Genotoxicity Stress Research Articles

Genotoxicity, oxidative stress, and inflammatory response induced by crack-cocaine: relevance to carcinogenesis.

Crack-cocaine is a cocaine by-product widely consumed by general population in developing countries. The drug is low cost and is associated with more intense effects when compared to other illicit drugs. Genotoxicity, oxidative stress, and inflammatory response are considered crucial events in carcinogenesis, since they actively participate in the multistep process. The purpose of this paper was to provide a mini review regarding the relationship between carcinogenesis and genotoxicity, oxidative stress, and inflammation induced by crack-cocaine. The present study was conducted on search of the scientific literature from the published studies available in PubMed, MEDLINE, Scopus, and Google Scholar for all kind of articles (all publications to November 2020) using the following key words: crack-cocaine, DNA damage, genotoxicity, cellular death, cytotoxicity, mutation, oxidative stress, inflammation, and mutagenicity. The results showed that published papers available were almost all in vivo test system being conducted in humans or rodents. Crack-cocaine was able to induce genotoxicity and oxidative stress in mammalian cells. However, the role of inflammatory response after exposure to crack-cocaine was not conclusive so far. In summary, this study is consistent with the notion that crack-cocaine is a chemical carcinogen as a result of genotoxicity and oxidative stress induced in mammalian and non-mammalian cells.

Impact of 12-month cryopreservation on endogenous DNA damage in whole blood and isolated mononuclear cells evaluated by the comet assay

The comet assay is an electrophoretic technique used to assess DNA damage, as a marker of genotoxicity and oxidative stress, in tissues and biological samples including peripheral blood mononuclear cells (PBMCs) and whole blood (WB). Although numerous studies are performed on stored samples, the impact of cryopreservation on artifactual formation of DNA damage is not widely considered. The present study aims to evaluate the impact of storage at different time-points on the levels of strand breaks (SBs) and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites in isolated PBMCs and WB. Samples were collected, aliquoted and stored at − 80 °C. DNA damage was analyzed on fresh samples, and subsequently on frozen samples every 2 months up to a year. Results have shown no changes in DNA damage in samples of PBMCs and WB stored for up to 4 months, while a significant increase in SBs and Fpg-sensitive sites was documented starting from 6-month up to 12-month storage of both the samples. In addition, fresh and frozen WB showed higher basal levels of DNA damage compared to PBMCs. In conclusion, WB samples show high levels of DNA damage compared to PBMCs. One-year of storage increased the levels of SBs and Fpg-sensitive sites especially in the WB samples. Based on these findings, the use of short storage times and PBMCs should be preferred because of low background level of DNA damage in the comet assay.

In vivo antigenotoxic potential of sesame oil against cyclophosphamide induced genotoxicity and oxidative stress in mice

In vivo antigenotoxic potential of sesame oil against cyclophosphamide induced genotoxicity and oxidative stress in mice

Investigating the underlying mechanism of cadmium-induced plant adaptive response to genotoxic stress

Plants as sessile organisms have developed some unique strategies to withstand environmental stress and adaptive response (AR) is one of them. In the present study Cadmium (Cd)-induced AR was evaluated to ameliorate the genotoxicity of a known chemical mutagen ethyl methanesulphonate (EMS) based on cytotoxicity, genotoxicity and oxidative stress in two model plant systems Allium cepa L. and Vicia faba L. Priming the plants with cadmium chloride (CdCl2, 25 and 50 μM) reduced the genotoxicity of EMS (0.25 mM). Cd-induced AR was evident by the magnitude of adaptive response (MAR) values calculated for cytotoxicity, genotoxicity and biochemical parameters. In addition the involvement of some major metabolic pathways and epigenetic modifications in AR was investigated. Metabolic blockers of protein kinase cascades, DNA repair, oxidative stress and de novo translation interfered with the adaptive response implying their role in AR whereas, inhibitors involved in post-replication repair and autophagy were ineffective implicating that they probably have no role in the AR studied. Moreover to find the role of DNA methylation in AR, methylation-sensitive comet assay was carried out. Simultaneously 5-methyl- 2'-deoxycytidine (5mdC) levels were quantified by HPLC (high performance liquid chromatography). AR was eliminated in cells treated with a demethylating agent, 5-aza- 2'deoxycytidine (AZA). Results implied a contribution of DNA hypermethylation. To the best of our knowledge this is a first report correlating DNA methylation to Cd-induced adaptive response in plants undergoing genotoxic stress.

