Genotoxic effects in the Eastern mudminnow (Umbra pygmaea) after prolonged exposure to River Rhine water, as assessed by use of the in vivo SCE and Comet assays

2012 ◽  
Vol 53 (4) ◽  
pp. 304-310 ◽  
Author(s):  
E.J.M. Penders ◽  
A. Spenkelink ◽  
W. Hoogenboezem ◽  
S.G.P. Rotteveel ◽  
J.L. Maas ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
River Rhine ◽  
Genotoxic Effects ◽  
Rhine Water

Glial cytotoxicity of low doses of cadmium as a model of heavy metal pollution influence on vertebrates

2020 ◽  
Vol 31 (1) ◽  
pp. 3-10
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
A. M. Hahut ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Oxidative Damage ◽  
Cadmium Chloride ◽  
Glioma Cells ◽  
Low Doses ◽  
Genotoxic Effects ◽  
Cadmium Ions

Cadmium is a common transition metal that entails an extremely wide range of toxic effects in humans and animals. The cytotoxicity of cadmium ions and its compounds is due to various genotoxic effects, including both DNA damage and chromosomal aberrations. Some bone diseases, kidney and digestive system diseases are determined as pathologies that are closely associated with cadmium intoxication. In addition, cadmium is included in the list of carcinogens because of its ability to initiate the development of tumors of several forms of cancer under conditions of chronic or acute intoxication. Despite many studies of the effects of cadmium in animal models and cohorts of patients, in which cadmium effects has occurred, its molecular mechanisms of action are not fully understood. The genotoxic effects of cadmium and the induction of programmed cell death have attracted the attention of researchers in the last decade. In recent years, the results obtained for in vivo and in vitro experimental models have shown extremely high cytotoxicity of sublethal concentrations of cadmium and its compounds in various tissues. One of the most studied causes of cadmium cytotoxicity is the development of oxidative stress and associated oxidative damage to macromolecules of lipids, proteins and nucleic acids. Brain cells are most sensitive to oxidative damage and can be a critical target of cadmium cytotoxicity. Thus, oxidative damage caused by cadmium can initiate genotoxicity, programmed cell death and inhibit their viability in the human and animal brains. To test our hypothesis, cadmium cytotoxicity was assessed in vivo in U251 glioma cells through viability determinants and markers of oxidative stress and apoptosis. The result of the cell viability analysis showed the dose-dependent action of cadmium chloride in glioma cells, as well as the generation of oxidative stress (p <0.05). Calculated for 48 hours of exposure, the LD50 was 3.1 μg×ml-1. The rates of apoptotic death of glioma cells also progressively increased depending on the dose of cadmium ions. A high correlation between cadmium concentration and apoptotic response (p <0.01) was found for cells exposed to 3–4 μg×ml-1 cadmium chloride. Moreover, a significant correlation was found between oxidative stress (lipid peroxidation) and induction of apoptosis. The results indicate a strong relationship between the generation of oxidative damage by macromolecules and the initiation of programmed cell death in glial cells under conditions of low doses of cadmium chloride. The presented results show that cadmium ions can induce oxidative damage in brain cells and inhibit their viability through the induction of programmed death. Such effects of cadmium intoxication can be considered as a model of the impact of heavy metal pollution on vertebrates.

Evaluation and Avoidance of False Alarm by Controlling Rhine Water with Continuously Working Biotests

1994 ◽  
Vol 29 (3) ◽  
pp. 207-209 ◽  
Author(s):  
H. Puzicha
Keyword(s):  
Warning System ◽  
Point Sources ◽  
Trophic Levels ◽  
River Rhine ◽  
Wide Range ◽  
River Test ◽  
Continuous Working ◽  
Range Of Variation ◽  
Contaminant Load ◽  
Rhine Water

Effluents from point sources (industries, communities) and diffuse inputs introduce pollutants into the water of the river Rhine and cause a basic contaminant load. The aim is to establish a biological warning system to detect increased toxicity in addition to the already existing chemical-physical monitoring system. To cover a wide range of biocides, continuous working biotests at different trophic levels (bacteria, algae, mussels, water fleas, fishes) have been developed and proved. These are checked out for sensitivity against toxicants, reaction time, validity of data and practical handling under field conditions at the river. Test-specific appropriate methods are found to differentiate between the normal range of variation and true alarm signals.

scholarly journals Effects of Hyperglycemia on Vascular Smooth Muscle Ca2+Signaling

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Nahed El-Najjar ◽  
Rashmi P. Kulkarni ◽  
Nancy Nader ◽  
Rawad Hodeify ◽  
Khaled Machaca
Keyword(s):  
Insulin Resistance ◽  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Vascular Smooth Muscle ◽  
Complex Disease ◽  
Prolonged Exposure ◽  
In Vitro System ◽  
A7r5 Cells

