Journal of Toxicology http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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. Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS Thu, 10 Jul 2014 09:57:42 +0000 http://www.hindawi.com/journals/jt/2014/489382/ 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 http://www.hindawi.com/journals/jt/2014/576496/ 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 http://www.hindawi.com/journals/jt/2014/214574/ 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 http://www.hindawi.com/journals/jt/2014/980404/ 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 http://www.hindawi.com/journals/jt/2014/412437/ 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 http://www.hindawi.com/journals/jt/2014/732913/ 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 http://www.hindawi.com/journals/jt/2014/413870/ 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 http://www.hindawi.com/journals/jt/2014/376503/ 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 http://www.hindawi.com/journals/jt/2014/135654/ 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 http://www.hindawi.com/journals/jt/2014/145325/ 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. Influence of Exposure to Benzo[a]pyrene on Mice Testicular Germ Cells during Spermatogenesis Mon, 23 Dec 2013 09:47:11 +0000 http://www.hindawi.com/journals/jt/2013/387850/ The objective of this study was to assess the toxicological effect of exposure to benzo(a)pyrene, B[a]P, on germ cells during spermatogenesis. Mice were exposed to B[a]P at 1, 10, 50, and 100 mg/kg/day for 30 days via oral ingestion. Germ cells, including spermatogonia, spermatocytes, pachytene spermatocytes, and round spermatids, were recovered from testes of mice exposed to B[a]P, while mature spermatozoa were isolated from vas deferens. Reproductive organs were collected and weighed. Apoptotic response of germ cells and mature spermatozoa were qualified using the terminal deoxynucleotidyl transferase mediated deoxy-UTP nick end labeling (TUNEL) assay. B[a]P exposure at ≤10 mg/kg/day for 30 days did not significantly alter concentrations of germ cells and mature spermatozoa and apoptotic response in germ cells and mature spermatozoa. Exposure to B[a]P at 50 and 100 mg/kg/day induced testicular atrophy and yielded a significant reduction in the concentrations of spermatogonia, spermatocytes, pachytene spermatocytes, and round spermatid cells as compared with the control. Also, mature spermatozoa experienced decreased concentrations and viability. B[a]P-exposed mice experienced a significant increase in apoptotic germ cells as compared to the control mice. However, the mice dose concentrations were not relevant for comparison to human exposure. Hueiwang Anna Jeng and Silvina M. Bocca Copyright © 2013 Hueiwang Anna Jeng and Silvina M. Bocca. All rights reserved. Prenatal and Postnatal Polycyclic Aromatic Hydrocarbon Exposure, Airway Hyperreactivity, and Beta-2 Adrenergic Receptor Function in Sensitized Mouse Offspring Thu, 12 Dec 2013 08:44:20 +0000 http://www.hindawi.com/journals/jt/2013/603581/ Despite data associating exposure to traffic-related polycyclic aromatic hydrocarbons (PAH) in asthma, mechanistic support has been limited. We hypothesized that both prenatal and early postnatal exposure to PAH would increase airway hyperreactivity (AHR) and that the resulting AHR may be insensitive to treatment with a β2AR agonist drug, procaterol. Further, we hypothesized that these exposures would be associated with altered β2AR gene expression and DNA methylation in mouse lungs. Mice were exposed prenatally or postnatally to a nebulized PAH mixture versus negative control aerosol 5 days a week. Double knockout β2AR mice were exposed postnatally only. Prenatal exposure to PAH was associated with reduced β2AR gene expression among nonsensitized mice offspring, but not increases in DNA methylation or AHR. Postnatal exposure to PAH was borderline associated with increased AHR among sensitized wildtype, but not knockout mice. In the first study that delivers PAH aerosols to mice in a relatively physiological manner, small effects on AHR and β2AR gene expression, but not β2AR agonist drug activity, were observed. If confirmed, the results may suggest that exposure to PAH, common ambient urban pollutants, affects β2AR function, although the impact on the efficacy of β2AR agonist drugs used in treating asthma remains uncertain. Sophie Chu, Hanjie Zhang, Christina Maher, Jacob D. McDonald, Xiang Zhang, Shuk-Mei Ho, Beizhan Yan, Steven Chillrud, Frederica Perera, Phillip Factor, and Rachel L. Miller Copyright © 2013 Sophie Chu et al. All rights reserved. The Aryl-Hydrocarbon Receptor Protein Interaction Network (AHR-PIN) as Identified by Tandem Affinity Purification (TAP) and Mass Spectrometry Thu, 05 Dec 2013 10:06:40 +0000 http://www.hindawi.com/journals/jt/2013/279829/ The aryl-hydrocarbon receptor (AHR), a ligand activated PAS superfamily transcription factor, mediates