Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 635

Search results for: toxicity

605 The Relation Between Oxidative Stress, Inflammation, and Neopterin in the Paraquat-Induced Lung Toxicity

Authors: M. Toygar, I. Aydin, M. Agilli, F. N. Aydin, M. Oztosun, H. Gul, E. Macit, Y. Karslioglu, T. Topal, B. Uysal, M. Honca

Abstract:

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon g and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1 (TGF-1) levels were significantly higher than the sham group (in all, p< 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p 1/4 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1 levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Keywords: Inflammation, Oxidative Stress, paraquat, neopterin, lung toxicity

Procedia PDF Downloads 191
604 Abridging Pharmaceutical Analysis and Drug Discovery via LC-MS-TOF, NMR, in-silico Toxicity-Bioactivity Profiling for Therapeutic Purposing Zileuton Impurities: Need of Hour

Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

Abstract:

The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: Toxicity, NMR, Impurities, bio-activity, UFLC, LC-MS-TOF, Zileuton

Procedia PDF Downloads 84
603 Toxicity, Analgesic, and Anti-Pyretic Activities of Methanolic Extract from Hyoscyamus albus’ Leaves in Albinos Rats

Authors: Yahia Massinissa, Mouloud Yahia, Afaf Benhouda

Abstract:

Objective: The aim of this study was to investigate the toxicity; analgesic and anti-pyretic properties of standardized HA methanolic extract (HAMeOH) in vivo. Methods: The acute toxicity study was performed on rats while adopting the OECD-420 Guidelines (fixed dose procedure). Assessment of analgesic activity was performed in rats with two analgesic models. One was acetic acid induced writhing response and the other formalin-induced paw licking. The anti-pyretic effect was tested by Brewer’s yeast induced fever in rats. Results: For the acute toxicity test, the higher dose administration of 2000 mg/kg bw. of H.albus did not produce any toxic signs or deaths in rats. There were no significant differences (p>0.05) in the body and organ weights between control and treated groups. The (LD50) of 'H. albus' was higher than 2000 g/kg bw. In subacute toxicity study, no mortality and toxic signs were observed with the doses of 100 and 200 mg/kg bw. of extracts of for 28 consecutive days. These analgesic experimental results indicated that HAMeOH (100 mg/kg and 200 mg/kg) decreased the acetic acid-induced writhing responses and HAMeOH (100 mg/kg and 200 mg/kg) decreased the licking time in the second phase of the formalin test. Moreover, in the model of yeast-induced elevation of the body temperature HAMeOH showed dose-dependent lowering of the body temperature up to 3h at both the doses these results obtained, were comparable to that of paracetamol. Conclusion: The present findings indicate that the leaves of Hyoscyamus albus L. possess potent analgesic and antipyretic activity.

Keywords: Secondary Metabolites, Umbilicus rupestris, Hyoscyamus albus, methanolic extract, NMR with protons, pharmacobiologic activities

Procedia PDF Downloads 283
602 Persistent Toxicity of Imidacloprid to Aphis gossypii Glover and Amarasca biguttula biguttula Ishida on Okra

Authors: C. S. Patil, M. A. Pawar

Abstract:

Investigations were carried out to evaluate the persistent toxicity of imidacloprid, thiamethoxam and dimethoate to Aphis gossypii and Amrasca biguttula biguttula under laboratory condition during 2012. The experiment was conducted in a completely randomized block design with three replications in the glass house of department of Entomology M. P. K. V. Rahuri. Okra plants were raised in glass house following all recommended agronomic practices. The 21 days old plants were used for assessing the effect of insecticides on aphids and jassids. The insecticides were diluted with distilled water to make desired concentrations and used for foliar application. The insecticides included in the study were imidacloprid 17.8 SL, imidacloprid 70 WG, thiamethoxam 25 WG and dimethoate 30 EC. Untreated check was maintained by spraying with distilled water. The mortality of aphids and jassids on treated leaf were recorded at 1, 3, 5, 7, 9, 11, 13, 15, 17, 21, and 25 days after spray till zero per cent mortality observed for each treatment. Treated leaves from the glasshouse were brought to laboratory and were put in tube with moist cotton swab at the bottom of leaf and sucking apparatus was fit to the tube. Ten jassids were sucked in each tube from the plants in the field. Evaluated insecticides differed in their persistence and index of persistence toxicity against both insects of different treatments. Recommended dose of imidacloprid (25 g a.i/ha) persisted for 21 days against both aphids and jassids. However dimethoate, a conventional insecticide persisted for 11 days.

Keywords: imidacloprid, Amrasca biguttula biguttula, Aphis gossypii, persistent toxicity

Procedia PDF Downloads 49
601 Gold Nanoparticle: Synthesis, Characterization, Clinico-Pathological, Pathological and Bio-Distribution Studies in Rabbits

Authors: M. M. Bashandy, A. R. Ahmed, M. El-Gaffary, Sahar S. Abd El-Rahman

Abstract:

This study evaluated the acute toxicity and tissue distribution of intravenously administered gold nanoparticles (AuNPs) in male rabbits. Rabbits were exposed to single dose of AuNPs (300 µg/ kg). Toxic effects were assessed via general behavior, hematological parameters, serum biochemical parameters and histopathological examination of various rabbits’ organs. Tissue distribution of AuNPs was evaluated at a dose of 300 µg/ kg in male rabbit. Inductively coupled plasma–mass spectrometry (ICP-MS) was used to determine gold concentrations in tissue samples collected at predetermined time intervals. After one week, AuNPs exerted no obvious acute toxicity in rabbits. However, inflammatory reactions in lung and liver cells were induced in rabbits treated at the300 µg/ kg dose level. The highest gold levels were found in the spleen, followed by liver, lungs and kidneys. These results indicated that AuNPs could be distributed extensively to various tissues in the body, but primarily in the spleen and liver.