Diabetes is a complex disease that is characterized with hyperglycemia, dyslipidemia, and insulin resistance. These pathologies are associated with significant cardiovascular implications that affect both the macro- and microvasculature. It is therefore important to understand the effects of various pathologies associated with diabetes on the vasculature. Here we directly test the effects of hyperglycemia on vascular smooth muscle (VSM) Ca2+signaling in an isolated in vitro system using the A7r5 rat aortic cell line as a model. We find that prolonged exposure of A7r5 cells to hyperglycemia (weeks) is associated with changes to Ca2+signaling, including most prominently an inhibition of the passive ER Ca2+leak and the sarcoplasmic reticulum Ca2+-ATPase (SERCA). To translate these findings to the in vivo condition, we used primary VSM cells from normal and diabetic subjects and find that only the inhibition of the ER Ca2+leaks replicates in cells from diabetic donors. These results show that prolonged hyperglycemia in isolation alters the Ca2+signaling machinery in VSM cells. However, these alterations are not readily translatable to the whole organism situation where alterations to the Ca2+signaling machinery are different.

scholarly journals Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons

2014 ◽  
Vol 306 (2) ◽  
pp. L170-L182 ◽  
Author(s):  
Anna A. Shvedova ◽  
Naveena Yanamala ◽  
Elena R. Kisin ◽  
Alexey V. Tkach ◽  
Ashley R. Murray ◽  
...  
Keyword(s):  
Lung Tumor ◽  
Inhalation Exposure ◽  
Geometric Feature ◽  
Width Ratio ◽  
Long Term Effects ◽  
Genotoxic Effects ◽  
Pulmonary Exposure ◽  
Pharyngeal Aspiration

The hallmark geometric feature of single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF), high length to width ratio, makes them similar to a hazardous agent, asbestos. Very limited data are available concerning long-term effects of pulmonary exposure to SWCNT or CNF. Here, we compared inflammatory, fibrogenic, and genotoxic effects of CNF, SWCNT, or asbestos in mice 1 yr after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5 h/day for 4 days, to evaluate the effect of dose rate. The aspiration studies showed that these particles can be visualized in the lung at 1 yr postexposure, whereas some translocate to lymphatics. All these particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, whereas SWCNT were the most fibrogenic of these three particles. Furthermore, SWCNT induced cytogenetic alterations seen as micronuclei formation and nuclear protrusions in vivo. Importantly, inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic, and genotoxic effects than bolus pharyngeal aspiration. Finally, SWCNT and CNF, but not asbestos exposures, increased the incidence of K-ras oncogene mutations in the lung. No increased lung tumor incidence occurred after 1 yr postexposure to SWCNT, CNF, and asbestos. Overall, our data suggest that long-term pulmonary toxicity of SWCNT, CNF, and asbestos is defined, not only by their chemical composition, but also by the specific surface area and type of exposure.

Study of Afterglow and Thermoluminescence Properties of Synthetic Opal-C Nanoparticles for In Vivo Dosimetry Applications

2013 ◽  
Vol 1530 ◽  
Author(s):  
Marlen Hernández-Ortiz ◽  
Laura S. Acosta-Torres ◽  
Rodolfo Bernal ◽  
Catalina Cruz-Vázquez ◽  
Víctor M. Castaño
Keyword(s):  
Radiation Dosimetry ◽  
Dose Range ◽  
Beta Particle ◽  
In Vivo Dosimetry ◽  
Synthetic Opal ◽  
Genotoxic Effects ◽  
Stöber Method ◽  
Particle Irradiation ◽  
The Stöber Method

ABSTRACTOpal particles, with diameter ca. 80 nm, were synthesized by the Stöber method. Samples were exposed to 100 Gy of beta particle irradiation and its thermoluminescence (TL) emission was recorded. TL response presents good reproducibility, standard deviation 1 %. The glow curve displays two TL peaks 86 and 400 °C and the afterglow (AG) phenomenon is observed immediately after irradiation (< 150°C). The synthetic opal-C exhibits a linear dependence of AG response as function of dose from 0.25 to 8 Gy. This dose range is of interest for personal and clinical dosimetry. Moreover, a previous study indicates that cytotoxic and genotoxic effects caused by opal nanoparticles, did not induce unrepairable DNA damage neither a cellular harm. Therefore, our results show synthetic opal-C is a material useful for in vivo radiation dosimetry.