Dose-independent genotoxic response in A549 cell line exposed to fungicide Iprodione.

The fungicide Iprodione is widely applied in vegetables and raises concern for human health. The A549 human lung carcinoma cell line is a suitable model for assessing the toxicological effects of drugs. The goal of this work was to evaluate the genotoxicity and oxidative stress in the A549 cell line exposed to sublethal concentrations from 3 to 100µg/mL Iprodione considering LC50 = 243.4µg/mL Iprodione, as determined by the MTT assay. Generalized Linear Mixed Models (GLMM) were performed to determine the association between the responses NDI, MNim and MNib and the explanatory variables. Iprodione and solvent were relativized to the control whereas the concentration was included as numeric variable. ANOVA was used for the comparison of treatments. The coefficients of linear association between the explanatory variables and NDI, and the coefficients of logistic association between explanatory variables and MNim were not significant. However, these coefficients showed significant association with MNib only for Iprodione treatment but not for Iprodione concentration, indicating lack of dose-response relationship. Genotoxicity risk assessment indicated that the increase in Iprodione concentrations increased slightly the probability of belonging to the genotoxic category. ANOVA showed significant differences in MNib, and non-significant differences in NDI and MNim among treatments. The oxidative stress analysis performed at 3, 12, and 25μg/mL Iprodione showed a significant and linear increase in SOD, and a significant and linear decrease in GSH and GST. The Dunnett test was significant for GSH at 12 and SOD at 25μg/mL.

PROTECTIVE EFFECT OF VITAMIN C ON LEACHATE INDUCED GENOTOXICITY AND OXIDATIVE STRESS IN THE LIVER AND OVARY OF RAT

IntroductionThis study investigated the protective effect of vitamin C on leachate induced genotoxicity and oxidative stress in the liver and ovary of rats exposed to Ajakanga landfill leachate. Methods Sixty female rats(150-200g) were equally divided into ten groups(A-I). Group A animals(control) were given distilled water, groups B – E animals were given 12.5%, 25%, 50%, and 100% leachate respectively via drinking water for twenty-eight days. Animals in group F were given distilled water plus 100mg/kg vitamin C while groups G – I animals were given 100mg/kg vitamin C plus 12.5%, 25%, 50%, and 100% leachate respectively. Activities of alanine amino transferase(ALT), aspartate aminotransferase(AST) and Gamma-glutamyltransferase(GGT) were determined in the serum of rats using enzyme kits. Oxidative stress markers were determined in the liver and ovary of the rats by spectrophotometry. Genotoxicity study was carried out using micronucleus assay.Results There was increase in the activities of ALT, AST and GGT in serum of rats exposed to leachate compared with control but ALT and AST activity decreased in rats treated with vitamin C. There was increase in malondialdehyde concentration (index of lipid peroxidation) in the liver (102.3-302.7mol/mg protein) and ovary (1.1-2.1mol/mg protein) of rats exposed to leachate compared with control (72.6mol/mg protein;0.7mol/mg protein) but there was a significant decrease in animals treated with vitamin C. There was decrease in the levels of reduced glutathione and super oxide dismutase in the ovary of rats in groups B-E, but vitamin C treatment increased the levels of these antioxidants. A significant increase in micronucleated polychromatic erythrocytes(MPCE) was observed in bone marrow of rats exposed to leachate (74.7-113 MPCE/1000PCE) but there was a decrease in MPCEs in rats treated with vitamin C (66.8-78.8 MPCE/1000PCE).Conclusion Vitamin C has a protective effect on leachate induced genotoxicity and oxidative stress in the liver and ovary of the rats.