Keywords: Toxicity, Pathology, Hematology, gold nanoparticles, liver function, kidney function

Procedia PDF Downloads 207
600 Environmental and Toxicological Impacts of Glyphosate with Its Formulating Adjuvant

Authors: I. Székács, Á. Fejes, S. Klátyik, E. Takács, D. Patkó, J. Pomóthy, M. Mörtl, R. Horváth, E. Madarász, B. Darvas, A. Székács

Abstract:

Environmental and toxicological characteristics of formulated pesticides may substantially differ from those of their active ingredients or other components alone. This phenomenon is demonstrated in the case of the herbicide active ingredient glyphosate. Due to its extensive application, this active ingredient was found in surface and ground water samples collected in Békés County, Hungary, in the concentration range of 0.54–0.98 ng/ml. The occurrence of glyphosate appeared to be somewhat higher at areas under intensive agriculture, industrial activities and public road services, but the compound was detected at areas under organic (ecological) farming or natural grasslands, indicating environmental mobility. Increased toxicity of the formulated herbicide product Roundup, compared to that of glyphosate was observed on the indicator aquatic organism Daphnia magna Straus. Acute LC50 values of Roundup and its formulating adjuvant Polyethoxylated Tallowamine (POEA) exceeded 20 and 3.1 mg/ml, respectively, while that of glyphosate (as isopropyl salt) was found to be substantially lower (690-900 mg/ml) showing good agreement with literature data. Cytotoxicity of Roundup, POEA and glyphosate has been determined on the neuroectodermal cell line, NE-4C measured both by cell viability test and holographic microscopy. Acute toxicity (LC50) of Roundup, POEA and glyphosate on NE-4C cells was found to be 0.013±0.002%, 0.017±0.009% and 6.46±2.25%, respectively (in equivalents of diluted Roundup solution), corresponding to 0.022±0.003 and 53.1±18.5 mg/ml for POEA and glyphosate, respectively, indicating no statistical difference between Roundup and POEA and 2.5 orders of magnitude difference between these and glyphosate. The same order of cellular toxicity seen in average cell area has been indicated under quantitative cell visualization. The results indicate that toxicity of the formulated herbicide is caused by the formulating agent, but in some parameters toxicological synergy occurs between POEA and glyphosate.

Keywords: Synergy, glyphosate, polyethoxylated tallowamine, Roundup, combined aquatic and cellular toxicity

Procedia PDF Downloads 159
599 Phytochemical Screening and Toxicological Studies of Aqueous Stem Bark Extract of Boswellia papyrifera (DEL) in Rats

Authors: Y. Abdulmumin, K. I. Matazu, A. M. Wudil, A. J. Alhassan, A. A. Imam

Abstract:

Phytochemical analysis of Boswellia papryfera confirms the presence of various phytochemicals such as alkaloids, flavonoids, tannins, saponins and cardiac glycosides in its aqueous stem bark extract at different concentration, with tannins being the highest (0.611 ± 0.002 g %). Acute toxicity test (LD50, oral, rat) of the extract showed no mortality at up to 5000 mg/kg and the animals were found active and healthy. The extract was declared as practically non-toxic, this suggest the safety of the extract in traditional medicine.

Keywords: acute toxicity, aqueous extract, boswellia papryfera, phytochemicals and stem bark

Procedia PDF Downloads 208
598 Protective Effect of Cow Urine against Chlorpyrifos Induced-Genotoxicity and Neurotoxicity in Albino Rats

Authors: Shelly Sharma, Pooja Chadha

Abstract:

Humans are exposed to pesticides and insecticides either directly or indirectly. Exposure to these pesticides may lead to acute toxicity to mammals and non-target organisms. Chlorpyrifos (CPF) is a broad spectrum organophosphate pesticide widely used in various countries of the world. The aim of the present study was to assess the toxicity associated with chlorpyrifos exposure and possible mitigating effect of cow urine against genotoxic and toxic effects in rat brain induced by chlorpyrifos. For this purpose LD50 was determined and rats were orally administered with 1/8th of LD50 (19mg/kg b.wt). Brain samples were taken after 24hrs, 48hrs and 72hrs of treatment. A significant increase in the % tail DNA was observed along with the increase in MDA levels of brain tissues in chlorpyrifos treated groups as compared to control. Cow urine treated groups show decrease in DNA damage and MDA levels as compared to CPF treated group. The study indicates that cow urine has ameliorative potential against neurotoxicity and genotoxicity induced by CPF. Cow urine is considered rich in vitamin A, E and volatile fatty acids which provide antioxidant potential to it. Thus, it can be used as a genoprotective agent.

Keywords: Toxicity, Brain, Genotoxicity, comet assay, cow urine

Procedia PDF Downloads 258
597 Acute Toxicity of Atrazine Herbicide on Caspian Kutum, Rutilus frisii kutum larvae

Authors: Zahra Khoshnood, Reza Khoshnood

Abstract:

Pesticides and drugs used in agriculture and veterinary medicine may end up in aquatic environments and bio-accumulate in the food chain, thus causing serious problems for fauna and human health. For determination of the toxic effects of atrazine herbicide on Caspian kutum, Rutilus frisii kutum larvae, the 96-h LC50 of atrazine was measured for newly hatched larvae as 18.53 ppm. Toxicity of atrazine herbicide on Caspian kutum larvae was investigated using concentrations: 9.25 ppm, 4.62 ppm and 2.31 ppm for 7 days. Comparison of the length, weight and condition factor showed that no significant differences between atrazine exposed and control groups. The concentration of Na+, K+, Ca2+, Mg2+, and Cl- in whole body of larvae in control and atrazine exposure groups were measured and the results showed that concentrations of all these ions is higher in atrazine exposure group than control group. It is obvious from this study that atrazine negatively affects osmoregulation process and changes ion compositions of the body even at sub-lethal concentration and acute exposure but have no effects on growth parameters of the body.

