Journal of Toxicology http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Neuroprotective Effects of Alpha-Mangostin on MPP+-Induced Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells Tue, 18 Aug 2015 09:48:17 +0000 http://www.hindawi.com/journals/jt/2015/919058/ In vitro studies have shown that extracts from mangosteen (Garcinia mangostana Linn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson’s disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP+-induced apoptosis. The effects of alpha-mangostin on MPP+-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real-time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP+ on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP+. Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha-mangostin and MPP+. The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP+ treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP+-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation. Prachya Janhom and Permphan Dharmasaroja Copyright © 2015 Prachya Janhom and Permphan Dharmasaroja. All rights reserved. Circadian Rhythms and Breast Cancer: The Role of Per2 in Doxorubicin-Induced Cell Death Tue, 11 Aug 2015 10:22:28 +0000 http://www.hindawi.com/journals/jt/2015/392360/ Mammalian circadian rhythms form an integral physiological system allowing for the synchronisation of all metabolic processes to daily light/dark cycles, thereby optimising their efficacy. Circadian disruptions have been implicated in the onset and progression of various cancers, including those arising in the breast. Several links between the circadian protein Per2 and DNA damage responses exist. Aberrant Per2 expression results in potent downstream effects on both cell cycle and apoptotic targets, suggestive of a tumour suppressive role for Per2. Due to the severe dose limiting side effects associated with current chemotherapeutic strategies, including the use of doxorubicin, a need for more effective adjuvant therapies to increase cancer cell susceptibility has arisen. This study was therefore aimed at characterizing the role of Per2 in normal breast epithelia (MCF-12A) and in ER− breast cancer cells (MDA-MB-231) and also at determining the role of Per2 in doxorubicin-induced cell death. In both cell lines Per2 protein expression displayed a 24-hour circadian rhythm in both cell lines. Per2 was located predominantly in the cytoplasm, with nuclear localization observed with lower cytoplasmic fluorescent intensities. Our results show that Per2 silencing effectively sensitizes the chemoresistant MDA-MB-231 breast cancer cells to the cytotoxic effects of doxorubicin. Megan I. Mitchell and Anna-Mart Engelbrecht Copyright © 2015 Megan I. Mitchell and Anna-Mart Engelbrecht. All rights reserved. Intoxication by Cyanide in Pregnant Sows: Prenatal and Postnatal Evaluation Tue, 26 May 2015 14:17:25 +0000 http://www.hindawi.com/journals/jt/2015/407654/ Cyanide is a ubiquitous chemical in the environment and has been associated with many intoxication episodes; however, little is known about its potentially toxic effects on development. The aim of this study was to evaluate the effects of maternal exposure to potassium cyanide (KCN) during pregnancy on both sows and their offspring. Twenty-four pregnant sows were allocated into four groups that orally received different doses of KCN (0.0, 2.0, 4.0, and 6.0 mg/kg of body weight) from day 21 of pregnancy to term. The KCN-treated sows showed histological lesions in the CNS, thyroid follicle enlargement, thyroid epithelial thickening, colloid reabsorption changes, and vacuolar degeneration of the renal tubular epithelium. Sows treated with 4.0 mg/kg KCN showed an increase in the number of dead piglets at birth. Weaned piglets from all KCN-treated groups showed histological lesions in the thyroid glands with features similar to those found in their mothers. The exposure of pregnant sows to cyanide thus caused toxic effects in both mothers and piglets. We suggest that swine can serve as a useful animal model to assess the neurological, goitrogenic, and reproductive effects of cyanide toxicosis. André T. Gotardo, Isis M. Hueza, Helena Manzano, Viviane M. Maruo, Paulo C. Maiorka, and Silvana L. Górniak Copyright © 2015 André T. Gotardo et al. All rights reserved. Species Differences in Paraoxonase Mediated Hydrolysis of Several Organophosphorus Insecticide Metabolites Sun, 15 Feb 2015 08:52:47 +0000 http://www.hindawi.com/journals/jt/2015/470189/ Paraoxonase (PON1) is a calcium dependent enzyme that is capable of hydrolyzing organophosphate anticholinesterases. PON1 activity is present in most mammals and previous research established that PON1 activity differs depending on the species. These studies mainly used the organophosphate substrate paraoxon, the active metabolite of the insecticide parathion. Using serum PON1 from different mammalian species, we compared the hydrolysis of paraoxon with the hydrolysis of the active metabolites (oxons) of two additional organophosphorus insecticides, methyl parathion and chlorpyrifos. Paraoxon hydrolysis was greater than that of methyl paraoxon, but the level of activity between species displayed a similar pattern. Regardless of the species tested, the hydrolysis of chlorpyrifos-oxon was significantly greater than that of paraoxon or methyl paraoxon. These data indicate that chlorpyrifos-oxon is a better substrate for PON1 regardless of the species. The pattern of species differences in PON1 activity varied with the change in substrate to chlorpyrifos-oxon from paraoxon or methyl paraoxon. For example, the sex difference observed here and reported elsewhere in the literature for rat PON1 hydrolysis of paraoxon was not present when chlorpyrifos-oxon was the substrate. Russell L. Carr, Mary Beth Dail, Howard W. Chambers, and Janice E. Chambers Copyright © 2015 Russell L. Carr et al. All rights reserved. Fertilizers and Mixed