Pesticide exposure and health effects in Latin American and the Caribbean populations: A systematic review.

Background: Growing evidence suggests that exposure to pesticides may be associated with adverse health effects in different population groups, including farmworkers, pregnant women, and children. However, data on the current state of research on this topic in the Latin American and the Caribbean (LAC) region are scarce. We examined the available epidemiological literature on the health effects of pesticide exposure in LAC populations, with the goal of identifying knowledge gaps and capacity building needs. Methods: We searched PubMed and SciELO for epidemiological studies on environmental and/or occupational pesticide exposure and human health in LAC populations published between January 2007 and March 2019. Ultimately, 137 papers from 13 countries were selected and grouped by health outcome (genotoxicity and oxidative stress, neurotoxicity, placental effects and teratogenicity, cancer, endocrine disruption, reproductive health, and others). Results: Most papers (87%) reported associations of pesticide exposure with at least one of the health outcomes. The most frequently studied health effects included genotoxic and oxidative damage (26%), neurotoxicity (19%), and endocrine disruption (10%). Most published studies were conducted in Brazil (40%) and Mexico (23%), were primarily cross-sectional in design (75%), and examined farmworkers (42%) and children (22%). About half of the published studies used direct methods to assess exposure (e.g., exposure biomarkers; 47%) and were rated as high or intermediate-high quality (44%). Conclusion: Despite the small number of published studies and their limitations, our review suggests that pesticides are associated with adverse health outcomes among occupationally and/or environmentally exposed populations. Additional research would allow a better understanding of the potential health effects of pesticides in LAC populations and would help to identify effective intervention. An integration of research initiatives that bridge multiple disciplines and the establishment a regional network of researchers would also help address existing knowledge gaps and capacity building needs.

In-vitro evaluation of a partially biodegradable TiMg dental implant: The cytotoxicity, genotoxicity, and oxidative stress

The aim of this study was to evaluate the In-vitro response, including cytotoxicity, genotoxicity, and oxidative stress, of a pretreated dental implant (DI) that was produced from a novel partially biodegradable Ti17Mg composite material. Viability and adhesion, and morphological alteration of Mouse fibroblast NCTC clone 929 cell line (L929) and human Dental Pulp Stem Cells (hDPSCs) were evaluated using MTT and live/dead assays. The genotoxic potential was investigated by comet and plasmid DNA interaction assays. The oxygen reactive species (ROS) formation was detected by Oxidative stress testing. The results showed surface pretreatment by 20 h prewashing in Hank's balanced salt solution (HBSS) at 20 mL.cm−2 concertation minimized the hypermagnesemia effect. Compared with the Ti Grade 4 (TiGR4) reference EDS analysis confirmed formation of a Ca/P-rich biomimetic layer on the surface of Ti17Mg DI after extraction in DMEM. The indirect MTT assay revealed that Ti17Mg DI extracts exerted a mild level of cytotoxicity without any induced morphological alteration of the incubated cells. The direct assays showed that the initial cell adhesion and proliferation were improved. No DNA damage was induced by Ti17Mg DI. No detection for smearing or loss of plasmid DNA was found. Oxidative stress confirmed no increase in ROS levels. In-vitro evaluation study confirmed a desirable In-vitro response of pretreated Ti17Mg that was comparable to that of the TiGR4 reference. The obtained results suggest the Ti17Mg composite exhibits a promising application potential as a material for the fabrication of DI.

