Journal of Toxicology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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. Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS Thu, 10 Jul 2014 09:57:42 +0000 Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p.) for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production. Mohamed A. Morsy, Salwa A. Ibrahim, Entesar F. Amin, Maha Y. Kamel, Rehab A. Rifaai, and Magdy K. Hassan Copyright © 2014 Mohamed A. Morsy et al. All rights reserved. Analysis and Determination of Trace Metals (Nickel, Cadmium, Chromium, and Lead) in Tissues of Pampus argenteus and Platycephalus indicus in the Hara Reserve, Iran Thu, 10 Jul 2014 07:03:16 +0000 The accumulations of Cd, Ni, Pb, and Cr were measured in muscle, gill, kidney, and liver of Platycephalus indicus and Pampus argenteus. Our results indicated that all metals were found to be the highest in tissues in P. indicus (benthic species). Except Ni in P. indicus, concentrations of metals and bioaccumulation factor were in the following sequence: liver > kidney > gill > muscle. The data revealed that there is a significant negative correlation between concentrations of metals and size and age factors. The Ni and Cr levels in the muscles were higher than the maximum acceptable limit recommended by WHO and FEPA. Similarly, the concentration of Pb measured in P. indicus muscle exceeded the FAO standard limit. Sahar Mohammadnabizadeh, Alireza Pourkhabbaz, and Reza Afshari Copyright © 2014 Sahar Mohammadnabizadeh et al. All rights reserved. Acute Methotrexate Ingestions in Adults: A Report of Serious Clinical Effects and Treatments Wed, 16 Apr 2014 07:01:33 +0000 Objective. Limited reported data have reports effects after acute ingestion of methotrexate. Treatment recommendations do not differentiate between exposure routes. Our objective was to determine the frequency of significant toxicity effects and use of therapy after methotrexate ingestion in adults. Methods. We performed a retrospective study on adult cases reported to 6 poison centers over 6 years (2000–2005) which exceed 180,000 exposures/year. Variables collected included demographics, dosages ingested, coingestions, clinical effects, and therapies with outcomes. Results. Sixty-three patients examined over the 6-year period met inclusion criteria. No patient in the series received dialysis or died. The mean dose ingested for all patients was 24 mg (range 2.5–100 mg) and the mean dose for suicidal ingestions was 47.5 mg (12.5–100 mg). The most common clinical effects were abdominal pain, oral irritation, throat irritation, nausea, dizziness, and headache. Nine patients received folinic acid and 3 patients received sodium bicarbonate. No patient developed renal failure, bone marrow suppression, seizure, or coma. No patient died or received dialysis. Conclusion. In our series of patients from 6 poison centers over six years, 63 cases of acute adult methotrexate ingestions were reported. Methotrexate toxicity from ingestion in adults was uncommon and rarely toxic. Vikhyat S. Bebarta, Matthew D. Hensley, and Douglas J. Borys Copyright © 2014 Vikhyat S. Bebarta et al. All rights reserved. Safety Evaluation of Artocarpus altilis as Pharmaceutical Agent in Wistar Rats Wed, 02 Apr 2014 11:58:40 +0000 This study was designed to elucidate the acute toxicity of Artocarpus altilis leaf and bark extracts. In acute toxicity study, no mortality or any toxic reaction was recorded in any group after 14 days of administering the extracts (2000 mg Kg−1 BW). The extracts (ALA, ABA, ALM, and ABM) did not cause any behavioural or physical changes in experimental rats. There was no significant () difference in the biochemical parameters analysed between the groups. Slight elevation in activities of AST and ALT in extract treated groups was observed, but this did not exert any deleterious effect on the normal metabolism which was supported by the histopathology of liver. Histopathological studies showed no remarkable changes after 14 days of oral administration of ALA, ABA, ALM, and ABM extracts. The study contributes to establishing the nontoxic quality parameters of Artocarpus altilis leaf and bark parts and the results suggest the safety of the extracts in therapeutic uses. Sudha Sairam and Asna Urooj Copyright © 2014 Sudha Sairam and Asna Urooj. All rights reserved. Acute Toxicity and Determination of the Active