Crop Cultivation of Chromium Tolerant and Sensitive Plants under Chromium Toxicity Thu, 29 Jan 2015 14:17:50 +0000 http://www.hindawi.com/journals/jt/2015/367217/ Zea mays (maize) and Vigna radiata (green gram) are found to be the chromium (Cr) tolerant and sensitive plants, respectively. In the present paper, we investigate the reduction of the toxicity of Cr in the sensitive plants by the mixed crop cultivation in the field using various amendments. Further, the potassium dichromate was used as the source of hexavalent Cr. The results indicated that Cr adversely affects both the growth and yield of plants. The soil properties vary with Cr and different fertilizer amendments and the yield of both plants were affected by Cr. We conclude that metal accumulation of seeds of green gram was higher than corn and the application of single fertilizer either farm yard manure (FYM) or nitrogen, phosphorous, and potassium (NPK) enhances the growth and yield of both the tolerant and sensitive plants in the mixed crop cultivations. B. Dheeba, P. Sampathkumar, and K. Kannan Copyright © 2015 B. Dheeba et al. All rights reserved. Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines Wed, 21 Jan 2015 07:06:21 +0000 http://www.hindawi.com/journals/jt/2015/573701/ The association of autism spectrum disorders with oxidative stress, redox imbalance, and mitochondrial dysfunction has become increasingly recognized. In this study, extracellular flux analysis was used to compare mitochondrial respiration in lymphoblastoid cell lines (LCLs) from individuals with autism and unaffected controls exposed to ethylmercury, an environmental toxin known to deplete glutathione and induce oxidative stress and mitochondrial dysfunction. We also tested whether pretreating the autism LCLs with N-acetyl cysteine (NAC) to increase glutathione concentrations conferred protection from ethylmercury. Examination of 16 autism/control LCL pairs revealed that a subgroup (31%) of autism LCLs exhibited a greater reduction in ATP-linked respiration, maximal respiratory capacity, and reserve capacity when exposed to ethylmercury, compared to control LCLs. These respiratory parameters were significantly elevated at baseline in the ethylmercury-sensitive autism subgroup as compared to control LCLs. NAC pretreatment of the sensitive subgroup reduced (normalized) baseline respiratory parameters and blunted the exaggerated ethylmercury-induced reserve capacity depletion. These findings suggest that the epidemiological link between environmental mercury exposure and an increased risk of developing autism may be mediated through mitochondrial dysfunction and support the notion that a subset of individuals with autism may be vulnerable to environmental influences with detrimental effects on development through mitochondrial dysfunction. Shannon Rose, Rebecca Wynne, Richard E. Frye, Stepan Melnyk, and S. Jill James Copyright © 2015 Shannon Rose et al. All rights reserved. Cytotoxicity and Genotoxicity of Panel of Single- and Multiwalled Carbon Nanotubes: In Vitro Effects on Normal Syrian Hamster Embryo and Immortalized V79 Hamster Lung Cells Mon, 08 Dec 2014 12:13:55 +0000 http://www.hindawi.com/journals/jt/2014/872195/ Carbon nanotubes (CNTs) belong to a specific class of nanomaterials with unique properties. Because of their anticipated use in a wide range of industrial applications, their toxicity is of increasing concern. In order to determine whether specific physicochemical characteristics of CNTs are responsible for their toxicological effects, we investigated the cytotoxic and genotoxic effects of eight CNTs representative of each of the commonly encountered classes: single- SW-, double- DW-, and multiwalled (MW) CNTs, purified and raw. In addition, because most previous studies of CNT toxicity were conducted on immortalized cell lines, we decided to compare results obtained from V79 cells, an established cell line, with results from SHE (Syrian hamster embryo) cells, an easy-to-handle normal cell model. After 24 hours of treatment, MWCNTs were generally found to be more cytotoxic than SW- or DWCNTs. MWCNTs also provoked more genotoxic effects. No correlation could be found between CNT genotoxicity and metal impurities, length, surface area, or induction of cellular oxidative stress, but genotoxicity was seen to increase with CNT width. The toxicity observed for some CNTs leads us to suggest that they might also act by interfering with the cell cycle, but no significant differences were observed between normal and immortalized cells. C. Darne, F. Terzetti, C. Coulais, C. Fontana, S. Binet, L. Gaté, and Y. Guichard Copyright © 2014 C. Darne et al. All rights reserved. Anion Gap Toxicity in Alloxan Induced Type 2 Diabetic Rats Treated with Antidiabetic Noncytotoxic Bioactive Compounds of Ethanolic Extract of Moringa oleifera Mon, 08 Dec 2014 07:12:26 +0000 http://www.hindawi.com/journals/jt/2014/406242/ Moringa oleifera (MO) is used for a number of therapeutic purposes. This raises the question of safety and possible toxicity. The objective of the study was to ascertain the safety and possible metabolic toxicity in comparison with metformin, a known drug associated with acidosis. Animals confirmed with diabetes were grouped into 2 groups. The control group only received oral dose of PBS while the test group was treated with ethanolic extract of MO orally twice daily for 5-6 days. Data showed that the extract significantly lowered glucose level to normal values and did not cause any significant cytotoxicity compared to the control group (); there was no gain in weight between the MO treated and the control groups (). However, data showed that treatment with an ethanolic extract of MO caused a decrease in bicarbonate (), and more than twofold increase in anion gap (); metformin treatment also decreased bicarbonate () and resulted in a threefold increase in anion gap (). Conclusively, these data show that while MO appears to have antidiabetic and noncytotoxic properties, it is associated with statistically significant anion gap acidosis in alloxan induced type 2 diabetic rats. Maxwell Omabe, Chibueze Nwudele, Kenneth Nwobini Omabe, and Albert Egwu Okorocha Copyright © 2014 Maxwell Omabe et al. All rights reserved. Camel Milk Beneficial Effects on Treating Gentamicin Induced Alterations in Rats Wed, 03 Dec 2014 00:10:09 +0000 http://www.hindawi.com/journals/jt/2014/917608/ The potential effect of camel milk (CM) against gentamicin (GM) induced biochemical changes in the rat serum was evaluated. Four groups of six albino rats were used for control, CM fed, injected with GM(i.p.), and then fed and injected with GM. The results showed that the administration of GM significantly altered the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activity in rat serum. CM restored these parameters to almost their normal range in group IV. Additionally, the present study showed that injection of rats with gentamicin caused an increase in malondialdehyde (MDA) and myeloperoxidase (MPO) activity while the antioxidant enzymes like superoxide dismutase (SOD) and glutathione s-transferase (GST) activity decreased significantly (). Administration of CM significantly () inhibited the formation of MDA and activity of MPO and upregulated the antioxidant enzymes (SOD and GST) activity. The overall findings of this study demonstrated that pretreatment with CM gave protection against GM induced hepatic damage possibly by inhibiting oxidative stress and inflammation, and hence camel milk can be identified as a new therapeutic agent. Abdulrahman K. Al-Asmari, R. Abbasmanthiri, Abdulrahman M. Al-Elewi, Saud Al-Omani, Saeed Al-Asmary, and Sarah A. Al-Asmari Copyright © 2014 Abdulrahman K. Al-Asmari et al. All rights reserved. Trace and Essential Elements Analysis in Cymbopogon citratus (DC.) Stapf Samples by Graphite Furnace-Atomic Absorption Spectroscopy and Its Health Concern Mon, 01 Dec 2014 00:10:07 +0000 http://www.hindawi.com/journals/jt/2014/690758/ Cymbopogon citratus (DC.) Stapf commonly known as lemon grass is used extensively as green tea and even as herbal tea ingredient across the world. Plants have the ability to uptake metals as nutrient from the soil and its environment which are so essential for their physiological and biochemical growth. Concentrations of these twelve trace elements, namely, Mg, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Mo, As, Cd, and Pb, are analysed by graphite furnace-atomic absorption spectroscopy (GF-AAS) and are compared with the permissible limits of FAO/WHO, ICMR, and NIH, USA, which are found to be within permissible limits. Toxic metals like As, Cd, and Pb, analysed are within the tolerable daily diet limit and at low concentration. Jasha Momo H. Anal Copyright © 2014 Jasha Momo H. Anal. All rights reserved. Conditioned Medium Reconditions Hippocampal Neurons against Kainic Acid Induced Excitotoxicity: An In Vitro Study Sun, 23 Nov 2014 00:00:00 +0000 http://www.hindawi.com/journals/jt/2014/194967/ Stem cell therapy is gaining attention as a promising treatment option for neurodegenerative diseases. The functional efficacy of grafted cells is a matter of debate and the recent consensus is that the cellular and functional recoveries might be due to “by-stander” effects of grafted cells. In the present study, we investigated the neuroprotective effect of conditioned medium (CM) derived from human embryonic kidney (HEK) cells in a kainic acid (KA) induced hippocampal degeneration model system in in vitro condition. Hippocampal cell line was exposed to KA (200 µM) for 24 hrs (lesion group) whereas, in the treatment group, hippocampal cell line was exposed to KA in combination with HEK-CM (KA + HEK-CM). We observed that KA exposure to cells resulted in significant neuronal loss. Interestingly, HEK-CM cotreatment completely attenuated the excitotoxic effects of KA. In HEK-CM cotreatment group, the cell viability was ~85–95% as opposed to 47% in KA alone group. Further investigation demonstrated that treatment with HEK-CM stimulated the endogenous cell survival factors like brain derived neurotrophic factors (BDNF) and antiapoptotic factor Bcl-2, revealing the possible mechanism of neuroprotection. Our results suggest that HEK-CM protects hippocampal neurons against excitotoxicity by stimulating the host’s endogenous cell survival mechanisms. Pradeep Kumar K. Bevinahal, Chaitra Venugopal, Harish Chandra Prasad S. Yencharla, Shashank Chandanala, Raju R. Trichur, Sathyaprabha N. Talakad, Ramesh R. Bhonde, and Anandh Dhanushkodi Copyright © 2014 Pradeep Kumar K. Bevinahal et al. All rights reserved. Ameliorating Effects of Iron and Zinc on Vigna mungo L. Treated with Tannery Effluent Wed, 19 Nov 2014 00:00:00 +0000 http://www.hindawi.com/journals/jt/2014/910497/ Different dilutions, that is, 25, 50, 75, and 100%, of tannery effluent (TE) were chosen for the present study to assess the phytotoxic effects on Vigna mungo L. For amelioration purposes, different levels and combinations of iron and zinc were supplied to the plants along with 50% TE that is chosen on the basis of prior test under Petri dish culture. Cytotoxic and biochemical analysis and plant tolerance index (PTI) of plant were observed. Mitotic index deceased with increase in effluent concentration whereas abnormality % was increased. The pigments (chlorophyll a, total, and carotenoids) were decreased with increasing treatment levels of TE at both growth stages. However, carotenoid content increased significantly at all dilution levels of TE after first growth stage. Chlorophyll b was increased significantly after 35 days of growth but decreased after 70 days. The protein contents were also significantly decreased with increase in all TE treatments and increased significantly in zinc recovery treatments. Activities