Women rag pickers at a dump in Ahmedabad: Genotoxicity and oxidative stress

Municipal solid waste (MSW) generated in Ahmedabad, India, and the surrounding area is dumped at the Pirana site; rag pickers collect materials for re-sale. We have compared genotoxicity and oxidative stress in samples from women rag pickers working at this site, with women involved only in door-to-door waste picking (in residential areas near the university campus) as “controls”. The buccal Cytokinesis-Block Micronucleus (CBMN) assay showed significantly higher frequencies of Micronucleus (MN), Nucleoplasmic Bridges (NPB), and Nuclear Buds (NB) in the rag pickers than in the “controls”. The buccal Micronuclei Cytome (BMCyt) assay showed significantly higher prevalence of nuclear anomalies, such as micronucleus, karyorrhexis, karyolytic cells, and nuclear buds. Blood samples from the rag pickers showed lower levels of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), lower total serum protein concentrations, and greater lipid peroxidation compared to the “control” group. Exposure to hazardous solid waste may lead to increased oxidative damage and genotoxicity; improved safety procedures and the use of personal protective equipment are recommended.

Genotoxicity and Oxidative Stress Evaluations in Juvenile African Catfish Clarias gariepinus Exposed to NPK Fertilizer.

Juvenile African Catfish (also known as Sharptooth Catfish) Clarias gariepinus were exposed to 2.26, 4.52, and 11.30mg/L NPK (15-15-15) fertilizer for 21d followed by 7d of recovery to assess the genotoxic effects of the fertilizer in erythrocytes. Biomarkers of oxidative stress were evaluated in the liver and gill tissues. The fertilizer induced micronuclei formation with maximum effects on day 7 in erythrocytes of individuals that were exposed to 4.52 and 11.30mg/L NPK, and on day 14 in individuals exposed to 2.26mg/L of the same fertilizer. The lipid peroxidation, glutathione reductase, and reduced glutathione values in the exposed fish increased, while the values of catalase, superoxide dismutase, and glutathione peroxidase decreased. There were mixed trends in the recovery patterns after the 7-d withdrawal from the fertilizer. Careful use of the fertilizer in the field is recommended to avoid toxicological effects on nontarget organisms.

Pooled analysis of genotoxicity markers in relation to exposure in the Flemish Environment and Health Studies (FLEHS) between 1999 and 2018

BackgroundThe Flemish Environment and Health Studies (FLEHS) are human biomonitoring surveys running in Flanders since 1999. Additionally to biomarkers of exposure, markers of genotoxicity and oxidative stress have been measured, including the alkaline comet and micronucleus assay in peripheral whole blood cells, and urinary concentrations of 8-oxo-2′-deoxyguanosine (8-oxodG). AimExposure-effect associations were explored in a pooled dataset of nine different cross-sectional FLEHS surveys. Data of adolescents collected in a time frame of about 20 years (1999–2018) were compiled. The aim of the study was to examine whether increased variation in exposure, lifestyle and environmental factors would lead to more powerful and robust exposure-effect associations. Materials & methodsThe biomarkers were measured in 2283 adolescents in the age range of 14–18 years. Exposure to polycyclic aromatic hydrocarbons [1-hydroxypyrene (1-OHP)], benzene (tt’-muconic acid), metals (arsenic, cadmium, copper, nickel, thallium, lead, chromium), persistent organochlorines and phthalates were assessed in blood or urine. Furthermore, outdoor air levels of particulate matter (PM10 and PM2.5) at the residences of the youngsters were calculated. Pooled statistical analysis was done using mixed models. Study-specific differences in the genotoxicity markers and in the strength/direction of the association were accounted for. This was done by incorporating the random factor ‘study’ and a random study slope (if possible). The exposure markers were centered around the study-specific mean in order to correct for protocol changes over time. ResultsA significant association was observed for the urinary oxidative stress marker 8-oxodG, which was positively associated with 1-OHP (5% increase for doubling of 1-OHP levels, p = 0.001), and with urinary copper (26% increase for doubling of copper levels, p = 0.001), a metal involved in the Fenton reaction in biological systems. 8-oxodG was also associated with the sum of the metabolites of the phthalate di(2-ethylhexyl) phthalate (DEHP) (3% increase for doubling of the DEHP levels, p = 0.02). For those associations, data pooling increased the statistical power. However, some of the associations in the individual surveys, were not confirmed in the pooled analysis (such as comet assay and 8-oxodG vs. atmospheric PM; and 8-oxodG vs. urinary nickel). This may be due to inconsistencies in exposure-effect relations and/or variations in the pollutant mix over time and regions. ConclusionPooled analysis including a large population of 2283 Flemish adolescents showed that 8-oxodG, a marker of oxidative DNA damage is a valuable marker to assess impact of daily life pollutants, such as PAHs, Cu and the phthalate DEHP.

