Search results for: radiotherapy toxicity

Authors: Zahra Khoshnood, Reza Khoshnood

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

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Authors: Mosima M. Mabitsela

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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: aluminium toxicity, cultivars, reduction, root growth

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Authors: Chouahda Salima, Soltani Noureddine

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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: gambusia affinis, insecticide, heavy metal, morphology, biomarkers, chronic toxicity, acute toxicity, pollution

Procedia PDF Downloads 287

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: atrazine, Caspian Kutum, acute toxicity, body ions, LC50

Procedia PDF Downloads 334

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

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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, stem bark extract

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Authors: Fariha Qureshi, Mohammad Tahir

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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

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

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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: PFC, xenopus, fetax, development

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

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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: adapted sludge community, mixture, PPCPs, toxicity

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

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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: UGT1A9, sodium valporate, pharmacogenetics, polymorphism

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Authors: Akbar Esmaeili, Fateme Dadashi

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Bismuth can increase radiation and reduce the dose of radiotherapy. On the other hand, hyaluronic acid plays a role in healing damaged cells, and melittin has been used to destroy cancer cells. This research aims to destroy eye cancer cells and accelerate the recovery of damaged healthy cells during treatment. In this research, we used this nanoparticle, the sol-gel method. According to the optimization process that was carried out, we obtained the optimal value of the desired variables for the manufacture of nanoparticles. The advantage of doing this is reducing the amount of medicine used, as a result of reducing the number of side effects during the treatment and using melittin as an anti-eye cancer drug and the presence of hyaluronic acid to accelerate the recovery of cells, as well as coating the bismuth nanoparticle with chitosan to increase the half-life of the nanoparticle and prevent its adhesion.

Keywords: synthesis, nanoparticles, coated, cancer

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Authors: Auwal Abubakar, Shazril Imran Shaukat, Noor Khairiah A. Karim, Mohammed Zakir Kassim, Gokula Kumar Appalanaido, Hafiz Mohd Zin

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Background: Voluntary deep inspiration breath-hold radiotherapy (vDIBH-RT) is an effective cardiac dose reduction technique during left breast radiotherapy. This study aimed to assess the accuracy of the implementation of the vDIBH technique among left breast cancer patients without the use of a special device such as a surface-guided imaging system. Methods: The vDIBH-RT technique was implemented among thirteen (13) left breast cancer patients at the Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia. Breath-hold monitoring was performed based on breath-hold skin marks and laser light congruence observed on zoomed CCTV images from the control console during each delivery. The initial setup was verified using cone beam computed tomography (CBCT) during breath-hold. Each field was delivered using multiple beam segments to allow a delivery time of 20 seconds, which can be tolerated by patients in breath-hold. The data were analysed using an in-house developed MATLAB algorithm. PTV margin was computed based on van Herk's margin recipe. Results: The setup error analysed from CBCT shows that the population systematic error in lateral (x), longitudinal (y), and vertical (z) axes was 2.28 mm, 3.35 mm, and 3.10 mm, respectively. Based on the CBCT image guidance, the Planning target volume (PTV) margin that would be required for vDIBH-RT using CCTV/Laser monitoring technique is 7.77 mm, 10.85 mm, and 10.93 mm in x, y, and z axes, respectively. Conclusion: It is feasible to safely implement vDIBH-RT among left breast cancer patients without special equipment. The breath-hold monitoring technique is cost-effective, radiation-free, easy to implement, and allows real-time breath-hold monitoring.

Keywords: vDIBH, cone beam computed tomography, radiotherapy, left breast cancer

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Authors: Sanjay Singh, Parameswara Rao Vuddanda

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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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Authors: Levylee Bautista, Dawn Grace Santos, Aishwarya Veluchamy, Jesusa Santos, Ghafoor Haque, Jr. I, Rodolfo Rafael

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Sesbania grandiflora is widely used in traditional medicine to treat a wide range of ailments. Assessment of its toxic properties is hence crucial when considering public health protection because exposure to plant extracts may pose adverse effects on consumers. This study aimed to investigate the acute intraperitoneal toxicity of S. grandiflora flower methanolic extract (SGFME) in Swiss albino mice. Four different concentrations (11.25, 22.5, 40, and 90 mg/kg) of SGFME were administered intraperitoneally and immediate behavioral and clinical signs were observed. All concentrations of SGFME-treated mice exhibited gasping and faster respiratory rate, writhing, reddening and fanning of the ears, paralysis of the hind leg, and mortality. Such reactions may be attributed to the histamine and saponin content of S. grandiflora. Results of this study suggests that intraperitoneal administration of SGFME produced significant adverse effect in mice, therefore, caution should be exercised in using it as herbal remedy since there is little control over its quality.

