Journal of Toxicology The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Impact of Exposure to Fenitrothion on Vital Organs in Rats Wed, 16 Nov 2016 14:19:16 +0000 This study was designed to investigate the impact of oral administration of fenitrothion (10 mg/kg) on liver, kidney, brain, and lung function in rats. The effect was studied on days 7, 14, 21, 28, and 42. Our results have shown deterioration in liver function as evidenced by the elevation in serum ALT, AST, ALP, and bilirubin and reduction in albumin and hepatic glycogen. This was associated with a state of hyperglycemia and hyperlipidemia and increased prothrombin time, while hemoglobin content was reduced. In addition, the kidney function was reduced as indicated by the elevation in serum creatinine, uric acid, and BUN, while the serum levels of magnesium, potassium, and sodium were reduced. This study also showed an impairment in brain neurotransmitter (elevated 5-HT, glutamate, GABA, and reduced dopamine and norepinephrine level). This was associated with a reduction in the barrier capacity in brain and lung. Fenitrothion also caused a decrease in cholinesterase activity in serum, lung, and brain activity associated with a state of oxidative stress in all tested organs and hyperammonemia. These results support the hazards of pesticide use and shows the importance of minimizing pesticide use or discovering new safe pesticides. Rasha Abdel-Ghany, Ebaa Mohammed, Shimaa Anis, and Waleed Barakat Copyright © 2016 Rasha Abdel-Ghany et al. All rights reserved. Pattern and Epidemiology of Poisoning in the East African Region: A Literature Review Tue, 01 Nov 2016 09:05:55 +0000 The establishment and strengthening of poisons centres was identified as a regional priority at the first African regional meeting on the Strategic Approach to International Chemicals Management (SAICM) in June 2006. At this meeting, the possibility of a subregional poisons centre, that is, a centre in one country serving multiple countries, was suggested. The WHO Headquarters following consultation with counterparts at the WHO Regional Office for Africa (AFRO) and the SAICM Africa Regional Focal Point successfully submitted a proposal to the SAICM Quick Start Programme (QSP) Trust Fund Committee for a feasibility study into a subregional poisons centre in the Eastern Africa subregion. However, before such a study could be conducted it was deemed necessary to carry out a literature review on the patterns and epidemiology of poisoning in this region so as to inform the feasibility study. The current paper presents the results of this literature review. The literature search was done in the months of June and July 2012 by two independent reviewers with no language or publication date restrictions using defined search terms on PUBMED. After screening, the eventual selection of articles for review and inclusion in this study was done by a third reviewer. Dexter Tagwireyi, Patience Chingombe, Star Khoza, and Mandy Maredza Copyright © 2016 Dexter Tagwireyi et al. All rights reserved. Evaluation of “Dream Herb,” Calea zacatechichi, for Nephrotoxicity Using Human Kidney Proximal Tubule Cells Thu, 15 Sep 2016 09:26:00 +0000 A recent surge in the use of dietary supplements, including herbal remedies, necessitates investigations into their safety profiles. “Dream herb,” Calea zacatechichi, has long been used in traditional folk medicine for a variety of purposes and is currently being marketed in the US for medicinal purposes, including diabetes treatment. Despite the inherent vulnerability of the renal system to xenobiotic toxicity, there is a lack of safety studies on the nephrotoxic potential of this herb. Additionally, the high frequency of diabetes-associated kidney disease makes safety screening of C. zacatechichi for safety especially important. We exposed human proximal tubule HK-2 cells to increasing doses of this herb alongside known toxicant and protectant control compounds to examine potential toxicity effects of C. zacatechichi relative to control compounds. We evaluated both cellular and mitochondrial functional changes related to toxicity of this dietary supplement and found that even at low doses evidence of cellular toxicity was significant. Moreover, these findings correlated with significantly elevated levels of nephrotoxicity biomarkers, lending further support for the need to further scrutinize the safety of this herbal dietary supplement. Miriam E. Mossoba, Thomas J. Flynn, Sanah Vohra, Paddy Wiesenfeld, and Robert L. Sprando Copyright © 2016 Miriam E. Mossoba et al. All rights reserved. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine Mon, 22 Aug 2016 13:29:15 +0000 A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals. Amy Clewell, Gábor Hirka, Róbert Glávits, Philip A. Palmer, John R. Endres, Timothy S. Murbach, Tennille Marx, and Ilona Pasics Szakonyiné Copyright © 2016 Amy Clewell et al. All rights reserved. Macro- and Microelemental Composition and Toxicity of Unsweetened Natural Cocoa Powder in Sprague-Dawley Rats Wed, 17 Aug 2016 12:08:04 +0000 Unsweetened natural cocoa powder (UNCP) is a pulverized high-grade powder of compressed solid blocks which remains after extraction. Little scientific data is available concerning its safety despite the presence of potential toxic elements. Elemental composition in UNCP was analyzed with ED-XRF spectroscopy. Single oral high dose toxicity study was conducted on adult male Sprague-Dawley rats (150 g) by the limit test method. One group received water and the test group 2000 mg/kg UNCP. All animals were observed for 14 days and then euthanized for haematological, biochemical, and histopathological examinations. Thirty-eight (38) elements were found in UNCP. There was an increase in HDL cholesterol (), reduction in LDL cholesterol (), alkaline phosphatase (), and creatinine levels, and slight increase in urea levels (). Haematological changes were not significant. Histopathological analysis showed no toxic effect on the heart, liver, kidney, lungs, testis, and spleen. Intestinal erosion was observed in the test group. UNCP appears to be relatively safe when taken as a single oral high dose of 2000 mg/kg b.w.t. in rats. Caution should however be exercised at high doses due to the high elemental content of copper and high possibility of intestinal lining erosion. Isaac Julius Asiedu-Gyekye, Samuel Frimpong-Manso, Benoit Banga N’guessan, Mahmood Abdulai Seidu, Paul Osei-Prempeh, and Daniel Kwaku Boamah Copyright © 2016 Isaac Julius Asiedu-Gyekye et al. All rights reserved. The Effect of Parathion on Red Blood Cell Acetylcholinesterase in the Wistar Rat Thu, 23 Jun 2016 07:57:41 +0000 Organophosphorus (OP) pesticide poisoning is a significant problem worldwide. Research into new antidotes for these acetylcholinesterase inhibitors, and even optimal doses for current therapies, is hindered by a lack of standardized animal models. In this study, we sought to characterize the effects of the OP pesticide parathion on acetylcholinesterase in a Wistar rat model that included comprehensive medical care. Methods. Male Wistar rats were intubated and mechanically ventilated and then poisoned with between 20 mg/kg and 60 mg/kg of intravenous parathion. Upon developing signs of poisoning, the rats were treated with standard critical care, including atropine, pralidoxime chloride, and midazolam, for up to 48 hours. Acetylcholinesterase activity was determined serially for up to 8 days after poisoning. Results. At all doses of parathion, maximal depression of acetylcholinesterase occurred at 3 hours after poisoning. Acetylcholinesterase recovered to nearly 50% of baseline activity by day 4 in the 20 mg/kg cohort and by day 5 in the 40 and 60 mg/kg cohorts. At day 8, most rats’ acetylcholinesterase had recovered to roughly 70% of baseline. These data should be useful in developing rodent models of acute OP pesticide poisoning. Naofumi Bunya, Keigo Sawamoto, Hanif Benoit, and Steven B. Bird Copyright © 2016 Naofumi Bunya et al. All rights reserved. Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice Wed, 08 Jun 2016 08:23:38 +0000 Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system. Claudia Leticia Moreno Ávila, Jorge H. Limón-Pacheco, Magda Giordano, and Verónica M. Rodríguez Copyright © 2016 Claudia Leticia Moreno Ávila et al. All rights reserved. Tolerability of Capsaicinoids from Capsicum Extract in a Beadlet Form: A Pilot Study Tue, 15 Mar 2016 16:48:39 +0000 A single center, open-label, dose-finding adaptive study was conducted in twelve healthy overweight female subjects. The study was to evaluate the safety and tolerability of the capsaicinoids (CAPs) from Capsicum extract in a beadlet form compared to placebo in a healthy overweight population. The investigational product capsaicinoids (CAPs) from Capsicum extract in a beadlet form (Capsimax®) a proprietary encapsulated form of Capsicum extract in beadlet form supplemented at 2 mg, 4 mg, 6 mg, 8 mg and 10 mg of CAPs. An ascending dose protocol evaluated a total dose of 10 mg daily given in five divided doses (2 mg, 4 mg, 6 mg, 8 mg and 10 mg of CAPs). Each dose was given for a week. Safety and tolerability were assessed. Primary outcomes were tolerability assessments and reports of adverse events. Tolerability assessments were observed on skin color and any changes in skin, bowel movement, digestion, mouth or throat, hair color or changes in hair color, urination includes frequency and burning sensations, breathing, any changes in their health. Secondary outcomes were body weight, body mass index (BMI), blood pressure (SBP/DBP), vital signs, electrocardiograms, clinical chemistry parameters including liver function tests, lung function tests and kidney function tests and complete blood count (CBC). No dose effective changes were observed. The escalating dose levels of CAPs in a beadlet form product found was tolerable and safe for weight management studies. Tolerability assessments and safety blood markers showed no significant changes from baseline. No significant serious adverse events were reported throughout the duration of the study. Further longer term studies are required to explore the tolerability of the product. This trial is registered with ISRCTN: #  ISRCTN10975080. Jayant Deshpande, Shankaranarayanan Jeyakodi, and Vijaya Juturu Copyright © 2016 Jayant Deshpande et al. All rights reserved. Neurotoxic Effect of Benzo[a]pyrene