Determination of protective effect of carob (Ceratonia siliqua L.) extract against cobalt(II) nitrate-induced toxicity.

Cobalt (Co) is widely used in many industrial fields such as batteries and paints. Cobalt, a dangerous heavy metal, can be found in high concentrations in natural and human habitats. Although cobalt is an important micronutrient, it is toxic to living organisms when exposed to high amounts. Carob (Ceratonia siliqua L.) is a tree native to The Mediterranean region. Carob bean, which has high nutritional and economic value, is used against cardiovascular and gastrointestinal diseases. In addition, the antioxidant properties of carob are gaining importance in recent years. In this study, the protective effects of carob extract against the toxicity of cobalt on Allium cepa L. were investigated. For this purpose, 150mg/L and 300mg/L carob extract solutions and 5.5mg/kg cobalt solutions were applied to A. cepa L. bulbs. Root emergence, weight gain, root elongation, and mitotic index (MI) decreased, while the frequency of chromosomal abnormalities (CAs) and micronucleus (MN) increased as a result of Co application. Furthermore, Co treatment triggered a noticeable rise in the activities of superoxide dismutase (SOD) and catalase (CAT) enzymes as well as the malondialdehyde (MDA) amount and the abnormalities in the meristematic cells. On the other hand, applications of carob extracts mitigated cobalt-induced damages in a dose-dependent manner in all parameters. Therefore, the current study showed that the strong preventive potential of carob extract against phytotoxicity and genotoxicity is caused by Co in a model plant. The protective effects of carob extract on Co-induced toxicity were demonstrated for the first time in terms of reducing genotoxicity and oxidative stress response.

A chemical, microbiological and (eco)toxicological scheme to understand the efficiency of UV-C/H2O2 oxidation on antibiotic-related microcontaminants in treated urban wastewater

An assessment comprising chemical, microbiological and (eco)toxicological parameters of antibiotic-related microcontaminants, during the application of UV-C/H2O2 oxidation in secondary-treated urban wastewater, is presented. The process was investigated at bench scale under different oxidant doses (0–50 mg L−1) with regard to its capacity to degrade a mixture of antibiotics (i.e. ampicillin, clarithromycin, erythromycin, ofloxacin, sulfamethoxazole, tetracycline and trimethoprim) with an initial individual concentration of 100 μg L−1. The process was optimized with respect to the oxidant dose. Under the optimum conditions, the inactivation of selected bacteria and antibiotic resistant bacteria (ARB) (i.e. faecal coliforms, Enterococcus spp., Pseudomonasaeruginosa and total heterotrophs), and the reduction of the abundance of selected antibiotic resistance genes (ARGs) (e.g. blaOXA, qnrS, sul1, tetM) were investigated. Also, phytotoxicity against three plant species, ecotoxicity against Daphnia magna, genotoxicity, oxidative stress and cytotoxicity were assessed.Apart from chemical actinometry, computational fluid dynamics (CFD) modelling was applied to estimate the fluence rate. For the given wastewater quality and photoreactor type used, 40 mg L−1 H2O2 were required for the complete degradation of the studied antibiotics after 18.9 J cm−2. Total bacteria and ARB inactivation was observed at UV doses <1.5 J cm−2 with no bacterial regrowth being observed after 24 h. The abundance of most ARGs was reduced at 16 J cm−2. The process produced a final effluent with lower phytotoxicity compared to the untreated wastewater. The toxicity against Daphnia magna was shown to increase during the chemical oxidation. Although genotoxicity and oxidative stress fluctuated during the treatment, the latter led to the removal of these effects. Overall, it was made apparent from the high UV fluence required, that the particular reactor although extensively used in similar studies, it does not utilize efficiently the incident radiation and thus, seems not to be suitable for this kind of studies.