Keywords: acute toxicity test, histamine, medicinal plants, Sesbania grandiflora

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Authors: H. Yousefnia, R. Enayati, M. Hosntalab, S. Zolghadri, A. Bahrami-Samani

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Bone metastases occur in many cases at an early stage of the tumour disease, however their symptoms are recognized rather late. The aim of this study was the preparation of 153Sm-(4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl) 1,4,7,10-tetraazacyclododec-1-yl) acetic acid (BPAMD) for bone pain palliation therapy. 153Sm was produced at Tehran research reactor via 152Sm(n,γ)153Sm reaction. 200 µl of 1mg/ml BPAMD solution was added to the vial containing 1 mCi 153Sm and the mixture was heated up to 90 0C for 1 h. The radiochemical purity of the complex was measured by ITLC method. The final solution with radiochemical purity of more than 95% was injected to BALB mice and bio distribution was determined up to 48 h. SPECT images were acquired after 2 and 24 h post injection. While high bone uptake was confirmed by both the bio distribution studies and SPECT imaging, accumulation in other organs was approximately negligible. The results show that 153Sm-BPAMD can be used as an excellent tracer for bone pain palliation therapy.

Keywords: bone metastases, BPAMD, 153Sm, radiotherapy

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Authors: Sujan Mahamud

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Purpose: A major challenge in radiotherapy treatment is to deliver precise dose of radiation to the tumor with minimum dose to the healthy normal tissues. Recently, gel dosimetry has emerged as a powerful tool to measure three-dimensional (3D) dose distribution for complex delivery verification and quality assurance. These dosimeters act both as a phantom and detector, thus confirming the versatility of dosimetry technique. The aim of the study is to know the application of Gel Dosimeters in Radiotherapy and find out the comparison with 1D and 2D dimensional dosimeters. Methods and Materials: The study is carried out from Gel Dosimeter literatures. Secondary data and images have been collected from different sources such as different guidelines, books, and internet, etc. Result: Analyzing, verifying, and comparing data from treatment planning system (TPS) is determined that gel dosimeter is a very excellent powerful tool to measure three-dimensional (3D) dose distribution. The TPS calculated data were in very good agreement with the dose distribution measured by the ferrous gel. The overall uncertainty in the ferrous-gel dose determination was considerably reduced using an optimized MRI acquisition protocol and a new MRI scanner. The method developed for comparing measuring gel data with calculated treatment plans, the gel dosimetry method, was proven to be a useful for radiation treatment planning verification. In 1D and 2D Film, the depth dose and lateral for RMSD are 1.8% and 2%, and max (Di-Dj) are 2.5% and 8%. Other side 2D+ ( 3D) Film Gel and Plan Gel for RMSDstruct and RMSDstoch are 2.3% & 3.6% and 1% & 1% and system deviation are -0.6% and 2.5%. The study is investigated that the result fined 2D+ (3D) Film Dosimeter is better than the 1D and 2D Dosimeter. Discussion: Gel Dosimeters is quality control and quality assurance tool which will used the future clinical application.

Keywords: gel dosimeters, phantom, rmsd, QC, detector

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Authors: Norsyamimi Hassim, Masturah Markom

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Supercritical fluid extraction (SFE) has been known as a sustainable and safe extraction technique for plant extraction due to the minimal usage of organic solvent. In this study, a scale-up process for the selected herbal plant (Phyllanthus niruri) was investigated by using supercritical carbon dioxide (SC-CO2) with food-grade (ethanol-water) cosolvent. The quantification of excess ethanol content in the final dry extracts was conducted to determine the safety of enriched extracts. The extraction yields obtained by scale-up SFE unit were not much different compared to the predicted extraction yields with an error of 2.92%. For component contents, the scale-up extracts showed comparable quality with laboratory-scale experiments. The final dry extract showed that the excess ethanol content was 1.56% g/g extract. The fish embryo toxicity test (FETT) on the zebrafish embryos showed no toxicity effects by the extract, where the LD50 value was found to be 505.71 µg/mL. Thus, it has been proven that SFE with food-grade cosolvent is a safe extraction technique for the production of bioactive compounds from P. niruri.