of catalase and peroxidase enzymes were significantly affected and increased significantly with effluent treatments. PTI showed an enhanced tolerance capacity of plant with treatment of iron and zinc. A negative correlation was found () between plant height and different dilutions of effluent whereas it was positively correlated () with iron and zinc treatments. The study represents the ameliorative effect of iron and zinc for phytotoxic damage in V. mungo caused by tannery effluent. Shefali Srivastava, Kumkum Mishra, and Pramod Kumar Tandon Copyright © 2014 Shefali Srivastava et al. All rights reserved. Xylazine as a Drug of Abuse and Its Effects on the Generation of Reactive Species and DNA Damage on Human Umbilical Vein Endothelial Cells Tue, 11 Nov 2014 06:57:20 +0000 http://www.hindawi.com/journals/jt/2014/492609/ Human xylazine (XYL) abuse among addicts has received great interest due to its potential toxic effects upon addicts and the need to understand the mechanism of action associated with the potential health effects. XYL is an alpha-2 agonist restricted to veterinarian applications, without human medical applications. Our previous work demonstrated that XYL and its combination with cocaine (COC) and/or 6-monoacetylmorphine (6-MAM) induce cell death through an apoptotic mechanism. The aim of this study was to determine the effect of xylazine on the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as well as DNA damage on endothelial cell. Human umbilical vein endothelial cells (HUVEC) were treated with XYL (60 μM), COC (160 μM), 6-MAM (160 μM), camptothecin (positive control, 50 μM), XYL/COC (50 μM), XYL/6-MAM (50 μM), and XYL/COC/6-MAM (40 μM) for a period of 24 hours. Generation of intracellular ROS, RNS, and DNA fragmentation were analyzed using a fluorometric assay. Results reveal that XYL and 6-MAM increase levels of ROS; no induction of RNS production was observed. The combination of these drugs shows significant increase in DNA fragmentation in G2/M phase, while XYL, COC, and 6-MAM, without combination, present higher DNA fragmentation in G0/G1 phase. These findings support that these drugs and their combination alter important biochemical events aligned with an apoptotic mechanism of action in HUVEC. Luz Silva-Torres, Christian Veléz, Lyvia Álvarez, and Beatriz Zayas Copyright © 2014 Luz Silva-Torres et al. All rights reserved. In Vitro Reporter Assays for Screening of Chemicals That Disrupt Androgen Signaling Sun, 09 Nov 2014 09:45:13 +0000 http://www.hindawi.com/journals/jt/2014/701752/ Endocrine disruptive chemicals (EDCs) modulate hormone signaling and cause developmental and reproductive anomalies. Today, there is a global concern regarding endocrine disruption effects, particularly those mediated by the androgen receptor (AR). Androgen or male hormones are critical for the development and maintenance of male characteristics and numerous EDCs exist in the environment with the potential to disrupt androgen action. The threat is more during critical developmental windows when there is increased sensitivity to these compounds. Timely screening and detection of the EDCs is essential to minimize deleterious effects produced by these toxic chemicals. As a first line of screening, in vitro transcription assays are very useful due to their speed, convenience, and cost effectiveness. In this paper, recent in vitro reporter assays for detecting androgenic or antiandrogenic activity of EDCs have been reviewed. Two important cell systems used for this purpose, namely, the mammalian or yeast cell systems, have been discussed. Use of reporter genes such as bacterial luciferase (lux) and green fluorescent protein (gfp) has significantly improved speed and sensitivity of detection. Also, many of the current reporter assay systems can be used in a high throughput format allowing speedy evaluation of multiple potential EDCs at a lower price. Gargi Bagchi Bhattacharjee and S. M. Paul Khurana Copyright © 2014 Gargi Bagchi Bhattacharjee and S. M. Paul Khurana. All rights reserved. Lipid Profile and Oxidative Stress Markers in Wistar Rats following Oral and Repeated Exposure to Fijk Herbal Mixture Mon, 20 Oct 2014 09:34:56 +0000 http://www.hindawi.com/journals/jt/2014/876035/ This study determined the effect of the oral and repeated administration of Fijk herbal mixture on rat biochemical and morphological parameters. Twenty-four Wistar rats were distributed into four groups of 6. Group A served as control and received oral administration of distilled water daily. The experimental groups B, C, and D were daily and orally exposed to Fijk herbal mixture at 15, 30, and 45 mg/kg, respectively. Treatments lasted for 21 days. The rats were sacrificed under mild diethyl ether anesthesia 24 hr after cessation of treatment. The blood and liver samples were collected and used for the biochemical and morphological analyses. Oral exposure to Fijk caused elevated levels of rat plasma ALT, AST, triglycerides, LDL, and MDA. In contrast, rat plasma HDL, GSH, and ALP levels were lowered by Fijk oral exposure. Also, the herbal remedy caused a dose-dependent elevation in the plasma atherogenic index. The histopathology examinations of rat liver sections revealed inimical cellular alterations caused by repeated exposure to Fijk. Study provides evidence that oral and repeated exposure to Fijk in rats raised the atherogenic index and potentiated oxidative stress as well as hepatic injury. Oluyomi Stephen Adeyemi and Bukola Temitope Orekoya Copyright © 2014 Oluyomi Stephen Adeyemi and Bukola Temitope Orekoya. All rights reserved. Impairment of Hepatic and Renal Functions by 2,5-Hexanedione Is Accompanied by Oxidative Stress in Rats Wed, 15 Oct 2014 00:00:00 +0000 http://www.hindawi.com/journals/jt/2014/239240/ 2,5-Hexanedione (2,5-HD) is the toxic metabolite of n-hexane which is widely used as solvent in numerous industries. The present