Keywords: acute toxicity, atrazine, caspian kutum, body ions, lc50

Procedia PDF Downloads 189
596 The Effects of Root Zone Supply of Aluminium on Vegetative Growth of 15 Groundnut Cultivars Grown in Solution Culture

Authors: Mosima M. Mabitsela

Abstract:

Groundnut is preferably grown on light textured soils. Most of these light textured soils tend to be highly weathered and characterized by high soil acidity and low nutrient status. One major soil factor associated with infertility of acidic soils that can negatively depress groundnut yield is aluminium (Al) toxicity. In plants Al toxicity damages root cells, leading to inhibition of root growth as a result of the suppression of cell division, cell elongation and cell expansion in the apical meristem cells of the root. The end result is that roots become stunted and brittle, root hair development is poor, and the root apices become swollen. This study was conducted to determine the effects of aluminium (Al) toxicity on a range of groundnut varieties. Fifteen cultivars were tested in incremental aluminum (Al) supply in an ebb and flow solution culture laid out in a randomized complete block design. There were six aluminium (Al) treatments viz. 0 µM, 1 µM, 5.7 µM, 14.14 µM, 53.18 µM, and 200 µM. At 1 µM there was no inhibitory effect on the growth of groundnut. The inhibition of groundnut growth was noticeable from 5.7 µM to 200 µM, where the severe effect of aluminium (Al) stress was observed at 200 µM. The cultivars varied in their response to aluminium (Al) supply in solution culture. Groundnuts are one of the most important food crops in the world, and its supply is on a decline due to the light-textured soils that they thrive under as these soils are acidic and can easily solubilize aluminium (Al) to its toxic form. Consequently, there is a need to develop groundnut cultivars with high tolerance to soil acidity.

Keywords: Reduction, cultivars, root growth, aluminium toxicity

Procedia PDF Downloads 15
595 Impact of Two Xenobiotics in Mosquitofish: Gambusia affinis: Several Approaches

Authors: Chouahda Salima, Soltani Noureddine

Abstract:

The present study is a part of biological control against mosquitoes. It aims to assess the impact of two xenobiotics (a selective insect growth regulator: halofenozide and heavy metals: cadmium, more toxic and widespread in the region) in mosquitofish: Gambusia affinis. Several approaches were examined: Acute toxicity of cadmium and halofenozide: The acute toxicity of cadmium and halofenozide was examined in juvenile and adult males and females of G. affinis at different concentrations, cadmium causes mortality of the species studied with a relation dose-response. In laboratory conditions, the impact of cadmium was determined on two biomarkers of environmental stress: glutathione and acetylcholinesterase. The results show that the juvenile followed by adult males are more susceptible than adult females, while the halofenozide does not have any effect on the mortality of juvenile and adult males and females of G.affinis. Chronic toxicity of cadmium and halofenozide: both xenobiotics were added to the water fish raising at different doses tested in juveniles and adults males and females during two months of experience. Growth and metric indices; results show that halofenozide added to the water juveniles of G. affinis has no effect on their growth (length and weight). On the other side, the cadmium at the dose 5 µg/L shows a higher toxicity against juvenile, where he appears to reduce significantly their linear growth and weight. In females, the both xenobiotics have significant effects on metric indices, but these effects are more important on the hepatosomatic index that the gonadosomatic index and the coefficient of condition. Biomarkers; acetylcholinesterase (AChE), glutathione S-transferase (GST) and glutathione (GSH) used in assessing of environmental stress were measured in juveniles and adults males and females. The response of these biomarkers reveals an inhibition of AChE specific activity, an induction of GST activity, and decrease of GSH rates in juveniles in the end of experiment and during chronic treatment adult males and females. The effect of these biomarkers is more pronounced in females compared to males and juveniles. These different biomarkers have a similar profile for the duration of exposure.

Keywords: Biomarkers, Morphology, Pollution, acute toxicity, heavy metal, insecticide, Gambusia affinis, chronic toxicity

Procedia PDF Downloads 161
594 Determination of Acute Toxicity of Atrazine Herbicide in Caspian Kutum, Rutilus frisii kutum, Larvae

Authors: Z. Khoshnood, L. Khoshnood

Abstract:

Pesticides and drugs used in agriculture and veterinary medicine may end up in aquatic environments and bioaccumulate in the food chain, thus causing serious problems for fauna and human health. For determination of the toxic effects of atrazine herbicide on Caspian kutum, Rutilus frisii kutum larvae, the 96-h LC50 of atrazine was measured for newly hatched larvae as 18.53 ppm. Toxicity of atrazine herbicide on Caspian kutum larvae was investigated using concentrations: 9.25 ppm, 4.62 ppm and 2.31 ppm for 7 days. Comparison of the length, weight, and condition factor showed that no significant differences between atrazine exposed and control groups. The concentration of Na+, K+, Ca2+, Mg2+ and Cl- in whole body of larvae in control and atrazine exposure groups were measured and the results showed that concentrations of all these ions is higher in atrazine exposure group than control group. It is obvious from this study that atrazine negatively affects osmoregulation process and changes ion compositions of the body even at sublethal concentration and acute exposure but have no effects on growth parameters of the body.

Keywords: acute toxicity, atrazine, caspian kutum, body ions, lc50

Procedia PDF Downloads 244
593 Phytochemical Screening and Toxicological Studies of Aqueous Stem Bark Extract of Boswellia papyrifera (DEL) in Albino Rats

Authors: Y. Abdulmumin, K. I. Matazu, A. M. Wudil, A. J. Alhassan, A. A. Imam

Abstract:

Phytochemical analysis of Boswellia papryfera confirms the presence of various phytochemicals such as alkaloids, flavonoids, tannins, saponins and cardiac glycosides in its aqueous stem bark extract at different concentration, with tannins being the highest (0.611 ± 0.002 g %). Acute toxicity test (LD50,oral, rat) of the extract showed no mortality at up to 5000 mg/kg and the animals were found active and healthy. The extract was declared as practically non-toxic, this suggest the safety of the extract in traditional medicine.