CHITOSAN NANOPARTICLES SUPPRESS THE OXIDATIVE STRESS IN SUBMANDIBULAR SALIVARY GLANDS AND PREVENT THE GENOTOXICITY OF MONOSODIUM GLUTAMATE IN ALBINO RATS: HISTOLOGICAL, IMMUNOHISTOCHEMICAL AND CHROMOSOMAL ABERRATIONS ANALYSIS STUDY

Aim of the study: The goal of the current study was to evaluate the protective impact of chitosan nanoparticles (COS-NPs) against monosodium glutamate (MSG)-induced oxidative stress in submandibular salivary glands and genotoxicity of bone marrow chromosomes. Material and methods: 30 adult male albino rats were randomly divided into three equal groups and treated orally for 24 days as follow: Group I the (control) group, group II (MSG-treated group): each rat received a daily MSG at a dose of (400mg/Kg. b. w.) and group III: (MSG + COS-NPs treated group): rats treated orally with monosodium glutamate (400 mg/kg. b. w.) then the chitosan nanoparticles (280 mg/kg b. w.) respectively was administered to rats daily by oral gavage. After 24 days, both sides of the submandibular salivary glands were excised, processed and finally inspected histologically and immunohistochemically. Bone marrow was obtained from both femora of rats, 500 well spread metaphases per each animal were checked microscopically for both structural and numerical chromosomal aberrations. Results: The submandibular salivary glands (SMSG) of MSG treated rats revealed severe histopathological changes, moderate to strong granular cytoplasmic reaction of caspase-3 immunoreactivity in the acinar and ductal cells. And increase in the frequency of structural and numerical chromosomal aberrations of bone marrow cells. Chitosan nanoparticles (COSNPs) exhibited significant amelioration in histological and immunohistochemical picture in the submandibular salivary glands of MSG treated rats. Also chitosan nanoparticles could significantly inhibit the chromosomal aberrations and succeeded to neutralize the MSG genotoxic effects in bone marrow cells of rats. Conclusion: It could be concluded that COS-NPs have potential antioxidant effect that protect against cytotoxicity and genotoxicity induced by MSG in rats.

An engineered non-erythropoietic erythropoietin-derived peptide, ARA290, attenuates doxorubicin induced genotoxicity and oxidative stress

Erythropoietin (EPO) applies anti-inflammatory, anti-apoptotic, anti-oxidant and cytoprotective effects besides its hematopoietic action. A nonhematopoietic peptide engineered from EPO, ARA 290, interacts selectively with the innate repair receptor and has similar possessions. ARA290 mediates tissue protection without hematopoietic side-effects of EPO which limit its clinical application. Doxorubicin (DOX) is the broad-spectrum chemotherapeutic agent, but its use is limited by the development of nonspecific toxicity on noncancerous tissues especially in cardiac cells. Mechanisms behind the DOX-induced toxicities are enhanced level of oxidative damage, inflammation and apoptosis. In the present study, we have investigated whether ARA290 acts as a chemoprotective agent modulating the cytotoxicity, genotoxicity and oxidative stress induced in vitro by DOX. The genoprotective effect of ARA290 on DOX-induced toxicity in three cell line (HepG2, HGF & Stem cell) were assessed. Cells were treated with ARA290 (50–400 nM) and DOX (1 μM) in pretreatment condition. Cytotoxicity was evaluated using the MTT assay, genoprotective effect of ARA290 were evaluated using the micronucleus test and comet assay. AR290 significantly reduced the percentage of DNA in tail and the frequency of micronuclei induced by DOX. Besides, DOX impaired anti-oxidant defense enzyme activities and induced inflammation and apoptotic cell death. ARA290 markedly attenuated DOX induced oxidative stress and protected against DOX induced inflammation and apoptotic cell death. This result proposes that ARA290 can act as a protective agent, reducing DOX-induced DNA damage and oxidative stress, and it is possible that this protection could also extend to cardiac cells.