most, if not all, of the toxicity induced upon exposure to various dioxins, dibenzofurans, and planar polyhalogenated biphenyls. While AHR-mediated gene regulation plays a central role in the toxic response to dioxin exposure, a comprehensive understanding of AHR biology remains elusive. AHR-mediated signaling starts in the cytoplasm, where the receptor can be found in a complex with the heat shock protein of 90 kDa (Hsp90) and the immunophilin-like protein, aryl-hydrocarbon receptor-interacting protein (AIP). The role these chaperones and other putative interactors of the AHR play in the toxic response is not known. To more comprehensively define the AHR-protein interaction network (AHR-PIN) and identify other potential pathways involved in the toxic response, a proteomic approach was undertaken. Using tandem affinity purification (TAP) and mass spectrometry we have identified several novel protein interactions with the AHR. These interactions physically link the AHR to proteins involved in the immune and cellular stress responses, gene regulation not mediated directly via the traditional AHR:ARNT heterodimer, and mitochondrial function. This new insight into the AHR signaling network identifies possible secondary signaling pathways involved in xenobiotic-induced toxicity. Dorothy M. Tappenden, Hye Jin Hwang, Longlong Yang, Russell S. Thomas, and John J. LaPres Copyright © 2013 Dorothy M. Tappenden et al. All rights reserved. Metabolic Effects of Sucralose on Environmental Bacteria Tue, 03 Dec 2013 10:47:16 +0000 http://www.hindawi.com/journals/jt/2013/372986/ Sucralose was developed as a low cost artificial sweetener that is nonmetabolizable in humans. Sucralose can withstand changes in pH and temperature and is not degraded by the wastewater treatment process. Since the molecule can withstand heat, acidification, and microbial degradation, it is accumulating in the environment and has been found in wastewater, estuaries, rivers, and the Gulf Stream. Environmental isolates were cultured in the presence of sucralose looking for potential sucralose metabolism or growth acceleration responses. Sucralose was found to be nonnutritive and demonstrated bacteriostatic effects on all six isolates. This growth inhibition was directly proportional to the concentration of sucralose exposure, and the amount of the growth inhibition appeared to be species-specific. The bacteriostatic effect may be due to a decrease in sucrose uptake by bacteria exposed to sucralose. We have determined that sucralose inhibits invertase and sucrose permease. These enzymes cannot catalyze hydrolysis or be effective in transmembrane transport of the sugar substitute. Current environmental concentrations should not have much of an effect on environmental bacteria since the bacteriostatic effect seems to be consecration based; however, as sucralose accumulates in the environment, we must consider it a contaminant, especially for microenvironments. Arthur Omran, Gregory Ahearn, Doria Bowers, Janice Swenson, and Charles Coughlin Copyright © 2013 Arthur Omran et al. All rights reserved. Effect of Aqueous Stem Bark Extract of Khaya senegalensis on Some Biochemical, Haematological, and Histopathological Parameters of Rats Mon, 18 Nov 2013 15:40:33 +0000 http://www.hindawi.com/journals/jt/2013/803835/ The subchronic effect of aqueous stem bark extract of Khaya senegalensis on some biochemical, haematological, and histopathological parameters of rats was investigated. The rats were divided into six groups of five rats per group. Groups I to VI were administered graded doses of 0, 400, 800, 1200, 1600, and 2000 mg/kg bw, respectively. The result of study revealed that administration of the Khaya senegalensis for twenty-eight days at the experimental dose resulted in significant () increase in urea, electrolytes (Na+, K+), and creatinine levels. The extract also significantly () increased serum activity of ALT, AST, and ALP. The levels of protein, albumin, and bilirubin were significantly changed when compared to their control values, but they were not dose dependent. The hematological indices assayed in this study were not significantly affected at the experimental dose when compared to the control values. Histological studies of the liver showed cellular degeneration and necrosis and bile duct hyperplasia and fibrosis with lymphocytic infiltration of the hepatocyte, providing supportive evidence for discussing the biochemical findings, indicative of functional derangement. The histological architecture of the kidney and that of the heart were however preserved. The result of this study indicates that the aqueous stem bark extract of K. senegalensis may affect the cellular integrity of vital organs of the body. A. Onu, Y. Saidu, M. J. Ladan, L. S. Bilbis, A. A. Aliero, and S. M. Sahabi Copyright © 2013 A. Onu et al. All rights reserved. Acetaldehyde Content and Oxidative Stress in the Deleterious Effects of Alcohol Drinking on Rat Uterine Horn Sun, 17 Nov 2013 14:57:58 +0000 