Keywords: Phytochemicals, acute toxicity, aqueous extract, boswellia papryfera, stem bark extract

Procedia PDF Downloads 250
592 Protection against Sodium Arsenate Induced Fetal Toxicity in Albino Mice by Vitamin C and E

Authors: Fariha Qureshi, Mohammad Tahir

Abstract:

Epidemiological evidences indicated that arsenic contamination in drinking water increased the incidence of spontaneous abortion, stillbirth and premature babies in pregnant women. This study was designed to investigate the protective role of vitamin C&E against sodium arsenate induced fetal toxicity in albino mice. Twenty-four pregnant albino mice of BALB/c strain were randomly divided into 4 groups having 6 animals in each. Group A1 served as control and was injected with 0.1ml/kg/day distilled water I/P for 18 days. Groups A2,A3 & A4 received single I/P injection of sodium arsenate 35mg/kg on 8th gestational day, whereas groups A3 and A4 were also given Vitamin C and E by I/P injection, 9 mg/kg/day and 15 mg/kg/day respectively, starting from 8th GD and continued for the rest of the pregnancy period. The early implantation sites, fetal resorptions, weight of live fetuses and crown rump length were recorded. Gross morphological examination was carried out for malformations. Fetal kidneys were extracted for histological and micrometric analysis. Group A2 exhibited an increased incidence of abortion, fetal resorptions, significant decrease in number of litter and fetal weight; the difference of means was statistically significant among the groups (p<0.000). In group A2 fetal kidneys presented glomerulonephritis with acute tubular necrotic changes and interstitial fibrosis. Groups A3&A4 showed statistically significant improvement in these parameters. The results revealed the antioxidant potential of Vitamin C and E in protecting against arsenic induced fetal toxicity in mice.

Keywords: fetal toxicity, fetal resorptions, interstitial fibrosis, tocopherol

Procedia PDF Downloads 148
591 Evaluation of Developmental Toxicity and Teratogenicity of Perfluoroalkyl Compounds Using FETAX

Authors: Hyun-Shik Lee, Hyun-Kyung Lee, Jehyung Oh, Young Eun Jeong

Abstract:

Perfluoroalkyl compounds (PFCs) are environmental toxicants that persistently accumulate in the human blood. Their widespread detection and accumulation in the environment raise concerns about whether these chemicals might be developmental toxicants and teratogens in the ecosystem. We evaluated and compared the toxicity of PFCs of containing various numbers of carbon atoms (C8-11 carbons) on vertebrate embryogenesis. We assessed the developmental toxicity and teratogenicity of various PFCs. The toxic effects on Xenopus embryos were evaluated using different methods. We measured teratogenic indices (TIs) and investigated the mechanisms underlying developmental toxicity and teratogenicity by measuring the expression of organ-specific biomarkers such as xPTB (liver), Nkx2.5 (heart), and Cyl18 (intestine). All PFCs that we tested were found to be developmental toxicants and teratogens. Their toxic effects were strengthened with increasing length of the fluorinated carbon chain. Furthermore, we produced evidence showing that perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFuDA) are more potent developmental toxicants and teratogens in an animal model compared to the other PFCs we evaluated [perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA)]. In particular, severe defects resulting from PFDA and PFuDA exposure were observed in the liver and heart, respectively, using the whole mount in situ hybridization, real-time PCR, pathologic analysis of the heart, and dissection of the liver. Our studies suggest that most PFCs are developmental toxicants and teratogens, however, compounds that have higher numbers of carbons (i.e., PFDA and PFuDA) exert more potent effects.

Keywords: Development, PFC, xenopus, fetax

Procedia PDF Downloads 197
590 Toxicity of PPCPs on Adapted Sludge Community

Authors: G. Amariei, K. Boltes, R. Rosal, P. Leton

Abstract:

Wastewater treatment plants (WWTPs) are supposed to hold an important place in the reduction of emerging contaminants, but provide an environment that has potential for the development and/or spread of adaptation, as bacteria are continuously mixed with contaminants at sub-inhibitory concentrations. Reviewing the literature, there are little data available regarding the use of adapted bacteria forming activated sludge community for toxicity assessment, and only individual validations have been performed. Therefore, the aim of this work was to study the toxicity of Triclosan (TCS) and Ibuprofen (IBU), individually and in binary combination, on adapted activated sludge (AS). For this purpose a battery of biomarkers were assessed, involving oxidative stress and cytotoxicity responses: glutation-S-transferase (GST), catalase (CAT) and viable cells with FDA. In addition, we compared the toxic effects on adapted bacteria with unadapted bacteria, from a previous research. Adapted AS comes from three continuous-flow AS laboratory systems; two systems received IBU and TCS, individually; while the other received the binary combination, for 14 days. After adaptation, each bacterial culture condition was exposure to IBU, TCS and the combination, at 12 h. The concentration of IBU and TCS ranged 0.5-4mg/L and 0.012-0.1 mg/L, respectively. Batch toxicity experiments were performed using Oxygraph system (Hansatech), for determining the activity of CAT enzyme based on the quantification of oxygen production rate. Fluorimetric technique was applied as well, using a Fluoroskan Ascent Fl (Thermo) for determining the activity of GST enzyme, using monochlorobimane-GSH as substrate, and to the estimation of viable cell of the sludge, by fluorescence staining using Fluorescein Diacetate (FDA). For IBU adapted sludge, CAT activity it was increased at low concentration of IBU, TCS and mixture. However, increasing the concentration the behavior was different: while IBU tends to stabilize the CAT activity, TCS and the mixture decreased this one. GST activity was significantly increased by TCS and mixture. For IBU, no variations it was observed. For TCS adapted sludge, no significant variations on CAT activity it was observed. GST activity it was significant decreased for all contaminants. For mixture adapted sludge the behaviour of CAT activity it was similar to IBU adapted sludge. GST activity it was decreased at all concentration of IBU. While the presence of TCS and mixture, respectively, increased the GST activity. These findings were consistent with the viability cells evaluation, which clearly showed a variation of sludge viability. Our results suggest that, compared with unadapted bacteria, the adapted bacteria conditions plays a relevant role in the toxicity behaviour towards activated sludge communities.