Genotoxicity and Oxidative Stress in Experimental Hybrid Catfish Exposed to Heavy Metals in a Municipal Landfill Reservoir.

This study aimed to investigate the concentrations of Cr, Cd and Pb in the water, sediment and experimental hybrid catfish muscles, and to compare the genetic differentiation and the levels of oxidative stress biomarkers (malondialdehyde and protein carbonyl) between the catfish from the contaminated reservoir near a municipal landfill and the reference area after chronic exposure. The concentrations of all metals in the water and the concentration of Cd in the sediment exceeded Thailand’s surface water quality and soil quality standards, respectively, whereas the concentrations of these metals in fish muscles did not exceed Thailand’s food quality standards. Dendrogram results in terms of genetic similarity values of the catfish from the reference and the landfill areas were 0.90 to 0.96 and 0.79 to 0.86, respectively, implying that the genetic differentiation of the fish from the landfill was greater than of those from the reference area. The fish in the landfill reservoir had slightly increased protein carbonyl levels. The results indicate that chronic heavy metal exposure can cause genotoxicity of the hybrid catfish and induce protein carbonyl as an oxidative stress biomarker in the reservoir near a municipal landfill.

Genotoxicity and oxidative stress in Caiman latirostris hatchlings exposed to pesticide formulations and their mixtures during incubation period.

Agricultural expansion and the consequent use of pesticides lead to the loss and fragmentation of natural habitats of several wild species. Then, many species are inevitably exposed to a wide amount of pesticide formulations. Glyphosate (GLY)-based formulations are the most used herbicide, whereas two of the most employed insecticides are chlorpyrifos (CPF) and cypermethrin (CYP). The aim of this study was to evaluate genotoxicity, oxidative damage, and the modulation of antioxidants defenses in peripheral blood of Caiman latirostris after embryonic exposure to pesticide formulations and their mixtures. Pesticides concentrations employed were equivalent to those recommended in agricultural practices for application in soybean crops and a half of them: GLY: 2% and 1%; CYP: 0.12% and 0.06%; CPF: 0.8% and 0.4%. Two similar experiments (E1 and E2) were carried out in consecutive years, where C. latirostris eggs were exposed to pesticide formulations separately and in different mixtures through application on the incubation material. After hatching, blood samples were taken and genotoxicity and oxidative stress was evaluated through the micronucleus (MN) test, the modified comet assay, the lipid peroxidation (LPO) levels and the activities of catalase (CAT) and superoxide dismutase (SOD) antioxidant enzymes. The results indicated the presence of DNA damage, oxidation of purines and pyrimidines, and increased frequency of micronucleus (FMN) in the case of GLY, CYP, and CPF formulations exposure, as well as in all the mixtures tested, with respect to the control groups. Specifically, the results observed for the mixtures would indicate independent action or antagonism of the components for DNA damage and base oxidation (purines and pyrimidines) and a possible potentiation interaction for the FMN in two binary mixtures. However, there were not differences regarding lipid peroxidation, the activity of antioxidant enzymes and growth parameters. This study proved that the use of pesticide formulations at concentrations used in the field generate deleterious genetic effects on this species, then, exposure to them could threaten its survival and health status.

Aluminium Induced DNA-damage and Oxidative Stress in Cultures of the Marine Sponge Hymeniacidon perlevis