Keywords: scale-up, supercritical fluid extraction, enriched extract, toxicity, ethanol content

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

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

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Authors: Dana Craciun, Daniela Dascalu, Adriana Isvoran

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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: phthalates, ADME-Tox, pharmacokinetics, biological effects

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Authors: Hicham Abidallah

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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: Metarhizium anisopliae, salvia officinalis, Schinus molle, Aphis fabae, efficiency degree

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

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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: NPs, GST, catalase, GSH, MDA, toxicity, snale and paramecium

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

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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: Peganum harmala, rat, liver, kidney, alkaloids, toxicity

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Authors: Shoukat Ali, Amjad Hussain, Latif-ur-Rehman, Sehrish Inam

Abstract:

Radiotherapy plays an important role in the management of cancer patients. Approximately 50% of the cancer patients receive radiotherapy at one point or another during the course of treatment. The entire radiotherapy treatment of curative intent is divided into different phases, depending on the histology of the tumor. The established protocols are useful in deciding the total dose, fraction size, and numbers of phases. The objective of this study was to evaluate the dosimetric differences between the conventional treatment protocols and the three-dimensional conformal simultaneously integrated boost (SIB) plans for three different tumors sites (i.e. bladder, breast, and brain). A total of 30 patients with brain, breast and bladder cancers were selected in this retrospective study. All the patients were CT simulated initially. The primary physician contoured PTV1 and PTV2 in the axial slices. The conventional doses prescribed for brain and breast is 60Gy/30 fractions, and 64.8Gy/36 fractions for bladder treatment. For the SIB plans biological effective doses (BED) were calculated for 25 fractions. The two conventional (Phase I and Phase II) and a single SIB plan for each patient were generated on Eclipse™ treatment planning system. Treatment plans were compared and analyzed for coverage index, conformity index, homogeneity index, dose gradient and organs at risk doses.In both plans 95% of PTV volume received a minimum of 95% of the prescribe dose. Dose deviation in the optic chiasm was found to be less than 0.5%. There is no significant difference in lung V20 and heart V30 in the breast plans. In the rectum plans V75%, V50% and V25% were found to be less than 1.2% different. Deviation in the tumor coverage, conformity and homogeneity indices were found to be less than 1%. SIB plans with three dimensional conformal radiotherapy technique reduce the overall treatment time without compromising the target coverage and without increasing dose to the organs at risk. The higher dose per fraction may increase the late effects to some extent. Further studies are required to evaluate the late effects with the intention of standardizing the SIB technique for practical implementation.

Keywords: coverage index, conformity index, dose gradient, homogeneity index, simultaneously integrated boost

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Authors: Muhammad Shahzad Tufail, Iram Liaqat

Abstract:

Silver nanoparticles (AgNPs) have wider biomedical applications due to their intensive antimicrobial activities. However, toxicity and side effects of nanomaterials like AgNPs is a subject of great controversy towards the further studies in this direction. In this study, biogenically synthesized AgNPs, previously characterized via ultraviolet (UV) visible spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) and fourier transform infrared spectroscopy (FTIR), were subjected to toxicity evaluation using mice model. Albino male mice (BALB/c) were administered with 50 mgkg-1, 100 mgkg-1 and 150 mgkg-1 of AgNPs, respectively, except for control for 30 days. Log-probit regression analysis was used to measure the dosage response to determine the median lethal dose (LD50). Exposure to AgNPs caused significant changes in the levels of serum AST (P ˂ 0.05) at the 100mgkg-1 and 150mgkg-1 of AgNPs exposure, while ALT and serum creatinine (P ˃ 0.05) levels remained normal. Histopathology of male albino mice liver and kidney was studied after 30 days experimental period. Results revealed that mice exposed to heavy dose (150 mgkg-1) of AgNPs showed cell distortion, necrosis and detachment of hepatocytes in the liver. Regarding kidney, at lower concentration, normal renal structure with normal glomeruli was observed. However, at higher concentration (150 mgkg-1), kidneys showed smooth surface and dark red colour with proliferation of podocytes. It can be concluded from present study that biologically synthesized AgNPs are small to be eliminated easily by kidney and therefore the liver and kidney did not show toxicity at low concentrations.

Keywords: silver nanoparticles, pseudomonas aeruginosa, male albino mice, toxicity assessment

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

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: dolichos lablab, germination, neuroprotection, trigonelline

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Authors: Zakaria Mowafy Emam Mowafy, Hamed Abd Allah Hamed, Marwa Mahmoud Abd-Elmotalb, Andrew Anis Fakhray Mosaad

Abstract:

The purpose of this paper is to determine the efficacy of polarized light therapy for chemotherapy-treated cancer patients who have oral mucositis. Methods of evaluation are the measurement of the WHO oral mucositis scale and the common toxicity criteria scale. Methods: Thirty cancer patients receiving chemotherapy (males and females) who had oral mucositis and ulceration pain, and their ages ranged from 30 to 55 years, were divided into two groups. Group (A), composed of 15 patients, received the Bioptron light therapy (BLT) in addition to the routine medical care of oral mucositis. Group (B) received only the routine medical care of oral mucositis; the duration of the BLT application was 10 minutes applied daily for 30 days. Results and conclusion: Results showed that the application of the BLT had valuable healing effects on oral mucositis in cancer patients receiving chemotherapy, as evidenced by the high decreases of the WHO oral mucositis scale and the common toxicity criteria scale.