Keywords: Toxicity, mixture, adapted sludge community, PPCPs

Procedia PDF Downloads 291
589 Pharmacogenetics of Uridine Diphosphate Glucuronosyltransferase (UGT1A9) Genetic Polymorphism on Sodium Valproate Pharmacokinetics in Epilepsy

Authors: Murali Munisamy, Gauthaman Karunakaran, Mubarak Al-Gahtany, Vivekanandhan Subbiah, M. Manjari Tripati

Abstract:

Background: Sodium valproate is a widely prescribed broad-spectrum anti-epileptic drug. It shows high inter-individual variability in pharmacokinetics and pharmacodynamics and has a narrow therapeutic range. We evaluated the effects of polymorphic uridine diphosphate glucuronosyltransferase (UGT1A9) metabolizing enzyme on the pharmacokinetics of sodium valproate in the patients with epilepsy who showed toxicity to therapy. Methods: Genotype analysis of the patients was made with polymerase chain–restriction fragment length polymorphism (RFLP) with sequencing. Plasma drug concentrations were measured with reversed phase high-performance liquid chromatography (HPLC) and concentration–time data were analyzed by using a non-compartmental approach. Results: The results of this study suggested a significant genotypic as well as allelic association with valproic acid toxicity for UGT1A9 polymorphic enzymes. The elimination half-life (t 1/2=40.2 h) of valproic acid was longer and the clearance rate (CL=937 ml/h) was lower in the poor metabolizers group of UGT1A9 polymorphism who showed toxicity than in the intermediate metabolizers group (t1/2=35.5 h, CL=1042 ml/h) or the extensive metabolizers group (t1/2=26. h, CL=1,302 ml/h). Conclusion: Our findings suggest that the UGT1A9 genetic polymorphism plays a significant role in the steady state concentration of sodium valproate, and it thereby has an impact on the toxicity of the sodium valproate used in the patients with epilepsy.

Keywords: Pharmacogenetics, Polymorphism, UGT1A9, sodium valporate

Procedia PDF Downloads 297
588 Studies on Effect of Nano Size and Surface Coating on Enhancement of Bioavailability and Toxicity of Berberine Chloride; A p-gp Substrate

Authors: Sanjay Singh, Parameswara Rao Vuddanda

Abstract:

The aim of the present study is study the factual benefit of nano size and surface coating of p-gp efflux inhibitor on enhancement of bioavailability of Berberine chloride (BBR); a p-gp substrate. In addition, 28 days sub acute oral toxicity study was also conducted to assess the toxicity of the formulation on chronic administration. BBR loaded polymeric nanoparticles (BBR-NP) were prepared by nanoprecipitation method. BBR NP were surface coated (BBR-SCNP) with the 1 % w/v of vitamin E TPGS. For bioavailability study, total five groups (n=6) of rat were treated as follows first; pure BBR, second; physical mixture of BBR, carrier and vitamin E TPGS, third; BBR-NP, fourth; BBR-SCNP and fifth; BBR and verapamil (widely used p-gp inhibitor). Blood was withdrawn at pre-set timing points in 24 hrs study and drug was quantified by HPLC method. In oral chronic toxicity study, total four groups (n=6) were treated as follows first (control); water, second; pure BBR, third; BBR surface coated nanoparticles and fourth; placebo BBR surface coated nanoparticles. Biochemical levels of liver (AST, ALP and ALT) and kidney (serum urea and creatinine) along with their histopathological studies were also examined (0-28 days). The AUC of BBR-SCNP was significantly 3.5 folds higher compared to all other groups. The AUC of BBR-NP was 3.23 and 1.52 folds higher compared to BBR solution and BBR with verapamil group, respectively. The physical mixture treated group showed slightly higher AUC than BBR solution treated group but significantly low compared to other groups. It indicates that encapsulation of BBR in nanosize form can circumvent P-gp efflux effect. BBR-NP showed pharmacokinetic parameters (Cmax and AUC) which are near to BBR-SCNP. However, the difference in values of T1/2 and clearance indicate that surface coating with vitamin E TPGS not only avoids the P-gp efflux at its absorption site (intestine) but also at organs which are responsible for metabolism and excretion (kidney and liver). It may be the reason for observed decrease in clearance of BBR-SCNP. No toxicity signs were observed either in biochemical or histopathological examination of liver and kidney during toxicity studies. The results indicate that administration of BBR in surface coated nanoformulation would be beneficial for enhancement of its bioavailability and longer retention in systemic circulation. Further, sub acute oral dose toxicity studies for 28 days such as evaluation of intestine, liver and kidney histopathology and biochemical estimations indicated that BBR-SCNP developed were safe for long use.

Keywords: Bioavailability, berberine nanoparticles, p-gp efflux inhibitor, nanoprecipitation method

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587 The Toxic Effects of Kynurenine Metabolites on SH-SY5Y Neuroblastoma Cells

Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora

Abstract:

Introduction /Aim: The kynurenine pathway is thought to play an important role in the pathophysiology of numerous neurodegenerative diseases including depression, Alzheimer’s disease, and Parkinson’s disease. Numerous neuroactive compounds, including the neurotoxic 3-hydroxyanthranilic acid, 3-hydroxykynurenine and quinolinic acid and the neuroprotective kynurenic acid and picolinic acid, are produced through the metabolism of kynurenine and are thought to be the causative agents responsible for neurodegeneration. The toxicity of 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid has been widely evaluated and demonstrated in primary cell cultures but to date only 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been shown to cause toxicity in immortal tumour cells. The aim of this study was to evaluate the toxicity of kynurenine metabolites, both individually and in combination, on SH-SY5Y neuroblastoma cells after 24 and 72 h exposure in order to explore a cost-effective model to study their neurotoxic effects and potential protective agents. Methods: SH-SY5Y neuroblastoma cells were exposed to various concentrations of the neuroactive kynurenine metabolites, both individually and in combination, for 24 and 72 h, and viability was subsequently evaluated using the Resazurin (Alamar blue) proliferation assay. Furthermore, the effects of these compounds, alone and in combination, on specific death pathways including apoptosis, necrosis and free radical production was evaluated using various assays. Results: Consistent with literature, toxicity was shown with short-term 24-hour treatments at 1000 μM concentrations for both 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Combinations of kynurenine metabolites showed modest toxicity towards SH-SY5Y neuroblastoma cells in a concentration-dependent manner. Specific cell death pathways, including apoptosis, necrosis and free radical production were shown to be increased after both 24 and 72 h exposure of SH-SY5Y neuroblastoma cells to 3-hydroxykynurenine and 3-hydroxyanthranilic acid and various combinations of neurotoxic kynurenine metabolites. Conclusion: It is well documented that neurotoxic kynurenine metabolites show toxicity towards primary human neurons in the nanomolar to low micromolar concentration range. Results show that the concentrations required to show significant cell death are in the range of 1000 µM for 3-hydroxykynurenine and 3-hydroxyanthranilic acid and toxicity of quinolinic acid towards SH-SY5Y was unable to be shown. This differs significantly from toxicities observed in primary human neurons. Combinations of the neurotoxic metabolites were shown to have modest toxicity towards these cells with increased toxicity and activation of cell death pathways observed after 72 h exposure. This study suggests that the 24 h model is unsuitable for use in neurotoxicity studies, however, the 72 h model better represents the observations of the studies using primary human neurons and may provide some benefit in providing a cost-effective model to assess possible protective agents against kynurenine metabolite toxicities.

Keywords: neurotoxicity, kynurenine metabolites, quinolinic acid, SH-SY5Y neuroblastoma

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586 A Computational Study Concerning the Biological Effects of the Most Commonly Used Phthalates

Authors: Adriana Isvoran, Dana Craciun, Daniela Dascalu

Abstract:

Phthalates are a class of plastic additives that are used to enhance the physical properties of plastics and as solvents in paintings and some of them proved to be of particular concern for the human health. There are insufficient data concerning the health risks of phthalates and further research on evaluating their effects in humans is needed. As humans are not volunteers for such experiments, computational analysis may be used to predict the biological effects of phthalates in humans. Within this study we have used some computational approaches (SwissADME, admetSAR, FAFDrugs) for predicting the absorption, distribution, metabolization, excretion and toxicity (ADME-Tox) profiles and pharmacokinetics for the most common used phthalates. These computational tools are based on quantitative structure-activity relationship modeling approach. The predictions are further compared to the known effects of each considered phthalate in humans and correlations between computational results and experimental data are discussed. Our data revealed that phthalates are a class of compounds reflecting high toxicity both when ingested and when inhaled, but by inhalation their toxicity is even greater. The predicted harmful effects of phthalates are: toxicity and irritations of the respiratory and gastrointestinal tracts, dyspnea, skin and eye irritations and disruption of the functions of liver and of the reproductive system. Many of investigated phthalates are predicted to be able to inhibit some of the cytochromes involved in the metabolism of numerous drugs and consequently to affect the efficiency of administrated treatments for many diseases and to intensify the adverse drugs reactions. The obtained predictions are in good agreement with clinical data concerning the observed effects of some phthalates in cases of acute exposures. Our study emphasizes the possible health effects of numerous phthalates and underlines the applicability of computational methods for predicting the biological effects of xenobiotics.

Keywords: Pharmacokinetics, Biological Effects, phthalates, ADME-Tox

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585 Impact of a Biopesticide Formulated an Entomopathogenic Fungus Metarhizium Anisopliae et Abstracts of Two Different Plants Sage (Salvia officinalis) and American Paper (Schinus molle) on Aphis Fabae (Homoptera - Aphididae)

Authors: Hicham Abidallah

Abstract:

In this work we realized a formulation of an entomopathogenic fungus Metarhizium anisopliae with a dose of 1,7 x 105 spores/ml, and aqueous abstracts of two different plants sage (Salvia officinalis) and American paper (Schinus molle) with they’re full dose and half dose, on a black bean aphid populations (Aphis fabae) on a bean crop planted in pots at semi-controlled conditions. Five formulations were achieved (Met, Fd, F1/2d, Sd et S1/2d) and tested on six blocks each one contained six pots. This study revealed that four (04) formulations exercised an influence over black bean aphid (Met, Fd, F1/2d, Sd), of which Metarhizium marked the most elevated and aggressive toxicity with an efficiency of 99,24%, however, sage formulation with the half dose (S1/2d ) marked a weak toxicity with an efficiency of 18%. Test of Metarhizium anisopliae on bees didn’t show toxicity, and no mortality has been marked, and no trace of green Muscardine observed.

Keywords: Salvia officinalis, Metarhizium anisopliae, Schinus molle, Aphis fabae, efficiency degree

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584 Nanoparticles on Biological Biomarquers Models: Paramecium Tetraurelia and Helix aspersa

Authors: M. Djekoun, M. R. Djebar, H. Djebar, L. Khene, M. Boucenna, M. N. Khebbeb

Abstract:

Currently in toxicology, use of alternative models permits to understand the mechanisms of toxicity at different levels of cells. Objectives of our research concern the determination of NPs ZnO, TiO2, AlO2, and FeO2 effect on ciliate protist freshwater Paramecium sp and Helix aspersa. The result obtained show that NPs increased antioxidative enzyme activity like catalase, glutathione –S-transferase and level GSH. Also, cells treated with high concentrations of NPs showed a high level of MDA. In conclusion, observations from growth and enzymatic parameters suggest on one hand that treatment with NPs provokes an oxidative stress and on the other that snale and paramecium are excellent alternatives models for ecotoxicological studies.