and Its Possible Association with 6-Hydroxydopamine Induced Neurobehavioral Changes during Early Adolescence Period in Rats Mon, 29 Feb 2016 06:54:17 +0000 Exposure to persistent genotoxicants like benzo[a]pyrene (B[a]P) during postnatal days causes neurobehavioral changes in animal models. However, neurotoxic potential of B[a]P and its association with 6-hydroxydopamine (6-OHDA) induced neurobehavioral changes are yet to be explored. The growth of rat brain peaks at the first week of birth and continues up to one month with the attainment of adolescence. Hence, the present study was conducted on male Wistar rats at postnatal day 5 (PND 5) following single intracisternal administration of B[a]P to compare with neurobehavioral and neurotransmitter changes induced by 6-OHDA at PND 30. Spontaneous motor activity was significantly increased by 6-OHDA showing similar trend following B[a]P administration. Total distance travelled in novel open field arena and elevated plus maze was significantly increased following B[a]P and 6-OHDA administration. Neurotransmitter estimation showed significant alleviation of dopamine in striatum following B[a]P and 6-OHDA administration. Histopathological studies of striatum by hematoxylin and eosin (H&E) staining revealed the neurodegenerative potential of B[a]P and 6-OHDA. Our results indicate that B[a]P-induced spontaneous motor hyperactivity in rats showed symptomatic similarities with 6-OHDA. In conclusion, early postnatal exposure to B[a]P in rats causing neurobehavioral changes may lead to serious neurodegenerative consequences during adolescence. Saroj Kumar Das, Bhupesh Patel, and Manorama Patri Copyright © 2016 Saroj Kumar Das et al. All rights reserved. Estimation of the Mechanism of Adrenal Action of Endocrine-Disrupting Compounds Using a Computational Model of Adrenal Steroidogenesis in NCI-H295R Cells Wed, 17 Feb 2016 11:39:26 +0000 Adrenal toxicity is one of the major concerns in drug development. To quantitatively understand the effect of endocrine-active compounds on adrenal steroidogenesis and to assess the human adrenal toxicity of novel pharmaceutical drugs, we developed a mathematical model of steroidogenesis in human adrenocortical carcinoma NCI-H295R cells. The model includes cellular proliferation, intracellular cholesterol translocation, diffusional transport of steroids, and metabolic pathways of adrenal steroidogenesis, which serially involve steroidogenic proteins and enzymes such as StAR, CYP11A1, CYP17A1, HSD3B2, CYP21A2, CYP11B1, CYP11B2, HSD17B3, and CYP19A1. It was reconstructed in an experimental dynamics of cholesterol and 14 steroids from an in vitro steroidogenesis assay using NCI-H295R cells. Results of dynamic sensitivity analysis suggested that HSD3B2 plays the most important role in the metabolic balance of adrenal steroidogenesis. Based on differential metabolic profiling of 12 steroid hormones and 11 adrenal toxic compounds, we could estimate which steroidogenic enzymes were affected in this mathematical model. In terms of adrenal steroidogenic inhibitors, the predicted action sites were approximately matched to reported target enzymes. Thus, our computer-aided system based on systems biological approach may be useful to understand the mechanism of action of endocrine-active compounds and to assess the human adrenal toxicity of novel pharmaceutical drugs. Ryuta Saito, Natsuko Terasaki, Makoto Yamazaki, Naoya Masutomi, Naohisa Tsutsui, and Masahiro Okamoto Copyright © 2016 Ryuta Saito et al. All rights reserved. Modified Rice Straw as Adsorbent Material to Remove Aflatoxin B1 from Aqueous Media and as a Fiber Source in Fino Bread Tue, 16 Feb 2016 16:34:00 +0000 The aims of the current work are in large part the benefit of rice straw to be used as adsorbent material and natural source of fiber in Fino bread. The rice straw was subjected to high temperature for modification process and the chemical composition was carried out and the native rice straw contained about 41.15% cellulose, 20.46% hemicellulose, and 3.91% lignin while modified rice straw has 42.10, 8.65, and 5.81%, respectively. The alkali number was tested and showed an increase in the alkali consumption due to the modification process. The different concentrations of modified rice straw, aflatoxin B1, and pH were tested for removal of aflatoxin B1 from aqueous media and the maximum best removal was at 5% modified rice straw, 5 ng/mL aflatoxin B1, and pH 7. The modified rice straw was added to Fino bread at a level of 5, 10, and 15% and the chemical, rheological, baking quality, staling, and sensory properties were studied. Modified rice straw induced an increase of the shelf life and the produced Fino bread has a better consistency. Sherif R. Mohamed, Tarek A. El-Desouky, Ahmed M. S. Hussein, Sherif S. Mohamed, and Khayria M. Naguib Copyright © 2016 Sherif R. Mohamed et al. All rights reserved. Biomonitoring with Micronuclei Test in Buccal Cells of Female Farmers and Children Exposed to Pesticides of Maneadero Agricultural Valley, Baja California, Mexico Sun, 14 Feb 2016 13:53:29 +0000 Feminization of the agricultural labor is common in Mexico; these women and their families are vulnerable to several health risks