Anti-Diabetic Retinopathy Potential of Noni: The beneficial effect and possible mechanism

2020 ◽  
Vol 3 (1) ◽  
pp. 01-21
Author(s):  
Faisal Ali
Keyword(s):  
Diabetic Retinopathy ◽  
Prolonged Exposure ◽  
Morinda Citrifolia ◽  
In Vivo Studies ◽  
Laboratory Research ◽  
Tropical Region ◽  
Bioactive Substances ◽  
High Blood Glucose

Noni (Morinda citrifolia L.) is being evaluated in laboratory research for its benefits as an antioxidant and immunity booster, as well as for its properties to prevent tumors and cure diabetes. The vast spread of Noni in tropical region of the globe, from America reaching to Africa and Southeast Asia, contributed in enhancing its usage and potency due to the diversity in harvest zone. Noni parts comprise fruits, seeds, leaves, and flowers are being used for individual nutritional and therapeutical values. Nevertheless, the fruit is widely characterized to contain the most valuable bioactive substances. On the other hand, diabetic retinopathy (DR) is a microvascular disorder impacting the small blood vessels in the retina, which includes microaneurysms, retinal hemorrhages, and hard exudates results from prolonged exposure to high blood glucose levels. The anti-diabetes effect of Noni extract and juice has been examined but the beneficial role of Noni and its potential mechanisms against the development of diabetic retinopathy phenotype is still ambiguous. This review, therefore, will discusses in details the pharmacological actions of M. citrifolia fruit, along with their isolated phytochemical compounds on diabetic retinopathy markers, through describing the conducted in vitro and in vivo studies as well as clinical data.

scholarly journals Evaluation of cytotoxicity and mutagenicity of the benzodiazepine flunitrazepam in vitro and in vivo

2014 ◽  
Vol 50 (2) ◽  
pp. 251-256
Author(s):  
Igor Vivian de Almeida ◽  
Giovana Domingues ◽  
Lilian Capelari Soares ◽  
Elisângela Düsman ◽  
Veronica Elisa Pimenta Vicentini
Keyword(s):  
Rattus Norvegicus ◽  
Bone Marrow Cells ◽  
Micronucleus Test ◽  
Term Treatment ◽  
Genotoxic Effects ◽  
Short Term ◽  
Short Term Treatment ◽  
Chromosomal Aberration Test

Flunitrazepam (FNZ) is a sedative benzodiazepine prescribed for the short-term treatment of insomnia. However, there are concerns regarding possible carcinogenic or genotoxic effects of this medicine. Thus, the aim of this study was to evaluate the cytotoxic, clastogenic and aneugenic effects of FNZ in hepatoma cells from Rattus norvegicus (HTC) in vitro and in bone marrow cells of Wistar rats in vivo. These effects were examined in vitro following treatment with 0.2, 1.0, 5.0 or 10 μg/mL FNZ using a micronucleus test with a cytokinesis block or in vivo using a chromosomal aberration test following treatment with 7, 15 or 30 μg/mL/kg body weight. The results showed that the benzodiazepine concentrations tested were not cytotoxic, aneugenic or clastogenic. However, considering the adverse effects of using this benzodiazepine, more studies are required.

scholarly journals Design and in vivo evaluation of a microparticulate depot formulation of buprenorphine for veterinary use

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Viktoria Schreiner ◽  
Mattea Durst ◽  
Margarete Arras ◽  
Pascal Detampel ◽  
Paulin Jirkof ◽  
...  
Keyword(s):  
Drug Release ◽  
Prolonged Exposure ◽  
Drug Formulation ◽  
Spherical Particles ◽  
Laboratory Animals ◽  
Attractive Alternative ◽  
Burst Release ◽  
In Vivo Evaluation ◽  
Duration Of Action

Abstract Buprenorphine is a frequently used analgetic agent in veterinary medicine. A major drawback, however, is the short duration of action requiring several daily administrations. We therefore designed a poly-lactic-co-glycolic acid (PLGA) based microparticulate drug formulation for sustained parenteral drug release. Particles were designed to allow for a fast onset of action and a duration of the analgesic effect of at least two days in laboratory mice. Microparticles were produced using a solvent evaporation technique. Release rate was dependent on polymer type and particle size. Spherical particles used for subsequent animal studies had a mean size of 50 µm and contained 4.5% of buprenorphine. Drug release was characterized by an initial burst release of 30% followed by complete release over seven days. In vivo pharmacokinetic experiments in female C57BL/6 J mice confirmed prolonged exposure in plasma and brain tissue and correlated with the pharmacological effect in the hot plate assay or after minor abdominal surgery. No adverse side effects with respect to food and water intake, body weight, local tolerability, or nesting behavior were observed. Our formulation is an attractive alternative to established immediate release formulations. A use for prolonged pain management in laboratory animals is proposed.