Keywords: Toxicity, catalase, MDA, GST, NPS, GSH, snale and paramecium

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583 Subacute Toxicity Study of Total Alkaloids of Seeds of Peganum harmala in Female Rat

Authors: Bouzidi Abdelouahab, Ghadjati Nadhra, Bettihi Sara, Mahdeb Nadia, Daamouche Z. El Youm

Abstract:

The effects of subacute administration of total alkaloids of seeds Peganum harmala were studied in female Albino-Wistar rats. After intraperitoneal administration of dose 50 mg/kg for 10 days and 40 mg/kg for 7 days of total alkaloids to the seeds of Peganum harmala (animal treatment lasted 17 days), there were remarkable changes in general appearance and deaths occurred in experimental group. After 17 days a significant reduction was observed in the surviving animals treated with total alkaloid seeds.The Red Blood Cells (RBC), Hematocrit (HCT), Hemoglobin (HGB) and White blood cells (WBCs), show significant reduction in the treated groups. There were no statistical differences in Glutamic-Oxaloacetic Transaminase (GOT), Glutamic-pyruvic Transaminase (GPT) and Alkaline Phosphatase (ALP), total protein, glucose and creatinine observed between groups. However the urea was significantly higher in the treated female rats than the control group. Histological examination of liver showed no histopathological changes. Alkaloids of Peganum harmala showed significant toxicity in female rats.

Keywords: Toxicity, Liver, Kidney, Alkaloids, rat, Peganum harmala

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582 Neuroprotective Effect of Germinated Dolichos lablab on 6-Hydroxy Dopamine (6-OHDA) Induced Toxicity in SH-SY5Y Neuroblastoma Cell

Authors: Lalita Subedi, Sun Yeou Kim, Taek Hwan Lee, Moon Ho Do, Young Un Park

Abstract:

Natural and artificial toxic substances namely neurotoxins induce the bitter effect in the nervous system termed as neurotoxicity. It can modulate the normal functioning of the nervous system either hyperactivate it or damage homeostasis of neuronal system. Neurotoxins induced toxicity ultimately kills the neuron. The present study investigated the neuroprotective effects of germinated Dolichos lablab on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using SH-SY5Y neuroblastoma cells. Germination is a process of plant growth from a seed. Sprouting of a seedling from a seed induced many molecular changes in the seed in order to prepare it for further growth. Because of these molecular and chemical changes, the neuroprotective effect of Dolichos lablab is higher in the germinated form than in the normal condition. SH-SY5Y cells were treated with Dolichos lablab extract (50, 100 g/ml) followed by 6-OHDA (25M) induced toxicity. Cell Viability was measured to check the cell survival against 6-OHDA induced toxicity using MTT assay. Dolichos lablab showed a neuroprotective effect against 6-OHDA induced neuronal cell death in neuroblastoma cell at a higher concentration of 100g/ml however the effect is much better even at the lower concentration after germination 50g/ml. Cell survival was increased dramatically after 15 h of germination and increased with time of germination in concentration dependent manner. Trigonelline as a representative compound was validated in germinated Dolichos lablab by HPLC analysis that might enhance the neuroprotective effect of Dolichos lablab. This result suggests that Dolichos lablab possess neuroprotective effect in neuroblastoma cells against 6-OHDA however its activity was more potent in the germinated form.

Keywords: Neuroprotection, Germination, dolichos lablab, trigonelline

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581 Functionalization of Carboxylated Single-Walled Carbon Nanotubes with 2-En 4-Hydroxy Cyclo 1-Octanon and Toxicity Investigation

Authors: D. ChobfroushKhoei, S. K. Heidari, Sh. Dariadel

Abstract:

Carbon nanotubes were used in medical sciences especially in drug delivery system and cancer therapy. In this study, we functionalized carboxylated single-wall carbon nanotubes (SWNT-COOH) with 2-en 4-hydroxy cyclo 1-octanon. Synthesized sample was characterized by FT-IR, Raman spectroscopy, SEM, TGA and cellular investigations. The results showed well formation of SWNT-Ester. Cell viability assay results and microscopic observations demonstrated that cancerous cells were killed in the sample. The synthesized sample can be used as a toxic material for cancer therapy.

Keywords: functionalization, MWNT-COOH, phenylisocyanate, phenylisothiocyanate, toxicity investigation

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580 Repeated Dose 28-Day Oral Toxicity Study Offungicides: Propinèbe, Propiconazole, And Their Mixture in Wistar Rats

Authors: Aiche Mohamed Amine, Mallem Leila, Yahia El Khansa, Boulakoud Mohamed Salah

Abstract:

Until recently, toxicological studies focused on the effects of individual chemicals. However, humans and wildlife are exposed to a complex milieu of chemicals from different sources including food and water, personal care products and the environment. The aim of this study is to detect the toxicity of two fungicides and their mixtures in the fertility and oxidative damge induced in the rat. The male of rats (28) were used, they were divided in four groups (7 rats of each group) and one group was used as control. Rats were dosed orally with Propiconazole 60mg/Kg/day, Propinebe 100mg/Kg/day and their mixture 30mg Propiconazole/kg/day + 50mg Propineb/kg/day for 4 weeks. Animals were observed for clinical toxicity. At the end of treatment period, animals of all groups were scarified, blood was collected for hematological and biochemical’s analysis and desired organs were removed and weighted. The results indicated that the fungicide and their mixture were toxic in the treated animals. The semen study showed a decrease in the count and mobility of spermatozoa in all treated group, it was also a decrease in the weight of the testis and epidydimis in the treated group as compared with control. Reduced glutathione (GSH), Glutathione peroxidase (GPx) level was decreased in all treated groups.