study elucidated the precise mechanism of 2,5-HD in hepatorenal toxicity by determining the involvement of oxidative stress in rats. Adult male Wistar rats were exposed to 0, 0.25, 0.5, and 1% 2,5-HD in drinking water for 21 days. Exposure to 2,5-HD caused liver and kidney atrophy evidenced by significant elevation in serum aminotransferases, alkaline phosphatase, albumin, bilirubin, urea, creatinine, and electrolytes levels compared with control. The marked dose-dependent increase in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) was accompanied with significant decrease in high-density lipoprotein (HDL) levels in 2,5-HD-exposed animals when compared with the control. Administration of 2,5-HD significantly diminished glutathione (GSH) level but increased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione-S-transferase (GST) concomitantly with marked elevation in hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels in liver and kidney of the treated groups compared with control. These findings suggest that undue exposure to 2,5-HD at environmentally relevant levels may impair liver and kidney functions through induction of oxidative stress. Isaac A. Adedara, Amos O. Abolaji, Blessing E. Odion, Isioma J. Okwudi, Abiola A. Omoloja, and Ebenezer O. Farombi Copyright © 2014 Isaac A. Adedara et al. All rights reserved. Modeling In Vitro Cellular Responses to Silver Nanoparticles Thu, 09 Oct 2014 07:06:51 +0000 http://www.hindawi.com/journals/jt/2014/852890/ Engineered nanoparticles (NPs) have been widely demonstrated to induce toxic effects to various cell types. In vitro cell exposure systems have high potential for reliable, high throughput screening of nanoparticle toxicity, allowing focusing on particular pathways while excluding unwanted effects due to other cells or tissue dosimetry. The work presented here involves a detailed biologically based computational model of cellular interactions with NPs; it utilizes measurements performed in human cell culture systems in vitro, to develop a mechanistic mathematical model that can support analysis and prediction of in vivo effects of NPs. The model considers basic cellular mechanisms including proliferation, apoptosis, and production of cytokines in response to NPs. This new model is implemented for macrophages and parameterized using in vitro measurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includes in vitro cellular dosimetry due to nanoparticle transport and transformation. Furthermore, the model developed here optimizes the essential cellular parameters based on in vitro measurements, and provides a “stepping stone” for the development of more advanced in vivo models that will incorporate additional cellular and NP interactions. Dwaipayan Mukherjee, Steven G. Royce, Srijata Sarkar, Andrew Thorley, Stephan Schwander, Mary P. Ryan, Alexandra E. Porter, Kian Fan Chung, Teresa D. Tetley, Junfeng Zhang, and Panos G. Georgopoulos Copyright © 2014 Dwaipayan Mukherjee et al. All rights reserved. Aluminum-Induced Entropy in Biological Systems: Implications for Neurological Disease Thu, 02 Oct 2014 12:36:06 +0000 http://www.hindawi.com/journals/jt/2014/491316/ Over the last 200 years, mining, smelting, and refining of aluminum (Al) in various forms have increasingly exposed living species to this naturally abundant metal. Because of its prevalence in the earth’s crust, prior to its recent uses it was regarded as inert and therefore harmless. However, Al is invariably toxic to living systems and has no known beneficial role in any biological systems. Humans are increasingly exposed to Al from food, water, medicinals, vaccines, and cosmetics, as well as from industrial occupational exposure. Al disrupts biological self-ordering, energy transduction, and signaling systems, thus increasing biosemiotic entropy. Beginning with the biophysics of water, disruption progresses through the macromolecules that are crucial to living processes (DNAs, RNAs, proteoglycans, and proteins). It injures cells, circuits, and subsystems and can cause catastrophic failures ending in death. Al forms toxic complexes with other elements, such as fluorine, and interacts negatively with mercury, lead, and glyphosate. Al negatively impacts the central nervous system in all species that have been studied, including humans. Because of the global impacts of Al on water dynamics and biosemiotic systems, CNS disorders in humans are sensitive indicators of the Al toxicants to which we are being exposed. Christopher A. Shaw, Stephanie Seneff, Stephen D. Kette, Lucija Tomljenovic, John W. Oller Jr., and Robert M. Davidson Copyright © 2014 Christopher A. Shaw et al. All rights reserved. Determination of Mercury Exposure among Dental Health Workers in Nakhon Si Thammarat Province, Thailand Wed, 01 Oct 2014 13:05:36 +0000 http://www.hindawi.com/journals/jt/2014/401012/ Objectives. The main objective of this study was to assess the mercury exposure levels in dental health workers that work in dental clinics. The study evaluated the airborne and urinary mercury levels, the type of work done in the clinic, and the effect of mercury exposure on health of dental health workers. Material and Methods. A case-control study was conducted with 124 exposed and 124 matched nonexposed subjects. Personal and area samplings were conducted to quantify mercury concentrations by solid sorbent tube. Urine samples were collected to determine mercury levels by cold-vapor atomic absorption spectrometer mercury analyzer. Results and Discussion. 