http://www.hindawi.com/journals/jt/2013/161496/ After alcohol exposure through a standard Lieber and De Carli diet for 28 days, a severe atrophy in the rat uteirne horn was observed, accompanied by significant alterations in its epithelial cells. Microsomal pathway of acetaldehyde production was slightly increased. Hydroxyl radicals were detected in the cytosolic fraction, and this was attributed to participation of xanthine oxidoreductase. They were also observed in the microsomal fraction in the presence of NADPH generating system. No generation of 1-hydroxyethyl was evidenced. The t-butylhydroperoxide-induced chemiluminescence analysis of uterine horn homogenates revealed a significant increase in the chemiluminiscence emission due to ethanol exposure. In the animals repeatedly exposed to alcohol, sulfhydryl content from uterine horn proteins was decreased, but no significant changes were observed in the protein carbonyl content from the same samples. Minor but significant decreasing changes were observed in the GSH content accompanied by a tendency to decrease in the GSH/GSSG ratio. A highly significant finding was the diminished activity content of glutathione peroxidase. Results suggest that acetaldehyde accumulation plus the oxidative stress may play an additional effect to the alcohol-promoted hormonal changes in the uterus reported by others after chronic exposure to alcohol. Lara Romina Buthet, María Eugenia Maciel, Leandro Néstor Quintans, Carmen Rodríguez de Castro, Martín Hernán Costantini, Silvia Laura Fanelli, José Alberto Castro, and Gerardo Daniel Castro Copyright © 2013 Lara Romina Buthet et al. All rights reserved. Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/Siblings Wed, 06 Nov 2013 14:19:49 +0000 http://www.hindawi.com/journals/jt/2013/159810/ It has been postulated that androgen overexposure in a susceptible person leads to excessive brain masculinization and the autism spectrum disorder (ASD) phenotype. In this study, the responses to estradiol (E2), dihydrotestosterone (DHT), and dichlorodiphenyldichloroethylene (DDE) on B-lymphocytes from ASD subjects and controls are compared. B cells were obtained from 11 ASD subjects, their unaffected fraternal twins, and nontwin siblings. Controls were obtained from a different cell bank. Lactate dehydrogenase (LDH) and sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction levels were measured after incubation with different concentrations of E2, DHT, and DDE. XTT/LDH ratio, representative of mitochondria number per cell, was calculated. E2, DHT, and DDE all cause “U”-shaped growth curves, as measured by LDH levels. ASD B cells show less growth depression compared to siblings and controls (). They also have reduced XTT/LDH ratios () when compared to external controls, whereas siblings had values of XTT/LDH between ASD and external controls. B-lymphocytes from people with ASD exhibit a differential response to E2, DHT, and hormone disruptors in regard to cell growth and mitochondrial upregulation when compared to non-ASD siblings and external controls. Specifically, ASD B-lymphocytes show significantly less growth depression and less mitochondrial upregulation when exposed to these effectors. A mitochondrial deficit in ASD individuals is implied. Martyn A. Sharpe, Taylor L. Gist, and David S. Baskin Copyright © 2013 Martyn A. Sharpe et al. All rights reserved. The Benefits and Risks of Consuming Brewed Tea: Beware of Toxic Element Contamination Wed, 23 Oct 2013 18:42:50 +0000 http://www.hindawi.com/journals/jt/2013/370460/ Background. Increasing concern is evident about contamination of foodstuffs and natural health products. Methods. Common off-the-shelf varieties of black, green, white, and oolong teas sold in tea bags were used for analysis in this study. Toxic element testing was performed on 30 different teas by analyzing (i) tea leaves, (ii) tea steeped for 3-4 minutes, and (iii) tea steeped for 15–17 minutes. Results were compared to existing preferred endpoints. Results. All brewed teas contained lead with 73% of teas brewed for 3 minutes and 83% brewed for 15 minutes having lead levels considered unsafe for consumption during pregnancy and lactation. Aluminum levels were above recommended guidelines in 20% of brewed teas. No mercury was found at detectable levels in any brewed tea samples. Teas contained several beneficial elements such as magnesium, calcium, potassium, and phosphorus. Of trace minerals, only manganese levels were found to be excessive in some black teas. Conclusions. Toxic contamination by heavy metals was found in most of the teas sampled. Some tea samples are considered unsafe. There are no existing guidelines for routine testing or reporting of toxicant levels in “naturally” occurring products. Public health warnings or industry regulation might be indicated to protect consumer safety. Gerry Schwalfenberg, Stephen J. Genuis, and Ilia Rodushkin Copyright © 2013 Gerry Schwalfenberg et al. All rights reserved. In Silico Risk Assessment of