Keywords: Fungicides, Oxidative Stress, Fertility, mixtures

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579 The Protective Effect of Grape Seed Oil with Use of Ciprofloxacin Induced Germ Cell Toxicity in Male Albino Mice

Authors: Galawezh Obaid Othman

Abstract:

The present investigation was undertaken to evaluate the germ cell toxicity induced by ciprofloxacin antibiotic and the Protective effect of grape seed oil, Ciproflaxin uses include treatment of genitor-urinary and some reproductive tract bacterial infections. One of the most attractive approaches to disease prevention involves the use of natural antioxidants to protect tissue against toxic injury, the possible protective effect of grape seed oil, against ciprofloxacin induced reproductive toxicity on mouse .the animals were randomly divided into four groups consisting of five mice. Group (1) was orally given distilled water (solvent of the used drugs) and kept as a control. Group (2) was administered 6ml/kg. b.w of grape seed oil orally 15 days .Group (3) was administered 206mg/kg. b.w of ciprofloxacin orally for 15 days.. Last group was treated orally with Grape seed oil (6mg/kg b.w. /day) prior to an orally administered ciprofloxacin (CPX) at a dose of 206 mg⁄kg. b.w. by three hours for fifteen days. Ciproflaxin have ability to induce various types of sperm abnormalities such as (Sperm without head, sperm without tail, defective head spearm,swollen head sperm ), The results explored that Grape seed oil possesses statistically significant (p<0.05) protective potential against Ciproflaxin by decreasing sperm abnormalities frequency in mouse.

Keywords: ciprofloxacin, antimutagen, grape seed oil, germ cell

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578 Oral Toxicity of Low Doses of Fungicides, Propinebe, Propiconazole and Their Mixtures in the Male Rat

Authors: Aiche Mohamed Amine, Mallem Leila, Boulakoud Mohamed Salah

Abstract:

A number of chemical compounds are being used to protect agricultural crops from diseases. Residues of these chemicals lead to environmental pollution and pose some threat to non target organisms, human and animal. The aim of this study is to detect the toxicity of these fungicides and their mixtures in the fertility and biochemical’s parameters in the rat. The male of rats (28) were used, they were divided in four groups (7 rats of each group) and one group was used as control. Rats were dosed orally with propiconazole (60 mg/kg body weight/day), propinebe (100 mg/Kg body weight/day) and their mixture (50:50) for 4 weeks. Animals were observed for clinical toxicity. At the end of treatment period, animals of all groups were scarified and samples of different organs were fixed in the formol 10% for histopathological study, and blood was collected for hematological and biochemical’s analysis. The results indicated that the fungicide and their mixture of fungicides were toxic in the treated animals. The semen study showed a decrease in the count, mobility and speed of spermatozoa in all treated group especially those dosed with the mixture and Propiconazole, it was also a decrease in the weight of the testis and epidydimis in the treated group as compared with control. Remarquable histological changes were observed in the testis and epidydimis and liver in the group treated with mixture.

Keywords: Fungicides, Fertility, Hematological, mixture, biochemical's parameters

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577 Standards of Toxicity and Food Security in Brazil

Authors: Ana Luiza Da Gama E Souza

Abstract:

This article aims to discuss the problem of food insecurity in Brazil in what it refers to contamination of food by chemical substances such as herbicides, pesticides, and other contaminants. The issue will be faced by analyzing, on the one hand, the standards that guide the food system in the world and, on the other hand, human rights indicators whose purpose is to provide an effective monitoring of the State's obligations to guarantee food security, analyzing the implications of the former for the success of the latter. The methodology adopted in this article was bibliographic-documentary and consists of three moments of analysis. The first moment consists in the analysis of the reports of the Commission on Human Rights of the Organization of American States to identify the set of progress indicators developed by the Commission. This analysis will involve the new methodology used to evaluate the efficiency in monitoring food security in Brazil the case of using pesticides in the production of food at levels of toxicity not admitted by the inspection bodies. The second moment consists in evaluating the mechanism for monitoring food security in Brazil, which was initially established by the National Food Security Plan (PLANSAN) for 2012-2015 and improved by the II National Food Security Plan for 2016-2019. Those mechanisms were prepared by the Chamber (CAISAN), and have the function to compare the monitoring proposals with the results presented by CAISAN on the Indicators and Results Report of the National Plan for Food and Nutrition Security 2012-2015. The third moment was intended to understand, analyze and evaluate the standardization process of the agri-food system, especially regarding the level of toxicity standards, that is related to food safety monitoring as a guarantee of pesticide-free food. The results show the dependence between private standards of toxicity and the indicators of food safety that leads to inefficiency on monitoring that mechanism in Brazil.

Keywords: Food Security, Human Rights, Standards, indicators

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576 Effect of Pristine Graphene on Developmental Toxicity in Zebrafish (Danio rerio) Embryos: Cardiovascular Defects, Apoptosis, and Globin Expression Analysis

Authors: Manjunatha Bangeppagari, Lee Sang Joon

Abstract:

Recently, graphene-related nanomaterials are receiving fast-increasing attention with augmented applications in various fields. Especially, graphene-related materials have been widely applied to the biomedical field in the past years. In the present study, we evaluated the adverse effects of pristine graphene (pG) in zebrafish (Danio rerio) embryos in various aspects, such as mortality rate, heart rate, hatching rate, cardiotoxicity, cardiovascular defect, cardiac looping, apoptosis, and globin expression. For various trace concentrations of pG (1, 5, 10, 15, 20, 25, 30, 35, 40, 45, and 50 μg/L), early life-stage parameters were observed at 24, 48, 72, and 96 hpf. As a result, pG induces significant developmental defects including yolk sac edema, pericardial edema, embryonic mortality, delayed hatching, heartbeat, several morphological defects, pericardial toxicity, and bradycardia. Moreover, the exposure to pG was found to be a potential risk factor to the cardiovascular system of zebrafish embryos. However, further study on their properties which vary according to production methods and surface functionalization is essentially required. In addition, the possible risks of pG flakes to aquatic animals, and public health should be evaluated before releasing them to the surrounding environment.

Keywords: apoptosis, cardiovascular toxicity, globin expression, pristine graphene, zebrafish embryos

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