomarker of DNA damage were included for meta-analysis. Studies that also reported other DNA damage biomarkers such as chromosomal aberrations, comet assay biomarkers, 8-hydroxy-2′-deoxyguanosine (8-OHdG), telomere length, apoptosis rate were reported using narrative synthesis. Results A total of 20 publications were included in this review, of which seven studies were within the occupational setting, and the remaining 13 studies were ecological studies. The review found six biomarkers of DNA damage (micronuclei, comets assay parameters (tail length, % tail DNA, tail moment, and olive tail moment), 8-OHdG, telomere length, apoptosis rate and chromosomal aberrations) which were assessed using seven different biological matrices (buccal cells, blood, umbilical cord blood, placenta, urine and semen). Most studies showed elevated levels of DNA damage biomarkers among e-waste exposed populations than in control populations. The most commonly used biomarkers were micronuclei frequency (n=9) in peripheral blood lymphocytes or buccal cells and 8-OHdG (n=7) in urine. The results of the meta-analysis showed that electronic waste recycling has contributed to an increased risk of DNA damage measured using MN frequency with a pooled estimate of the standardized mean difference (SMD) of 2.30 (95% CI: 1.36, 3.24, p<0.001) based on 865 participants. Conclusions Taken together, evidence from this systematic review with meta-analysis suggest that occupational and non-occupational exposure to e-waste processing is associated with increased risk of DNA damage measured through MN assay and other types of DNA damage biomarkers. However, more studies from other developing countries in Africa, Latin America, and South Asia are needed to confirm and increase these results’ generalizability.

Role of Yoga and Its Plausible Mechanism in the Mitigation of DNA Damage in Type-2 Diabetes: A Randomized Clinical Trial

Background Although yoga is found to be beneficial in the management of type 2 diabetes (T2D), its mechanism of action is poorly understood. T2D is also known to be associated with increased oxidative stress (OS) and DNA damage. Purpose This study examines how yoga modulates OS-induced DNA damage and the efficiency of DNA repair in T2D conditions. Methods In this assessor-masked randomized clinical trial, T2D subjects (n = 61), aged (Mean ± SD, 50.3 ± 4.2) were randomly allocated into Yoga group (31) that received 10 weeks of yoga intervention and Control (30) with routine exercises. Molecular and biochemical assessments were done before and after the intervention period. Structural Equation Modeling using “R” was used for mediation analysis. Results At the end of the 10th week, Yoga group showed significant reduction in DNA damage indicators like Tail Moment (−5.88[95%CI: −10.47 to −1.30]; P = .013) and Olive Tail Moment (−2.93[95%CI: −4.87 to −1.00]; P &lt; .01), oxidative DNA damage marker 8-OHdG (−60.39[95%CI: −92.55 to −28.23]; P &lt; .001) and Fasting Blood Sugar (-22.58[95%CI: −44.33 to −0.83]; P = .042) compared to Control. OGG1 protein expression indicating DNA repair, improved significantly (17.55[95%CI:1.37 to 33.73]; P = .034) whereas Total Antioxidant Capacity did not (5.80[95%CI: -0.86 to 12.47]; P = 0.086). Mediation analysis indicated that improvements in oxidative DNA damage and DNA repair together played a major mediatory role (97.4%) in carrying the effect of yoga. Conclusion The beneficial effect of yoga on DNA damage in T2D subjects was found to be mediated by mitigation of oxidative DNA damage and enhancement of DNA repair. Clinical Trial information (www.ctri.nic.in) CTRI/2018/07/014825

Genomic Damage Induced in Nicotiana tabacum L. Plants by Colloidal Solution with Silver and Gold Nanoparticles

Tobacco seedlings (Nicotiana tabacum L cv. Wisconsin 38) were treated for 24 h with colloidal solution of silver and gold nanoparticles (AgNPs and AuNPs) of different size or cultivated for 8 weeks on soil polluted with these NPs. DNA damage in leaf and roots nuclei was evaluated by the comet assay. AgNPs of the size 22–25 nm at concentrations higher than 50 mg·L−1 significantly increased the tail moments (TM) values in leaf nuclei compared to the negative control. Ag nanoparticles of smaller size 12–15 nm caused a slight increase in tail moment without significant difference from the negative control. The opposite effect of AgNPs was observed on roots. The increasing tail moment was registered for smaller NPs. Similar results were observed for AuNPs at a concentration of 100 mg·L−1. DNA damaging effects after growing tobacco plants for 8 weeks in soil polluted with AgNPs and AuNPs of different size and concentrations were observed. While lower concentrations of both types of particles had no effect on the integrity of DNA, concentration of 30 mg·kg−1 of AgNPs caused significant DNA damage in leaves of tobacco plants. AuNPs had no effect even at the highest concentration. The content of Ag was determined by ICP–MS in above-ground part of plants (leaves) after 8 weeks of growth in soil with 30 mg·kg−1.AgNPs and was 2.720 ± 0.408 µg·g−1. Long term effect is much less harmful probably due to the plant restoration capability.