including genotoxicity. Previous papers have presented contradictory information with respect to indirect exposure to pesticides and DNA damage. We aimed to evaluate the genotoxic effect in buccal mucosa from female farmers and children, working in the agricultural valley of Maneadero, Baja California. Frequencies of micronucleated cells (MNc) and nuclear abnormalities (NA) in 2000 cells were obtained from the buccal mucosa of the study population (), divided in four groups: (1) farmers (), (2) unexposed (), (3) farmers’ children (), and (4) unexposed children (). We compared frequencies of MNc and NA and fitted generalized linear models to investigate the interaction between these variables and exposition to pesticides. Differences were found between farmers and unexposed women in MNc (), CC (), and PN (). With respect to exposed children, we found higher significant frequencies in MNc (), LN (), CC (), and PN () when compared to unexposed children. Therefore working as a farmer is a risk for genotoxic damage; more importantly indirectly exposed children were found to have genotoxic damage, which is of concern, since it could aid in future disturbances of their health. Idalia Jazmin Castañeda-Yslas, María Evarista Arellano-García, Marco Antonio García-Zarate, Balam Ruíz-Ruíz, María Guadalupe Zavala-Cerna, and Olivia Torres-Bugarín Copyright © 2016 Idalia Jazmin Castañeda-Yslas et al. All rights reserved. Evaluating the Effects of Tetrachloro-1,4-benzoquinone, an Active Metabolite of Pentachlorophenol, on the Growth of Human Breast Cancer Cells Sun, 14 Feb 2016 12:18:49 +0000 Tetrachloro-1,4-benzoquinone (TCBQ), an active metabolite of pentachlorophenol (PCP), is genotoxic and potentially carcinogenic. As an electrophilic and oxidative molecule, TCBQ can conjugate with deoxyguanosine in DNA molecules and/or impose oxidative stress in cells. In the current study, we investigated the effects of TCBQ on intracellular ROS production, apoptosis, and cytotoxicity against three different subtypes of human breast cancer cells. Luminal A subtype MCF7 (ER+, PR+, HER2−) cells maintained the highest intracellular ROS level and were subjected to TCBQ-induced ROS reduction, apoptosis, and cytotoxicity. HER2 subtype Sk-Br-3 (ER−, PR−, HER2+) cells possessed the lowest intracellular ROS level. TCBQ promoted ROS production, inhibited apoptosis, and elevated cytotoxicity (due to necrosis) against Sk-Br-3 cells. Triple-negative/basal-like subtype MDA-MB-231 cells were less sensitive towards TCBQ treatment. Therefore, the effect of prolonged exposure to PCP and its active metabolites on cancer growth is highly cancer-cell-type specific. Binbing Ling, Bosong Gao, and Jian Yang Copyright © 2016 Binbing Ling et al. All rights reserved. Cement Dust Exposure and Perturbations in Some Elements and Lung and Liver Functions of Cement Factory Workers Thu, 11 Feb 2016 09:13:38 +0000 Background. Cement dust inhalation is associated with deleterious health effects. The impact of cement dust exposure on the peak expiratory flow rate (PEFR), liver function, and some serum elements in workers and residents near cement factory were assessed. Methods. Two hundred and ten subjects (50 workers, 60 residents, and 100 controls) aged 18–60 years were studied. PEFR, liver function aspartate and alanine transaminases (AST and ALT) and total and conjugated bilirubin (TB and CB), and serum elements lead (Pb), copper (Cu), manganese (Mn), iron (Fe), cadmium (Cd), selenium (Se), chromium (Cr), zinc (Zn), and arsenic (As) were determined using peak flow meter, colorimetry, and atomic absorption spectrometry, respectively. Data were analysed using ANOVA and correlation at . Results. The ALT, TB, CB, Pb, As, Cd, Cr, Se, Mn, and Cu were significantly higher and PEFR, Fe, and Zn lower in workers and residents compared to controls (). Higher levels of ALT, AST, and Fe and lower levels of Pb, Cd, Cr, Se, Mn, and Cu were seen in cement workers compared to residents (). Negative correlation was observed between duration of exposure and PEFR (, ) in cement workers. Conclusions. Cement dust inhalation may be associated with alterations in serum elements levels and lung and liver functions while long term exposure lowers peak expiratory flow rate. Egbe Edmund Richard, Nsonwu-Anyanwu Augusta Chinyere, Offor Sunday Jeremaiah, Usoro Chinyere Adanna Opara, Etukudo Maise Henrieta, and Egbe Deborah Ifunanya Copyright © 2016 Egbe Edmund Richard et al. All rights reserved. Protective Effect of Vitamins C and E on Depot-Medroxyprogesterone Acetate-Induced Ovarian Oxidative Stress In Vivo Sun, 07 Feb 2016 15:14:01 +0000 A study was designed to investigate ameliorates effect of combined vitamins C and E able to against depot-medroxyprogesterone acetate- (DMPA-) induced ovarian oxidative stress in rat. Twenty-five female Wistar rats were divided into the following groups ( rats each): control (untreated) (C); depot-medroxyprogesterone acetate (DMPA); DMPA plus green vitamin C (at dose of 0.2 mg/gram; 0.4 mg/gram; 0.8 mg/gram) and vitamin E (0.04 IU/gram). The treatment with combined vitamins C and E was performed for four weeks. Analysis of malondialdehyde (MDA) level as a marker of oxidative stress was done