Keywords: Bioptron light therapy, oral mucositis, WHO oral mucositis scale, common toxicity criteria scale

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Authors: Héctor González Espinosa, Ricardo Ivan Cordova Chávez, Alejandra Contreras Ramos, Itzia Irene Padilla Martínez, José Guadalupe Trujillo Ferrara, Marvin Antonio Soriano Ursúa

Abstract:

Boronic acids are able to create diester bonds with carbohydrates because of their hydroxyl groups; in nature, there are some organoborates with these characteristics, such as the calcium fructoborate, formed by the union of two fructose molecules and a boron atom, synthesized by plants. In addition, it has been observed that, in animal cells only the compounds with cis-diol functional groups are capable of linking to boric or boronic acids. The formation of these organoboron compounds could impair the physical and chemical properties of the precursors, even their acute toxicity. In this project, two carbohydrate-derived boron-containing compounds from D-fructose and D-arabinose and phenylboronic acid are analyzed by different spectroscopy techniques such as Raman, Infrared with Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) and X-ray diffraction crystallography to describe their chemical characteristics. Also, an acute toxicity test was performed to determine their LD50 using the Lorke’s method. It was confirmed by multiple spectra the formation of the adducts by the generation of the diester bonds with a β-D-pyranose of fructose and arabinose. The most prominent findings were the presence of signals corresponding to the formation of new bonds, like the stretching of B-O bonds, or the absence of signals of functional groups like the hydroxyls presented in the reagents used for the synthesis of the adducts. The NMR spectra yielded information about the stereoselectivity in the synthesis reaction, observed by the interaction of the protons and their vicinal atoms in the anomeric and second position carbons; but also, the absence of a racemic mix by the finding of just one signal in the range for the anomeric carbon in the 13C NMR spectra of both adducts. The acute toxicity tests by the Lorke’s method showed that the LD50 value for both compounds is 1265 mg/kg. Those results let us to propose these adducts as highly safe agents for further biological evaluation with medical purposes.

Keywords: acute toxicity, adduct, boron, carbohydrate, diester bond

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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: MWNT-COOH, functionalization, phenylisocyanate, phenylisothiocyanate, 1, 4-phenylendiamine, toxicity investigation

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

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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, mixtures, fertility, oxidative stress

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Authors: Sean Hall

Abstract:

Nanosystems for drug delivery are not new; as medicines evolve, so too does the desire to deliver a more targeted, patient-compliant medicine. Though, historically the widespread use of nanosystems for drug delivery has been fouled by non-replicability, scalability, toxicity issues, and economics. Examples include steps of manufacture and thus cost to manufacture, toxicity for nanoparticle scaffolding, autoimmune response, and considerable technical expertise for small non-commercial yields. This, unfortunately, demonstrates the not-so-obvious chasm between science and drug formulation for regulatory approval. Regardless there is a general and global desire to improve the delivery of medicines, reduce potential side effect profiles, promote increased patient compliance, and increase and/or speed public access to medicine availability. In this paper, the author will discuss NanoCelle®, a nano-delivery platform that specifically addresses degradation and solubility issues that expands from fundamental micellar preparations. NanoCelle® has been deployed in several Australian listed medicines and is in use of several drug candidates across small molecules, with research endeavors now extending into large molecules. The author will discuss several research initiatives as they relate to NanoCelle® to demonstrate similarities seen in various drug substances; these examples will include both in vitro and in vivo work.

Keywords: NanoCelle®, micellar, degradation, solubility, toxicity

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Authors: Devasis Ghosh

Abstract:

The main hindrance to total cure of cancer is a) the failure to control continued production of cancer cells, b) its sustenance and c) its metastasis. This review study has tried to address this issue of total cancer cure in a more innovative way. A 10-pronged “CRAB METHOD”, a novel holistic scientific approach of Cancer treatment has been hypothesized in this paper. Apart from available Chemotherapy, Radiotherapy and Oncosurgery, (which shall not be discussed here), seven other points of interference and treatment has been suggested, i.e. 1. Efficient stress management. 2. Dampening of ATF3 expression. 3. Selective inhibition of Platelet Activity. 4. Modulation of serotonin production, metabolism and 5HT receptor antagonism. 5. Auxin, its anti-proliferative potential and its modulation. 6. Melatonin supplementation because of its oncostatic properties. 7. HDAC Inhibitors especially valproic acid use due to its apoptotic role in many cancers. If all the above stated seven steps are thoroughly taken care of at the time of initial diagnosis of cancer along with the available treatment modalities of Chemotherapy, Radiotherapy and Oncosurgery, then perhaps, the morbidity and mortality rate of cancer may be greatly reduced.

Keywords: ATF3 dampening, auxin modulation, cancer, platelet activation, serotonin, stress, valproic acid

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