Constituents of Aqueous Extract of Uncaria tomentosa Bark in Hyphessobrycon eques Thu, 06 Mar 2014 08:23:13 +0000 Uncaria tomentosa is a medicinal plant used in folk medicine by Amazon tribes. In this study the constituents of aqueous extract of U. tomentosa bark were quantified by chromatographic technique and its lethal concentration 50 (48 h) in Hyphessobrycon eques was determined. The chromatography showed high levels of oxindole alkaloids, quinovic acid glycosides, and low molecular weight polyphenols. The CL50 48 h was 1816 mg/L. Fish showed behavior changes at concentrations above 2000 mg/L, accompanied by a significant decrease of dissolved oxygen. At the highest concentration 100% mortality was observed attributed to oxygen reduction by the amount of oxindole alkaloids, polyphenols accumulation of the extract in the gills, and the interaction of these compounds with dopamine. In conclusion, the aqueous extract of U. tomentosa did not alter the chemical components and it was shown that U. tomentosa has low toxicity to H. eques; therefore, it can be used safely in this species. Jefferson Yunis Aguinaga, Gustavo S. Claudiano, Paulo F. Marcusso, Cynthia Ikefuti, George G. Ortega, Silas F. Eto, Claudinei da Cruz, Juliet R. E. Moraes, Flávio R. Moraes, and João B. K. Fernandes Copyright © 2014 Jefferson Yunis Aguinaga et al. All rights reserved. Botulinum Toxin Suppression of CNS Network Activity In Vitro Wed, 12 Feb 2014 13:56:39 +0000 The botulinum toxins are potent agents which disrupt synaptic transmission. While the standard method for BoNT detection and quantification is based on the mouse lethality assay, we have examined whether alterations in cultured neuronal network activity can be used to detect the functional effects of BoNT. Murine spinal cord and frontal cortex networks cultured on substrate integrated microelectrode arrays allowed monitoring of spontaneous spike and burst activity with exposure to BoNT serotype A (BoNT-A). Exposure to BoNT-A inhibited spike activity in cultured neuronal networks where, after a delay due to toxin internalization, the rate of activity loss depended on toxin concentration. Over a 30 hr exposure to BoNT-A, the minimum concentration detected was 2 ng/mL, a level consistent with mouse lethality studies. A small proportion of spinal cord networks, but not frontal cortex networks, showed a transient increase in spike and burst activity with exposure to BoNT-A, an effect likely due to preferential inhibition of inhibitory synapses expressed in this tissue. Lastly, prior exposure to human-derived antisera containing neutralizing antibodies prevented BoNT-A induced inhibition of network spike activity. These observations suggest that the extracellular recording from cultured neuronal networks can be used to detect and quantify functional BoNT effects. Joseph J. Pancrazio, Kamakshi Gopal, Edward W. Keefer, and Guenter W. Gross Copyright © 2014 Joseph J. Pancrazio et al. All rights reserved. Concentration of Cd, Pb, Hg, and Se in Different Parts of Human Breast Cancer Tissues Tue, 11 Feb 2014 00:00:00 +0000 Breast cancer is the major cause of cancer morbidity and mortality between women in the world. Metals involved in environmental toxicology are closely related to tumor growth and cancer. On the other hand, some metals such as selenium have anticarcinogenic properties. The aim of this study is to determine the concentration of cadmium, lead, mercury, and selenium in separated parts of tegmen, tumor, tumor adiposity, and tegmen adiposity of 14 breast cancer tissues which have been analyzed by graphite furnace atomic absorption (AA-670) and ICP-OES (ULTIMA 2CE). Our results show that Se and Hg have maximum and minimum concentration, respectively. Statistical analysis reveals no significant differences between metal accumulations in different parts of cancer tissues and this observation might be due to the close relation of separated parts of fatty breast organ. Thus, we could conclude that a high level of these heavy metals is accumulated in Iranian cancerous breasts and their presence can be one of the reasons of cancer appearance. Mehrnoosh Mohammadi, Alireza Riyahi Bakhtiari, and Saber Khodabandeh Copyright © 2014 Mehrnoosh Mohammadi et al. All rights reserved. Sanitary Risks Connected to the Consumption of Infusion from Senna rotundifolia L. Contaminated with Lead and Cadmium in Cotonou (Benin) Wed, 29 