scholarly journals Changes in labial capillary density on ascent to and descent from high altitude

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2107 ◽  
Author(s):  
Edward Gilbert-Kawai ◽  
Jonny Coppel ◽  
Phillip Hennis ◽  
Michael Grocott ◽  
Can Ince ◽  
...  
Keyword(s):  
High Altitude ◽  
Correlation Coefficient ◽  
Prolonged Exposure ◽  
Haemoglobin Concentration ◽  
Capillary Density ◽  
Vessel Density ◽  
Field Of View ◽  
Rank Test ◽  
Simplified Method

Present knowledge of how the microcirculation is altered by prolonged exposure to hypoxia at high altitude is incomplete and modification of existing analytical techniques may improve our knowledge considerably. We set out to use a novel simplified method of measuring in vivo capillary density during an expedition to high altitude using a CytoCam incident dark field imaging video-microscope. The simplified method of data capture involved recording one-second images of the mucosal surface of the inner lip to reveal data about microvasculature density in ten individuals. This was done on ascent to, and descent from, high altitude. Analysis was conducted offline by two independent investigators blinded to the participant identity, testing conditions and the imaging site.  Additionally we monitored haemoglobin concentration and haematocrit data to see if we could support or refute mechanisms of altered density relating to vessel recruitment. Repeated sets of paired values were compared using Kruskall Wallis Analysis of Variance tests, whilst comparisons of values between sites was by related samples Wilcoxon Signed Rank Test. Correlation between different variables was performed using Spearman’s rank correlation coefficient, and concordance between analysing investigators using intra-class correlation coefficient. There was a significant increase in capillary density from London on ascent to high altitude; median capillaries per field of view area increased from 22.8 to 25.3 (p=0.021). There was a further increase in vessel density during the six weeks spent at altitude (25.3 to 32.5, p=0.017). Moreover, vessel density remained high on descent to Kathmandu (31.0 capillaries per field of view area), despite a significant decrease in haemoglobin concentration and haematocrit. Using a simplified technique, we have demonstrated an increase in capillary density on early and sustained exposure to hypobaric hypoxia at thigh altitude, and that this remains elevated on descent to normoxia. The technique is simple, reliable and reproducible.

scholarly journals Inhibiting autophagy targets human leukemic stem cells and hypoxic AML blasts by disrupting mitochondrial homeostasis

2021 ◽  
Vol 5 (8) ◽  
pp. 2087-2100
Author(s):  
Kaitlyn M. Dykstra ◽  
Hannah R. S. Fay ◽  
Ashish C. Massey ◽  
Neng Yang ◽  
Matthew Johnson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Mitochondrial Respiration ◽  
Prolonged Exposure ◽  
Tumor Burden ◽  
Therapeutic Interventions ◽  
Autophagic Flux ◽  
Mitochondrial Homeostasis ◽  
Nsg Mice

Abstract Leukemia stem cells (LSCs) and therapy-resistant acute myeloid leukemia (AML) blasts contribute to the reinitiation of leukemia after remission, necessitating therapeutic interventions that target these populations. Autophagy is a prosurvival process that allows for cells to adapt to a variety of stressors. Blocking autophagy pharmacologically by using mechanistically distinct inhibitors induced apoptosis and prevented colony formation in primary human AML cells. The most effective inhibitor, bafilomycin A1 (Baf A1), also prevented the in vivo maintenance of AML LSCs in NSG mice. To understand why Baf A1 exerted the most dramatic effects on LSC survival, we evaluated mitochondrial function. Baf A1 reduced mitochondrial respiration and stabilized PTEN-induced kinase-1 (PINK-1), which initiates autophagy of mitochondria (mitophagy). Interestingly, with the autophagy inhibitor chloroquine, levels of enhanced cell death and reduced mitochondrial respiration phenocopied the effects of Baf A1 only when cultured in hypoxic conditions that mimic the marrow microenvironment (1% O2). This indicates that increased efficacy of autophagy inhibitors in inducing AML cell death can be achieved by concurrently inducing mitochondrial damage and mitophagy (pharmacologically or by hypoxic induction) and blocking mitochondrial degradation. In addition, prolonged exposure of AML cells to hypoxia induced autophagic flux and reduced chemosensitivity to cytarabine (Ara-C), which was reversed by autophagy inhibition. The combination of Ara-C with Baf A1 also decreased tumor burden in vivo. These findings demonstrate that autophagy is critical for mitochondrial homeostasis and survival of AML cells in hypoxia and support the development of autophagy inhibitors as novel therapeutic agents for AML.

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