Aluminium is the most abundant element in the earth crust, and has no known biological function. However, it is an established neurotoxicant in its trivalent oxidation state, with exposure resulting in neurodegenerative diseases like Parkinson’s disease and presenile dementia. Although, the potential genotoxic and carcinogenic effects of aluminium are established in mammalian and other model system, there is however very limited information on aluminium genotoxicity in aquatic invertebrates. Mechanism of aluminium toxicity is also largely unclear. With a concentration range between 0.001– 0.05mg/L in near neutral pH water, and up to 0.5-1mg/L in an acidic water , aluminium poses a potential threat to the marine ecosystem, however it is poorly studied. This study, therefore presents for the first time, aluminium-induced DNA damage using the comet assay and reactive oxygen Species (ROS) formation using 2’, 7’-dichlorodihydrofluorescein diacetate (H2DCF-DA) assay as biomarkers of genotoxicity and oxidative stress in the inter-tidal marine sponge Hymeniacidon perlevis, respectively. H. perlevis is widely distributed in the British Isles, Mediterranean and the Arctic sea and has been reported as a model for environmental biomonitoring in aquatic ecosystem and as a suitable alternative to bivalves. In this study, cryopreserved single sponge cells of H. perlevis were cultured as viable aggregates and were thereafter treated with 0.1, 0.2, 0.3 and 0.4mg/L aluminium chloride (AlCl3) for 12 hours. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Our results showed that non-cytotoxic concentrations of AlCl3 caused a statistically significant concentration-dependent increase in the level of DNA-strand break and reactive oxygen species formation single sponge cells of H. perlevis. There was also a statistically significant positive linear correlation between aluminium-induced DNA strand break and ROS formation suggesting the involvement of ROS in the causative mechanism of the aluminium induced DNA-strand breaks observed.

Chenopodium murale essential oil alleviates the genotoxicity and oxidative stress of silver nanoparticles in the rat kidney

This study aimed to synthesize AgNPs using Chenopodium murale extract (CME), to evaluate the antioxidant activity of the Chenopodium murale essential oil (CMEO) and the protective role against nephrotoxicity of AgNPs. Seven groups of female Sprague-Dawley rats were treated orally for 21 days included the control group, AgNPs-treated groups (25 or 50 mg/kg b.w), CMEO-treated groups (0.5 or 1 mg/kg b.w) and AgNPs plus CMEO-treated groups. The synthesized AgNPs were 30-50 nm in size. CMEO is rich in total phenolic and flavoniods and showed high antioxidant and radicals scavenging activity in vitro. AgNPs disturbed kidney function, decreased the antioxidant enzymes, increased serum electrolytes, TNF-α, MDA and NO, up-regulated Bcl-2, down-regulated Bax and P53 and induced histological changes in kidney tissue. CMEO protected the kidney against AgNPs toxicity in a dose-dependent manner. It could be concluded that AgNPs induced cytotoxicity and oxidative stress in the kidney. CMEO overcomes the nephrotoxicity and should be considered as a supplement to protect the kidney against oxidative stress.

Genotoxicity and biocompatibility of superparamagnetic iron oxide nanoparticles: Influence of surface modification on biodistribution, retention, DNA damage and oxidative stress

Superparamagnetic iron oxide nanoparticles (SPION) require stable surface modifications to render safe nanocapsules for biomedical applications. Herein, two types of surface modified poly(lactic-co-glycolic acid)-encapsulated SPION were synthesized using either α-tocopheryl-polyetheleneglycol-succinate (TPGS) or didodecyl-dimethyl-ammonium-bromide (DMAB) as surfactants by emulsification. SPION-TPGS (180 nm) was larger than SPION-DMAB (25 nm) and uncoated SPION (10 nm). Both formulations were positively charged and induced lower cyto-genotoxicity and ROS generation than uncoated SPION in human lymphocytes. SPION-DMAB was least cyto-genotoxic among the three. Based on these results, mice were gavaged with the formulations for 5 consecutive days and biocompatibility studies were performed on the 7th and 21st days. ICP-AES and Prussian blue staining revealed the internalization of SPION-DMAB in brain and spleen, and SPION-TPGS in liver and kidney on day 7. This was correlated with high DNA damage and oxidative stress in the same organs. Substantial clearance of Fe was accompanied by reduced genotoxicity and oxidative stress on day 21. Therefore, SPION-DMAB can be further studied for oral drug delivery to the brain and imaging of cerebral tissue without any functional ligand or external magnetic field.