17.6% () of the air samples were higher than the occupational exposure limit (OEL). A multiple regression model was constructed. Significant predictors of urinary mercury levels included dietary consumption (fish or seafood), duration of work (yrs), work position, personal protection equipment used (PPE), and personal hygiene behaviors. Significant correlations were observed between mercury levels in urine and mercury in storage areas (, ) and between mercury levels in urine and airborne mercury in personal samplings (, ). Conclusion. Improvements in working conditions, occupational health training, and PPE use are recommended to reduce mercury exposure. Somsiri Decharat, Piriyaluk Phethuayluk, Supandee Maneelok, and Phayong Thepaksorn Copyright © 2014 Somsiri Decharat et al. All rights reserved. Effects of Short Term Exposure of Atrazine on the Liver and Kidney of Normal and Diabetic Rats Mon, 29 Sep 2014 11:03:36 +0000 http://www.hindawi.com/journals/jt/2014/536759/ The present study evaluates the effects of short term (15 days) exposure of low dose (300 μg kg−1) of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) on antioxidant status and markers of liver and kidney damage in normal (nondiabetic) and diabetic male Wistar rats. Rats were divided into four groups: Group I as normal control, Group II as atrazine treated, Group III as diabetic control, and Group IV as atrazine treated diabetic rats. Atrazine administration resulted in increased MDA concentration as well as increased activities of SOD, CAT, and GPx in both liver and kidney of atrazine treated and atrazine treated diabetic rats. However, GSH level was decreased in both liver and kidney of atrazine treated and atrazine treated diabetic rats. Atrazine administration led to significant increase in liver damage biomarkers such as AST, ALT, and ALP as well as kidney damage biomarkers such as creatinine and urea in both normal and diabetic rats, but this increase was more pronounced in diabetic rats when compared to normal rats. In conclusion, the results of the present study demonstrate that short term exposure of atrazine at a dose of 300 μg kg−1 could potentially induce oxidative damage in liver and kidney of both normal and diabetic rats. Dinesh Babu Jestadi, Alugoju Phaniendra, Undru Babji, Thupakula Srinu, Bhavatharini Shanmuganathan, and Latha Periyasamy Copyright © 2014 Dinesh Babu Jestadi et al. All rights reserved. Antigenotoxic Effect of Curcumin and Carvacrol against Parathion Induced DNA Damage in Cultured Human Peripheral Blood Lymphocytes and Its Relation to GSTM1 and GSTT1 Polymorphism Thu, 25 Sep 2014 09:31:50 +0000 http://www.hindawi.com/journals/jt/2014/404236/ In recent years, the use of organophosphorus pesticides has been extensively increased and these compounds signify a major class of agricultural pesticides today. We studied antigenotoxic potential of curcumin and carvacrol against the parathion induced DNA damage in cultured peripheral blood lymphocytes using sister chromatid exchanges as a biomarker of genotoxicity. Heparinised fresh blood from healthy individuals was treated with 2.5 μg/mL concentration of parathion in presence of curcumin and carvacrol in order to observe the antigenotoxic potential of both curcumin and carvacrol. Significant reduction was observed in the frequencies of SCEs in presence of 10 μg/mL and 15 μg/mL concentrations of curcumin as compared to parathion exposed sample. Similarly carvacrol had significant antigenotoxic effect at the concentrations of 2.5 μg/mL and 5.0 μg/mL against the parathion. We also studied the effect of GSTT1 and GSTM1 on genotoxicity of parathion and antigenotoxic potential of curcumin and carvacrol. We did not observe any significant effect of GSTT1 and GSTM1 polymorphism on genotoxicity of parathion and antigenotoxic potential of curcumin and carvacrol. Neeraj Kumar, Anita Yadav, Sachin Gulati, Kanupriya, Neeraj Aggarwal, and Ranjan Gupta Copyright © 2014 Neeraj Kumar et al. All rights reserved. Proliferation and 1/2 Cytokine Production in Human Peripheral Blood Mononuclear Cells after Treatment with Cypermethrin and Mancozeb In Vitro Thu, 18 Sep 2014 07:07:52 +0000 http://www.hindawi.com/journals/jt/2014/308286/ In recent times, human cell-based assays are gaining attention in assessments of immunomodulatory effects of chemicals. In the study here, the possible effects of cypermethrin and mancozeb on lymphocyte proliferation and proinflammatory (tumor necrosis factor (TNF-) ) and immunoregulatory cytokine (interferon- (IFN-) , interleukins (IL) 2, 4, 6, and 10) formation in vitro were investigated. Human peripheral blood mononuclear cells (PBMC) were isolated and exposed for 6 hr to noncytotoxic doses (0.45–30 µM) of cypermethrin or mancozeb in the presence of activating rat S9 fraction. Cultures were then further incubated for 48 or 72 hr in fresh medium containing phytohemagglutinin (10 µg/mL) to assess, respectively, effects on cell proliferation (BrdU-ELISA method) and cytokine formation (flow cytometric bead immunoassays). Mancozeb induced dose-dependent increases in lymphocyte proliferation, inhibition of production of TNF and the 2 cytokines IL-6 and IL-10, and an increase in IFN (1 cytokine) production (at least 2-fold compared to control); mancozeb also induced inhibition of IL-4 (2) and stimulated IL-2 (1) production, albeit only in dose-related manners for each. In contrast, cypermethrin exposure did not cause significant effects on proliferation or cytokine profiles. Further studies are needed to better understand the functional significance of our in vitro findings. Rajesh Mandarapu, Rajanna Ajumeera, Vijayalakshmi Venkatesan, and Balakrishna Murthy Prakhya Copyright © 2014 Rajesh Mandarapu et al. All rights reserved. Kolaviron and L-Ascorbic Acid Attenuate Chlorambucil-Induced Testicular Oxidative Stress in Rats Wed, 17 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/jt/2014/587015/ Chlorambucil (4-[4-[bis(2-chloroethyl)amino]phenyl]butanoic acid) is an alkylating agent, indicated in chronic lymphocytic leukaemia. Kolaviron (KV), a biflavonoid complex from Garcinia kola, and L-ascorbic acid (AA) are known to protect against oxidative damage in vivo. This study evaluates the protective capacity of KV and AA on chlorambucil-induced