In vitro toxicological assessment of flumethrin’s effects on MCF-7 breast cancer cells

Pyrethroid pesticides are frequently used for household insect control of insects and in agriculture and livestock. Flumethrin is a pyrethroid that is used against ectoparasites in many animals. The goal of this study was to evaluate the cytotoxic, apoptotic, genotoxic, and estrogenic effects of flumethrin on the mammalian breast cancer cell line (MCF-7). Compared with control groups, a dose-dependent decrease was observed in cell viability at concentrations of 100 µM and higher. The cytotoxic and apoptotic effects detected by LDH assay and AO/EtBr staining increased significantly at a concentration of 1000 µM. The expression of BCL2, which is an anti-apoptotic gene, significantly decreased, whereas BAX, TP53, and P21 expression significantly increased. The results of a comet assay indicated that flumethrin significantly changed tail length, tail % DNA, tail moment, and Olive tail moment in concentrations above 1 and 10 µM. In addition, a 0.1 µM concentration of flumethrin affected ERα receptor mediated cell proliferation and increased transcription of estrogen-responsive pS2 (TFF1) and progesterone receptor (PGR) genes. As a result, flumethrin-induced apoptosis and cytotoxicity at a high concentration, while induced genotoxicity even at lower concentrations. Flumethrin is an endocrine disrupting insecticide with estrogenic effects at very low concentrations.

Assessment of Cytogenetic Damage and Cholinesterases’ Activity in Workers Occupationally Exposed to Pesticides in Zamora-Jacona, Michoacan, Mexico

Pesticides have been considered as potential chemical mutagens; however, little is known about toxic and genotoxic effects during pesticide application in Zamora-Jacona, Michoacan State in Mexico. This study sought to determine DNA damage and cholinesterase activities inhibitions in 54 agricultural workers exposed to complex mixtures of pesticides vs. control group (26 individuals) using Comet assay in peripheral whole blood, micronucleus (MN) test in oral mucosa cells, Cytokinesis-blocked MN assay in lymphocytes (L-CBMNcyt) and measuring AChE and BChE activities in whole blood and plasma samples, respectively. Exposed subjects demonstrated significantly elevated levels of primary (Comet assay: tail intensity, tail length, tail moment, Olive tail moment) and permanent DNA damage (MN assay: in blood/buccal cells; frequencies of nuclear buds, binucleated cells, cells with condensed chromatin, karyorrhexis, pyknosis, and karyolysis). However, inhibition of cholinesterase activities (AChE and BChE) was not observed in the workers. Confounding factors including sex, age, BMI, working exposure period, protection level, smoking habit (cigarettes per day units), alcohol consumption (weekly), medication, were considered in the analysis. These combined techniques demonstrated usefulness in the health hazards risks pesticide exposure assessment and suggested the need for periodic monitoring together with the education and the training of occupational workers for the safe application of potentially harmful pesticides.

Genomic markers for the biological responses of Triclosan stressed hatchlings of Labeo rohita

Triclosan (TCS) used commonly in pharmaceuticals and personal care products has become the most common pollutant in water. Three days old hatchlings of an indegenous fish, Labeo rohita were given 96h exposure to an environmentally relevant (0.06mg/L) and two moderately lethal concentrations (0.067 and 0.097 mg/L) of TCS and kept for 10 days of recovery for recording transcriptomic alterations in antioxidant/detoxification (SOD, GST, CAT, GPx, GR, CYP1a and CYP3a), metabolic (LDH, ALT and AST) and neurological (AchE) genes and DNA damage. The data were subjected to Principal Component Analysis (PCA) for obtaining biomarkers for the toxicity of TCS. Hatchlings were highly sensitive to TCS (96h LC 50 = 0.126mg/L and risk quotient = 40.95), 96h exposure caused significant induction of CYP3a, AChE and ALT but suppression of all other genes. However, expression of all the genes increased significantly (except for a significant decline in ALT) after recovery. Concentration dependent increase was also observed in DNA damage [Tail Length (TL), Tail Moment (TM), Olive Tail Moment (OTM) and Percent Tail DNA (TDNA)] after 96h. The damage declined significantly over 96h values at 0.06 and 0.067 mg/L after recovery, but was still several times more than control. TCS elicited genomic alterations resulted in 5-11% mortality of exposed hatchlings during the recovery period. It is evident that hatchlings of L. rohita are a potential model and PCA shows that OTM, TL, TM, TDNA, SOD and GR (association with PC1 during exposure and recovery) are the biomarkers for the toxicity of TCS.