colorimetrically. Analysis of SOD level was done by enzyme linked immunosorbent assay (ELISA) technically. This increase in ovarium MDA was significantly () attenuated by medium dose treatments of combined vitamins C and E. DMPA insignificantly decreased SOD levels compared to the untreated group. This decrease in ovarian SOD level was significantly attenuated by all doses of the combined vitamins C and E. In conclusion, DMPA induces ovarian oxidative stress. Combined vitamins C and E prohibit the increase in ovarian lipid peroxidation, at least in part by modulating of superoxide dismutase. Therefore, this may provide an antioxidant therapy for attenuating the ovarian toxicity found in the DMPA therapy. Atik Ismiyati, I. Wayan Arsana Wiyasa, and Dwi Yuni Nur Hidayati Copyright © 2016 Atik Ismiyati et al. All rights reserved. Histopathological Study of Cyclosporine Pulmonary Toxicity in Rats Thu, 28 Jan 2016 15:48:06 +0000 Cyclosporine is considered one of the common worldwide immunosuppressive drugs that are used for allograft rejection prevention. However, articles that address adverse effects of cyclosporine use on the vital organs such as lung are still few. This study aims to investigate pulmonary toxic effect of cyclosporine in rats by assessment of pulmonary histopathological changes using light and electron microscope examination. Sixty male adult albino rats were divided into three groups; each group consists of twenty rats. The first received physiological saline while the second and third groups received 25 and 40 mg/kg/day of cyclosporine, respectively, by gastric gavage for forty-five days. Cyclosporine reduced the lung and body weight with shrinkage or pyknotic nucleus of pneumocyte type II, degeneration of alveoli and interalveolar septum beside microvilli on the alveolar surface, emphysema, inflammatory cellular infiltration, pulmonary blood vessels congestion, and increase of fibrous tissues in the interstitial tissues and around alveoli with negative Periodic Acid-Schiff staining. Prolonged use of cyclosporine induced pulmonary ultrastructural and histopathological changes with the lung and body weight reduction depending on its dose. Said Said Elshama, Ayman El-Meghawry EL-Kenawy, and Hosam-Eldin Hussein Osman Copyright © 2016 Said Said Elshama et al. All rights reserved. Microcystin-LR Induced Immunotoxicity in Mammals Tue, 26 Jan 2016 06:28:45 +0000 Microcystins are toxic molecules produced by cyanobacterial blooms due to water eutrophication. Exposure to microcystins is a global health problem because of its association with various other pathological effects and people all over the world are exposed to microcystins on a regular basis. Evidence shows that microcystin-LR (MC-LR) may adversely affect the immune system, but its specific effects on immune functions are lacking. In the present review, immunotoxicological effects associated with MC-LR in animals, humans, and in vitro models have been reported. Overall, the data shows that chronic exposure to MC-LR has the potential to impair vital immune responses which could lead to increased risk of various diseases including cancers. Studies in animal and in vitro models have provided some pivotal understanding into the potential mechanisms of MC-LR related immunotoxicity suggesting that further investigation, particularly in humans, is required to better understand the relationship between development of disease and the MC-LR exposure. Yaqoob Lone, Mangla Bhide, and Raj Kumar Koiri Copyright © 2016 Yaqoob Lone et al. All rights reserved. Possible Protective Effect of Diacerein on Doxorubicin-Induced Nephrotoxicity in Rats Wed, 20 Jan 2016 13:50:42 +0000 Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Interleukin 1 has major role in DOX-induced nephrotoxicity, so we investigated the effect of interleukin 1 receptor antagonist diacerein (DIA) on DOX-induced nephrotoxicity. DIA (25 and 50 mg/kg/day) was administered orally to rats for 15 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of DOX (15 mg/kg) at the 11th day. We measured levels of serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NOx), catalase, and superoxide dismutase (SOD). In addition, caspase-3, tumor necrosis factor alpha (TNFα), nuclear factor kappa B (NFκB) expressions, and renal histopathology were assessed. Our results showed that DOX-induced nephrotoxicity was ameliorated or reduced by both doses of DIA, but diacerein high dose (DHD) showed more improvement than diacerein low dose (DLD). This protective effect was manifested by significant improvement in all measured parameters compared to DOX treated group by using DHD. DLD showed significant improvement of creatinine, MDA, NOx, GSH, histopathology, and immunohistochemical parameters compared to DOX treated group. Marwa M. M. Refaie, Entesar F. Amin, Nashwa F. El-Tahawy, and Aly M. Abdelrahman Copyright © 2016 Marwa M. M. Refaie et al. All rights reserved. Investigating Therapeutic Potential of Trigonella foenum-graecum L. as Our Defense Mechanism against Several Human Diseases Mon, 18 Jan 2016 16:20:48 +0000 Current lifestyle, stress, and pollution have dramatically enhanced the progression of several diseases in human. Globally, scientists are looking