oxidative stress in the testes of rat. Twenty male Wistar rats (180–200 g) were randomized into four groups: I: control, II: chlorambucil (0.2 mg/kg b.w.), III: 0.2 mg/kg chlorambucil and 100 mg/kg KV, and IV: 0.2 mg/kg chlorambucil and 100 mg/kg AA. After 14 days of treatments, results indicated that chlorambucil caused significant reduction () in testicular vitamin C and glutathione by 32% and 39%, respectively, relative to control. Similarly, activities of testicular GST, SOD, and CAT reduced significantly by 48%, 47%, and 49%, respectively, in chlorambucil-treated rats relative to control. Testicular MDA and activities of ALP, LDH, and ACP were increased significantly by 53%, 51%, 64%, and 70%, respectively, in the chlorambucil-treated rat. However, cotreatment with KV and AA offered protection and restored the levels of vitamin C, GSH, and MDA as well as SOD, CAT, GST, ACP, ALP, and LDH activities. Overall, kolaviron and L-ascorbic acid protected against chlorambucil-induced damage in the testes of the rat. Ebenezer Tunde Olayinka and Ayokanmi Ore Copyright © 2014 Ebenezer Tunde Olayinka and Ayokanmi Ore. All rights reserved. High Content Imaging and Analysis Enable Quantitative In Situ Assessment of CYP3A4 Using Cryopreserved Differentiated HepaRG Cells Mon, 08 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/jt/2014/291054/ High-throughput imaging-based hepatotoxicity studies capable of analyzing individual cells in situ hold enormous promise for drug safety testing but are frequently limited by a lack of sufficient metabolically competent human cells. This study examined cryopreserved HepaRG cells, a human liver cell line which differentiates into both hepatocytes and biliary epithelial cells, to determine if these cells may represent a suitable metabolically competent cellular model for novel High Content Analysis (HCA) applications. Characterization studies showed that these cells retain many features characteristic of primary human hepatocytes and display significant CYP3A4 and CYP1A2 induction, unlike the HepG2 cell line commonly utilized for HCA studies. Furthermore, this study demonstrates that CYP3A4 induction can be quantified via a simple image analysis-based method, using HepaRG cells as a model system. Additionally, data demonstrate that the hepatocyte and biliary epithelial subpopulations characteristic of HepaRG cultures can be separated during analysis simply on the basis of nuclear size measurements. Proof of concept studies with fluorescent cell function reagents indicated that further multiparametric image-based assessment is achievable with HepaRG. In summary, image-based screening of metabolically competent human hepatocyte models cells such as HepaRG offers novel approaches for hepatotoxicity assessment and improved drug screening tools. Aarati R. Ranade, Melinda S. Wilson, Amy M. McClanahan, and Andrew J. Ball Copyright © 2014 Aarati R. Ranade et al. All rights reserved. Resveratrol Sensitizes Selectively Thyroid Cancer Cell to 131-Iodine Toxicity Wed, 03 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/jt/2014/839597/ Background. In this study, the radiosensitizing effect of resveratrol as a natural product was investigated on cell toxicity induced by 131I in thyroid cancer cell. Methods. Human thyroid cancer cell and human nonmalignant fibroblast cell (HFFF2) were treated with 131I and/or resveratrol at different concentrations for 48 h. The cell proliferation was measured by determination of the percent of the survival cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results. Findings of this study show that resveratrol enhanced the cell death induced by 131I on thyroid cancer cell. Also, resveratrol exhibited a protective effect on normal cells against 131I toxicity. Conclusion. This result indicates a promising effect of resveratrol on improvement of cellular toxicity during iodine therapy. Seyed Jalal Hosseinimehr and Seyed Amir Hossein Hosseini Copyright © 2014 Seyed Jalal Hosseinimehr and Seyed Amir Hossein Hosseini. All rights reserved. The Toxic Effect of Manganese on the Acetylcholinesterase Activity in Rat Brains Tue, 26 Aug 2014 12:31:52 +0000 http://www.hindawi.com/journals/jt/2014/946372/ Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. Accumulation of manganese damages central nervous system and causes Parkinson’s disease-like syndrome called manganism. Mn neurotoxicity has been suggested to involve an imbalance between the DAergic and cholinergic systems. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated by changing of AChE activity that resulted in oxidative stress. Therefore we focused the effect of Mn in AChE activity in the rat’s brain by MnCl2 injection intraperitoneally and analyzed their brains after time intervals. This study used different acute doses in short time course and different chronic doses at different exposing time to investigate which of them (exposing dose or time) is more important in Mn toxic effect. Results showed toxic effect of Mn is highly dose dependent and AChE activity in presence of chronic dose in 8 weeks reaches acute dose in only 2 days. Vahid Yousefi Babadi, Leila Sadeghi, Kobra Shirani, Ali Akbar Malekirad, and Mohammad Rezaei Copyright © 2014 Vahid Yousefi Babadi et al. All rights reserved. Ecotoxicological and Genotoxic Evaluation of Buenos Aires City (Argentina) Hospital Wastewater Thu, 21 Aug 2014 10:46:58 +0000 http://www.hindawi.com/journals/jt/2014/248461/ Hospital wastewater (HWW) constitutes a potential risk to the ecosystems and human health due to the presence of toxic and genotoxic chemical compounds. In the present work we investigated toxicity and genotoxicity of wastewaters from the public hospital of Buenos Aires (Argentina). The effluent from the sewage treatment plant (STP) serving around 10 million inhabitants was also evaluated. The study was carried out between April and September 2012. Toxicity