HLA-A*02:06-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Caused by Cold Medicine Ingredients Sat, 12 Oct 2013 12:43:15 +0000 http://www.hindawi.com/journals/jt/2013/514068/ Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug hypersensitivities with high mortality. Typical over-the-counter drugs of cold medicines are suggested to be causative. As multiple ingredients are generally contained in cold medicines, it is of particular interest to investigate which ingredients are responsible for SJS/TEN. However, experimental examination of causal relationships between SJS/TEN and a particular drug molecule is not straightforward. Significant association between HLA-A*02:06 and SJS/TEN with severe ocular surface complications has been observed in the Japanese. In the present study, we have undertaken in silico docking simulations between various ingredients contained in cold medicines available in Japan and the HLA-A*02:06 molecule. We use the composite risk index (CRI) that is the absolute value of the binding affinity multiplied by the daily dose to assess the potential risk of the adverse reactions. The drugs which have been recognized as causative drugs of SJS/TEN in Japan have revealed relatively high CRI, and the association between SJS/TEN and HLA-A*02:06 has been qualitatively verified. The results have also shown that some drugs whose links to SJS/TEN have not been clinically recognized in Japan show the high CRI and suggested that attention should be paid to their adverse drug reactions. Hideto Isogai, Hiroko Miyadera, Mayumi Ueta, Chie Sotozono, Shigeru Kinoshita, Katsushi Tokunaga, and Noriaki Hirayama Copyright © 2013 Hideto Isogai et al. All rights reserved. The Effects of Eucheuma cottonii on Signaling Pathway Inducing Mucin Synthesis in Rat Lungs Chronically Exposed to Particulate Matter 10 (PM10) Coal Dust Tue, 08 Oct 2013 12:54:22 +0000 http://www.hindawi.com/journals/jt/2013/528146/ This study was aimed at investigating the effects of Eucheuma cottonii (EC) in oxidative stress and the signaling for mucin synthesis in rat lungs chronically exposed to coal dust. Coal dust with concomitant oral administration of ethanolic extract of EC at doses of 150 (EC150) or 300 mg/kg BW (EC300) compared to exposed to PM10 coal dust at doses of 6.25 (CD6.25), 12.5 (CD12.5), or 25 mg/m3 (CD25) (an hour daily for 6 months) and nonexposure group (control). The malondialdehyde (MDA), epidermal growth factor (EGF), transforming growth factor (TGF)-α, epidermal growth factor receptor (EGFR), and MUC5AC levels were determined in the lung. The administration of EC300 significantly (p < 0.05) reduced the MDA levels in groups exposed to all doses of coal dust compared to the respective coal dust-exposed nonsupplemented groups. Although not statistically significant,EC reduced the EGF levels and EGFR expressions in CD12.5 and CD25 groups and decreased the TGF-α, level and MUC5AC expression in CD25 group compared to the respective coal dust-exposed nonsupplemented groups. EC was able to decrease oxidative stress and was also able to decrease signaling for mucin synthesis, at least a part, via reducing the ligand in chronic coal dust exposure. Nia Kania, Elly Mayangsari, Bambang Setiawan, Dian Nugrahenny, Frans Tony, Endang Sri Wahyuni, and M. Aris Widodo Copyright © 2013 Nia Kania et al. All rights reserved. In Vitro Toxicity Evaluation of Engineered Cadmium-Coated Silica Nanoparticles on Human Pulmonary Cells Mon, 30 Sep 2013 09:11:56 +0000 http://www.hindawi.com/journals/jt/2013/931785/ Cytotoxicity of cadmium-containing silica nanoparticles Cd-SiO2NPs (0.05–100 µg/mL) versus SiO2NPs and CdCl2 was evaluated by an in vitro test battery in A549 by assessing (i) mitochondrial function, (ii) membrane integrity/cell morphology, (iii) cell growth/proliferation, (iv) apoptotic pathway, (v) oxidative stress, after short- (24–48 h) and long-term (10 days) exposure. Both Cd-SiO2NPs and CdCl2 produced dose-dependent cytotoxic effects: (i) MTT-assay: similar cytotoxicity pattern was observed at both 24 and 48 h, with a more Cd-SiO2NPs pronounced effect than CdCl2. Cd-SiO2NPs induced mortality (about 50%) at 1 μg/mL, CdCl2 at 25 μg/mL; (ii) calcein-AM/PI staining: decrease in cell viability, noticeable at 25 μg/mL, enhanced markedly at 50 and 100 μg/mL, after 24 h. Cd-SiO2NPs induced higher mortality than CdCl2 (25% versus 4%, resp., at 25 μg/mL) with further exacerbation after 48h; (iii) clonogenic assay: exposure for longer period (10 days) compromised the A549 proliferative capacity at very low dose (0.05 μg/mL); (iv) a progressive activation of caspase-3 immunolabelling was detected already at 1 μg/mL; (v) GSH intracellular level was modified by all compounds. In summary, in vitro data demonstrated that both Cd-SiO2NPs and CdCl2 affected all investigated endpoints, more markedly after Cd-SiO2NPs, while SiO2NPs influenced GSH only. Uliana De Simone, Luigi Manzo, Antonella Profumo, and Teresa Coccini Copyright © 2013 Uliana De Simone et al. All rights reserved.