for therapeutic agents that can either cure or delay the onset of diseases. Medicinal plants from time immemorial have been used frequently in therapeutics. Of many such plants, fenugreek is one of the oldest herbs which have been identified as an important medicinal plant by the researchers around the world. It is potentially beneficial in a number of diseases such as diabetes, hypercholesterolemia, and inflammation and probably in several kinds of cancers. It has industrial applications such as synthesis of steroidal hormones. Its medicinal properties and their role in clinical domain can be attributed to its chemical constituents. The 3 major chemical constituents which have been identified as responsible for principle health effects are galactomannan, 4-OH isoleucine, and steroidal saponin. Numerous experiments have been carried out in vivo and in vitro for beneficial effects of both the crude chemical and of its active constituent. Due to its role in health care, the functional food industry has referred to it as a potential nutraceutical. This paper is about various medicinal benefits of fenugreek and its potential application as therapeutic agent against several diseases. Shivangi Goyal, Nidhi Gupta, and Sreemoyee Chatterjee Copyright © 2016 Shivangi Goyal et al. All rights reserved. Chalcone Scaffold in Anticancer Armamentarium: A Molecular Insight Sun, 03 Jan 2016 09:50:42 +0000 Cancer is an inevitable matter of concern in the medicinal chemistry era. Chalcone is the well exploited scaffold in the anticancer domain. The molecular mechanism of chalcone at cellular level was explored in past decades. This mini review provides the most recent updates on anticancer potential of chalcones. Manik Das and Kuntal Manna Copyright © 2016 Manik Das and Kuntal Manna. All rights reserved. Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis Thu, 31 Dec 2015 06:00:18 +0000 Doxorubicin (DOX) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days) and sitagliptin (10 mg/kg dissolved in DW p.o. for seven days) in a model of DOX-induced (single dose 15 mg/kg i.p. at the fifth day) cardiotoxicity in rats. Results of our study revealed that pretreatment with metformin or sitagliptin produced significant () cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group. These results may suggest using metformin and/or sitagliptin as preferable drugs for diabetic patients suffering from cancer and receiving DOX in their chemotherapy regimen. Mina Thabet Kelleni, Entesar Farghaly Amin, and Aly Mohamed Abdelrahman Copyright © 2015 Mina Thabet Kelleni et al. All rights reserved. Cytotoxicity, Genotoxicity, and Phytotoxicity of Tannery Effluent Discharged into Palar River Basin, Tamil Nadu, India Tue, 29 Dec 2015 11:12:27 +0000 Ambur, a town located on the banks of Palar River, is considered one of the most polluted areas in India and occupied by hundreds of tanneries and leather product units. The present study was designed to evaluate the toxic effect of discharged tannery effluent (TE) on model agricultural crops, ecofriendly microorganisms, and human blood cells. The phytotoxic effects of TE tested on Allium cepa and Lemna minor revealed inhibition of root growth and significant reduction in number of fronds, protein, and chlorophyll content. Moreover, TE induced chlorosis and tissue necrosis in Nostoc muscorum at low concentration (10%). TE has also negative impact on ecofriendly microorganisms, Bacillus thuringiensis, Rhizobium etli, and Aspergillus terreus which play an important role in the nutrition of plant growth. The genotoxicity of TE was investigated in human leukocytes which showed interference with normal mitotic division with subsequent cell lysis. It also intervened with the normal replication process and induced micronucleus formation in the healthy leukocyte. 5% concentration of TE has been revealed to be toxic to erythrocytes. From this study TE found in the Palar River of Ambur has adverse effects on all the three levels of organisms in ecosystem even at lower concentrations. Suki Roy, Lubbnaz Nagarchi, Ishita Das, Jayasri Mangalam Achuthananthan, and Suthindhiran Krishnamurthy Copyright © 2015 Suki Roy et al. All rights reserved. MeHg Developing Exposure Causes DNA Double-Strand Breaks and Elicits Cell Cycle Arrest in Spinal Cord Cells Thu, 17 Dec 2015 11:35:44 +0000 The neurotoxicity caused by methylmercury (MeHg) is well documented; however, the developmental neurotoxicity in spinal cord is still not fully understood. Here we investigated whether MeHg affects the spinal cord layers development. Chicken embryos at E3 were treated in ovo with 0.1 μg MeHg/50 μL saline solution and analyzed at E10. Thus, we performed immunostaining using anti-γ-H2A.X to recognize DNA double-strand breaks and antiphosphohistone H3, anti-p21, and anti-cyclin E to identify cells in proliferation and cell cycle proteins. Also, to identify neuronal cells, we used anti-NeuN and anti-βIII-tubulin antibodies. After the MeHg treatment, we observed the increase on γ-H2A.X in response to DNA damage. MeHg caused a decrease in the proliferating cells and in the thickness of spinal cord layers. Moreover, we verified that MeHg induced an increase in the number of p21-positive