and genotoxicity assessment was performed using the green algae Pseudokirchneriella subcapitata and the Allium cepa test, respectively. Toxicity assay showed that 55% of the samples were toxic to the algae (%I of growth between 23.9 and 54.8). The A. cepa test showed that 40% of the samples were genotoxic. The analysis of chromosome aberrations (CA) and micronucleus (MN) showed no significant differences between days and significant differences between months. The sample from the STP was not genotoxic to A. cepa but toxic to the algae (%I = 41%), showing that sewage treatment was not totally effective. This study highlights the need for environmental control programs and the establishment of advanced and effective effluent treatment plants in the hospitals, which are merely dumping the wastewaters in the municipal sewerage system. Anahí Magdaleno, Ángela Beatriz Juárez, Valeria Dragani, Magalí Elizabeth Saenz, Marta Paz, and Juan Moretton Copyright © 2014 Anahí Magdaleno et al. All rights reserved. Prognostic Factors in Acute Methadone Toxicity: A 5-Year Study Tue, 12 Aug 2014 12:54:19 +0000 http://www.hindawi.com/journals/jt/2014/341826/ Background. Delayed or recurrent profound respiratory depression, ventricular dysrhythmias, acute lung injury, and death are the major complications of MTD overdose. We aimed to clarify the prognostic factors in MTD toxicity. Materials and Methods. Retrospectively, medical files of all patients poisoned by MTD and older than 12 years of age who had presented to Loghman Hakim Poison Center between 2007 and 2012 were evaluated. The data was compared between survivors and nonsurvivors. Results. Twenty-eight out of 322 patients died (mortality rate = 8.7%). MTD-related death was higher in patients with acute on chronic toxicity who were on daily dose of MTD and had ingested higher doses (in comparison to those with acute toxicity due to first-time exposure; 13% versus 6%). Renal failure was the most common medical complication related to deaths due to MTD toxicity. Conclusions. Based on previous researches, the most common cause of MTD overdose-related deaths is respiratory impairment; however, in our study, acute renal failure with or without rhabdomyolysis was the main delayed cause of deaths in MTD-poisoned patients. Antidotal therapy, early recognition, and treatment of hemodynamic compromise and rhabdomyolysis can be life-saving in these patients. Abbas Aghabiklooei, Maryam Edalatparvar, Nasim Zamani, and Babak Mostafazadeh Copyright © 2014 Abbas Aghabiklooei et al. All rights reserved. Micro- and Macroelemental Composition and Safety Evaluation of the Nutraceutical Moringa oleifera Leaves Tue, 22 Jul 2014 09:56:43 +0000 http://www.hindawi.com/journals/jt/2014/786979/ Moringa oleifera is a multipurpose plant used in Ghana and most parts of Africa. Its high mineral, protein, and vitamins content has enabled its use as a nutraceutical and panacea for various diseases. This study aimed at measuring the micro- and macroelements content of dried Moringa oleifera leaves using energy dispersive X-ray fluorescence spectroscopic (EDXRF) and assessing its toxicological effect in rats. Acute toxicity (5000 mg/kg) and a subacute toxicity studies of the leaf (40 mg/kg to 1000 mg/kg) extract were conducted in rats. Blood samples were assessed for biochemical and haematological parameters. Results showed significant levels of thirty-five (35) elements (14 macroelements and 21 microelements) in M. oleifera extract. There were no observed overt adverse reactions in the acute and subacute studies. Although there were observed elevations in liver enzymes ALT and ALP and lower creatinine levels in the extract treated groups, no adverse histopathological findings were found. Moringa oleifera dried leaf extract may, therefore, be reasonably safe for consumption. However, the consumption of Moringa oleifera leaves should not exceed a maximum of 70 grams per day to prevent cumulative toxicity of these essential elements over long periods. I. J. Asiedu-Gyekye, S. Frimpong-Manso, C. Awortwe, D. A. Antwi, and A. K. Nyarko Copyright © 2014 I. J. Asiedu-Gyekye et al. All rights reserved. Chlorogenic and Caftaric Acids in Liver Toxicity and Oxidative Stress Induced by Methamphetamine Sun, 20 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/jt/2014/583494/ Methamphetamine intoxication can cause acute hepatic failure. Chlorogenic and caftaric acids are the major dietary polyphenols present in various foods. The aim of this study was to evaluate the protective role of chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine in rats. Thirty-two male albino rats were divided into 4 equal groups. Group 1, which was control group, was injected (i.p) with saline (1 mL/kg) twice a day over seven-day period. Groups 2, 3, and 4 were injected (i.p) with methamphetamine (10 mg/kg) twice a day over seven-day period, where groups 3 and 4 were injected (i.p) with 60 mg/kg chlorogenic acid and 40 mg/kg caftaric acid, respectively, one day before methamphetamine injections. Methamphetamine increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, low-density lipoprotein, and triglycerides. Also, malondialdehyde in serum, liver, and brain and plasma and liver nitric oxide levels were increased while methamphetamine induced a significant decrease in serum total protein, albumin, globulin, albumin/globulin ratio, brain serotonin, norepinephrine and dopamine, blood and liver superoxide dismutase, and glutathione peroxidase levels. Chlorogenic and caftaric acids prior to methamphetamine injections restored all the above parameters to normal values. In conclusion, chlorogenic and caftaric acids before methamphetamine injections prevented liver toxicity and oxidative stress where chlorogenic acid was more effective. Khaled M. M. Koriem and Rowan E. Soliman Copyright © 2014 Khaled M. M. Koriem and Rowan E. Soliman. All rights reserved.