Jan 2014 11:33:57 +0000 This study carried out an assessment of sanitary risks connected to the consumption of Senna rotundifolia Linn. contaminated with lead and cadmium. This plant was collected and analyzed by atomic absorption spectrophotometry. The results revealed a contamination of plants from markets of Dantokpa, Vossa, and Godomey with heavy metals. Senna from Vossa was higher in cadmium and lead levels (Pb: 2.733 mg/kg ± 0.356 mg/kg; Cd: 0.58 mg/kg ± 0.044 mg/kg) compared to the two other places (Pb: 1.825 mg/kg ± 0.133 mg/kg, Cd: 0.062 mg/kg ± 0.015 mg/kg and Pb: 1.902 mg/kg ± 0.265 mg/kg, Cd: 0.328 mg/kg ± 0.024 mg/kg), respectively, for Dantokpa and Godomey. In terms of risk assessment through the consumption of Senna, the values recorded for lead were nine times higher with children and six times higher with adults than the daily permissive intake (Pb: 3.376 × 10−2 mg/kg/day for children and 2.105 × 10−2 mg/kg/day for adults versus 3.6 × 10−3 mg/kg/day for DPI). With respect to cadmium, there was no significant difference between the recorded values and the DPI (Cd: 1 × 14 10−3 mg/ kg/day for children and Cd: 0.71 × 10−3 mg/ kg/day for adults versus Cd: 1 × 10−3 mg/kg/day for adults). This exposure of the population to lead and cadmium through the consumption of antimalarial healing plants could pose public health problems. S. A. Montcho, K. Koudouvo, A. P. E. Yehouenou, P. Guedenon, L. Koumolou, M. Oke Sopoh, V. Dougnon, Mensavi F. Gbéassor, E. E. Creppy, M. Boko, and A. P. Edorh Copyright © 2014 S. A. Montcho et al. All rights reserved. Toxicological Study of Ocimum sanctum Linn Leaves: Hematological, Biochemical, and Histopathological Studies Wed, 29 Jan 2014 00:00:00 +0000 The present study was aimed to study the acute and subacute toxicity studies with orally administered 50% ethanolic leaves extract of Ocimum sanctum Linn (OSE). In acute toxicity tests, four groups of mice were orally treated with doses of 200, 600, and 2000 mg/kg, and general behavior, adverse effects, and mortality were recorded for up to 14 days. In subacute toxicity study, rats received OSE by gavage at the doses of 200, 400, and 800 mg/kg/day for 28 days, and biochemical, hematological, and histopathological changes in tissues (liver, kidney, spleen, heart, and testis/ovary) were determined. OSE did not produce any hazardous symptoms or death and CNS and ANS toxicities in the acute toxicity test. Subacute treatment with OSE did not show any change in body weight, food and water consumption, and hematological and biochemical profiles. In addition, no change was observed both in macroscopic and microscopic aspects of vital organs in rats. Our result showed that Ocimum sanctum extract could be safe for human use. M. K. Gautam and R. K. Goel Copyright © 2014 M. K. Gautam and R. K. Goel. All rights reserved. Cyclosporine and Herbal Supplement Interactions Sun, 12 Jan 2014 00:00:00 +0000 Cyclosporine (CyA) is a well-known immunosuppressant with a narrow therapeutic window. Its bioavailability is affected by many other traditional drugs and herbal extracts. Cytochrome P-450 isoenzymes CYP3A4 and CYP3A5 and protein P-glycoprotein (P-gp) are involved in CyA bioavailability. Interactions of CyA with herbal extracts are not well known, but, given their increased concomitant use, it is important to know which extracts, many of which are commonly self-prescribed, can affect CyA blood concentrations. Decreased CyA blood concentration has been shown with St John’s wort in case reports and, in vivo animal studies, with ginger, liquorice, scutellariae radix, and quercetin. Increased CyA concentration has been reported in patients with grapefruit juice, chamomile, or berberine, and with cannabidiol or resveratrol in animal studies. Effects of Echinacea and Serenoa repens on CyA levels have not been shown consistently, but concomitant use should be avoided. Although findings from animal studies cannot be directly translated into humans, avoiding concomitant use of herbal extracts is prudent until human clinical studies have ruled out any possible interaction. Clinicians should interview their patients carefully about their use of herbal supplements before CyA administration, and those receiving CyA should be warned about possible interactions between herbal preparations and CyA. D. Colombo, L. Lunardon, and G. Bellia Copyright © 2014 D. Colombo et al. All rights reserved.