cells but did not change the cyclin E-positive cells. A significantly high number of TUNEL-positive cells indicating DNA fragmentation were observed in MeHg-treated embryos. Regarding the neuronal differentiation, MeHg induced a decrease in NeuN expression and did not change the expression of βIII-tubulin. These results showed that in ovo MeHg exposure alters spinal cord development by disturbing the cell proliferation and death, also interfering in early neuronal differentiation. Fabiana F. Ferreira, Dib Ammar, Gilian F. Bourckhardt, Karoline Kobus-Bianchini, Yara M. R. Müller, and Evelise M. Nazari Copyright © 2015 Fabiana F. Ferreira et al. All rights reserved. Ecological Risk Assessment of Metal Pollution along Greater Cairo Sector of the River Nile, Egypt, Using Nile Tilapia, Oreochromis niloticus, as Bioindicator Wed, 04 Nov 2015 07:18:06 +0000 The present work aims to evaluate seasonal metal pollution along Greater Cairo sector of the River Nile, Egypt, using wild Nile tilapia, Oreochromis niloticus, as bioindicator and to conduct a risk assessment for human consumers. Greater Cairo is the largest populated area along the whole course of River Nile with a wide range of anthropogenic activities. Effects of metal pollution on fish body indices were studied using condition factor (CF) and scaled mass index (SMI). Metal pollution index (MPI) showed that the total metal load in fish organs followed the follwoing order: kidney > liver > gill > muscle which gives a better idea about the target organs for metal accumulation. Metal concentrations in fish muscle (edible tissue) showed the following arrangement: Fe > Zn > Cu > Mn > Pb > Cd. Metal’s bioaccumulation factor (BAF) in fish muscle showed the following arrangement: Zn > Cu > Fe > Mn > Cd and Pb. The hazard index (HI) as an indicator of human health risks associated with fish consumption showed that adverse health effects are not expected to occur in most cases. However, the metals’ cumulative risk effects gave an alarming sign specifically at high fish consumption rates. Wael A. Omar, Wafai Z. A. Mikhail, Hanaa M. Abdo, Tarek A. Abou El Defan, and Mamdouh M. Poraas Copyright © 2015 Wael A. Omar et al. All rights reserved. Acute β-N-Methylamino-L-alanine Toxicity in a Mouse Model Thu, 29 Oct 2015 12:23:28 +0000 The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) is considered to be an “excitotoxin,” and its suggested mechanism of action is killing neurons. Long-term exposure to L-BMAA is believed to lead to neurodegenerative diseases including Parkinson’s and Alzheimer’s diseases and amyotrophic lateral sclerosis (Lou Gehrig’s disease). Objectives of this study were to determine the presumptive median lethal dose (LD50), the Lowest-Observed-Adverse-Effect Level (LOAEL), and histopathologic lesions caused by the naturally occurring BMAA isomer, L-BMAA, in mice. Seventy NIH Swiss Outbred mice (35 male and 35 female) were used. Treatment group mice were injected intraperitoneally with 0.03, 0.3, 1, 2, and 3 mg/g body weight L-BMAA, respectively, and control mice were sham-injected. The presumptive LD50 of L-BMAA was 3 mg/g BW and the LOAEL was 2 mg/g BW. There were no histopathologic lesions in brain, liver, heart, kidney, lung, or spleen in any of the mice during the 14-day study. L-BMAA was detected in brains and livers in all of treated mice but not in control mice. Males injected with 0.03 mg/g BW, 0.3 mg/g BW, and 3.0 mg/g BW L-BMAA showed consistently higher concentrations (P < 0.01) in brain and liver samples as compared to females in those respective groups. Maitham Ahmed Al-Sammak, Douglas G. Rogers, and Kyle D. Hoagland Copyright © 2015 Maitham Ahmed Al-Sammak et al. All rights reserved. The Protective Effects of Nigella sativa and Its Constituents on Induced Neurotoxicity Thu, 29 Oct 2015 07:34:56 +0000 Nigella sativa (N. sativa) is an annual plant and widely used as medicinal plant throughout the world. The seeds of the plant have been used traditionally in various disorders and as a spice to ranges of Persian foods. N. sativa has therapeutic effects on tracheal responsiveness (TR) and lung inflammation on induced toxicity by Sulfur mustard. N. sativa has been widely used in treatment of various nervous system disorders such as Alzheimer disease, epilepsy, and neurotoxicity. Most of the therapeutic properties of this plant are due to the presence of some phenolic compounds especially thymoquinone (TQ), which is major bioactive component of the essential oil. The present review is an effort to provide a comprehensive study of the literature on scientific researches of pharmacological activities of the seeds of this plant on induced neurotoxicity. Mohammad Reza Khazdair Copyright © 2015 Mohammad Reza Khazdair. All rights reserved. Evaluation of Possible Genotoxic Activity of Dirithromycin in Cultured Human Lymphocytes Wed, 21 Oct 2015 11:20:51 +0000 Dirithromycin antibiotic is a 14-membered lactone ring macrolide and is widely used in medicine to treat many different types of bacterial infections. In the present study, the possible genotoxicity of dirithromycin was evaluated in cultured human lymphocytes by using sister chromatid exchanges (SCEs), chromosome aberration (CA), and micronucleus (MN) tests and also cell proliferation kinetics such as mitotic index (MI), replication index (RI), and nuclear division index (NDI) were analyzed for cytotoxicity. Cell cultures were treated with four different concentrations of dirithromycin (37.75, 67.50, 125, and 250 µg/mL) for 24 and 48 h periods. Dirithromycin significantly induced SCE and MN frequency at all concentrations in both 24 and 48 h treated cells. In addition, CA level has been markedly increased in the cells treated with almost all concentrations of dirithromycin for 24 (except 37.75 µg/mL) and 48 h treatment periods as compared to control. However, MI, RI, and NDI values were not affected by the dirithromycin treatment (p > 0.05). The results of this study indicated that dirithromycin treatment caused genetic damage by increasing the level of cytogenetic endpoints, suggesting its genotoxic and mutagenic action on human lymphocytes in vitro. Ahmet Kayraldız, Lale Dönbak, Ayşe Yavuz Kocaman, Esra Köker, and Şule Gökçe Copyright © 2015 Ahmet Kayraldız et al. All rights reserved. Alteration of Blood Parameters and Histoarchitecture of Liver and Kidney of Silver Barb after Chronic Exposure to Quinalphos Thu, 08 Oct 2015 09:46:57 +0000 Quinalphos (QP) is commonly used for pest control in the agricultural fields surrounding freshwater reservoirs. This study was conducted to evaluate the chronic toxicity of this pesticide on blood parameters and some organs of silver barb, Barbonymus gonionotus. Fish were exposed to two sublethal concentrations, 0.47 ppm and 0.94 ppm, of QP for a period of 28 days. All the blood parameters (red blood cell, hematocrit, and hemoglobin) and blood glucose except for white blood cells decreased with increasing concentration of toxicant and become significantly lower () at higher concentration when compared with control. The derived hematological indices of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were equally altered compared to control. Histoarchitectural changes of liver and kidney were observed after exposure to the QP. Hypertrophy of hepatocytes, mild to severe necrosis, ruptured central vein, and vacuolation were observed in the liver of treated groups. Highly degenerated kidney tubules and hematopoietic tissue, degeneration of renal corpuscle, vacuolization, and necrosis were evident in the kidney of treated groups. In conclusion, chronic exposure to QP at sublethal concentrations induced hematological and histological alterations in silver barb and offers a simple tool to evaluate toxicity derived alterations. Golam Mohammod Mostakim, Md. Mahiuddin Zahangir, Mahbuba Monir Mishu, Md. Khalilur Rahman, and M. Sadiqul Islam Copyright © 2015 Golam Mohammod Mostakim et al. All rights reserved. Chromium Exposure and Hygienic Behaviors in Printing Workers in Southern Thailand Sun, 13 Sep 2015 12:20:56 +0000 Objectives. The main objective of this study was to assess the chromium exposure levels in printing workers. The study evaluated the airborne, serum, and urinary chromium levels and determines any correlation between level of chromium in specimen and airborne chromium levels. Material and Methods. A cross-sectional study was conducted with 75 exposed and 75 matched nonexposed subjects. Air breathing zone was measured by furnace atomic absorption spectrophotometer. Serum and urine samples were collected to determine chromium levels by graphite furnaces atomic absorption spectrometer chromium analyzer. Results and Discussion. The printing workers’ urinary chromium levels ( μg/g creatinine) and serum chromium levels ( μg/L) were significantly higher than the control group ( and ). Work position, duration of work, personal protective equipment (PPE), and personal hygiene were significantly associated with urinary chromium level and serum chromium levels ( and ). This study found a correlation between airborne chromium levels and urinary chromium levels (, ). A multiple regression model was constructed. Significant predictors of urinary and serum chromium levels were shown in this study. Conclusion. Improvements in working conditions, occupational health training, and PPE use are recommended to reduce chromium exposure. Somsiri Decharat Copyright © 2015 Somsiri Decharat. All rights reserved. Neuroprotective Effects of Alpha-Mangostin on MPP+-Induced Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells Tue, 18 Aug 2015 09:48:17 +0000 In vitro studies have shown that extracts from mangosteen (Garcinia mangostana Linn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson’s disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP+-induced apoptosis. The effects of alpha-mangostin on MPP+-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real-time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP+ on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP+. Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha-mangostin and MPP+. The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP+ treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP+-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation. Prachya Janhom and Permphan Dharmasaroja Copyright © 2015 Prachya Janhom and Permphan Dharmasaroja. All rights reserved.