Journal of Toxicology The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Hepatocyte CYP2B6 Can Be Expressed in Cell Culture Systems by Exerting Physiological Levels of Shear: Implications for ADME Testing Sun, 10 Sep 2017 08:48:22 +0000 Cytochrome 2B6 (CYP2B6) has substantial clinical effects on morbidity and mortality and its effects on drug metabolism should be part of hepatotoxicity screening. Examples of CYP2B6’s impacts include its linkage to mortality during cyclophosphamide therapy and its role in determining hepatotoxicity and CNS toxicity during efavirenz therapy for HIV infection. CYP2B6 is key to metabolism of many common drugs from opioids to antidepressants, anesthetics, and anticonvulsants. But CYP2B6 has been extremely difficult to express in cell culture, and as a result, it has been largely deemphasized in preclinical toxicity studies. It has now been shown that CYP2B6 expression can be supported for extended periods of time using suspension culture techniques that exert physiological levels of shear. New understanding of CYP2B6 has identified five clinically significant genetic polymorphisms that have a high incidence in many populations and that convey a substantial dynamic range of activity. We propose that, with the use of culture devices exerting physiological shear levels, CYP2B6 dependent drug testing, including definition of polymorphisms and application of specific inhibitors, should be a standard part of preclinical absorption, distribution, metabolism, and excretion (ADME) testing. Timothy G. Hammond and Holly H. Birdsall Copyright © 2017 Timothy G. Hammond and Holly H. Birdsall. All rights reserved. Optimization of Aflatoxin B1 Aptasensing Sun, 14 May 2017 07:16:35 +0000 Combination of aptamers with DNAzymes attracted intense attention for development of DNA-based biosensors for detection of mycotoxins. In the present study a combination of aflatoxin B1 specific aptamer and HRP- (horseradish peroxidase-) mimicking DNAzyme was optimized for detecting aflatoxin B1. Detecting approach is based on the binding affinity of aflatoxin B1 to its specific aptamer and conversion of substrate to a detectable colorimetric signal by a linked DNAzyme. Compared to conventional methods for aflatoxin B1 detection, DNA-based assay has the advantages of low cost, long-term stability, and rapid, simple, and user-friendly steps. Marzieh Jafari, Mohsen Rezaei, Heibatullah Kalantari, Maryam Tabarzad, and Bahram Daraei Copyright © 2017 Marzieh Jafari et al. All rights reserved. Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat Tue, 28 Mar 2017 00:00:00 +0000 Turoctocog alfa pegol (N8-GP) is a glycoPEGylated human recombinant factor VIII for the treatment of hemophilia A. The safety profile of rFVIII, and polyethylene glycols (PEG) technology, is well-established. Conducting long-term toxicity studies in animals using human proteins can be complicated by anti-drug antibody (ADA) development. To evaluate long-term safety of N8-GP, 26- and 52-week toxicity studies were conducted in immune-deficient rats dosed intravenously every fourth day with 0, 50, 150, 500, or 1200 IU/kg N8-GP. Observations included clinical observations, body weight, ophthalmoscopy, hematology, chemistry, coagulation, urinalysis, toxicokinetics, antibody analysis, and macroscopic/microscopic organ examination. Immunohistochemical staining examined the distribution of PEG in the brain. No adverse test item-related findings were seen and PEG was not detected in the brain. Exposure was confirmed for ~75% of the animals dosed with 500 and 1200 IU/kg N8-GP; the high lower limit of quantification of the bioanalysis assay prevented confirmation of exposure in the lower doses. A small number of animals developed ADAs, and the proportion of animals surviving until scheduled termination was >80%. N8-GP was well tolerated, and the immune-deficient rat proved suitable for testing long-term toxicity of human proteins that are immunogenic in animals. Caroline E. Rasmussen, Jette Nowak, Julie M. Larsen, Emma Moore, David Bell, Kai Chiu Liu, Nanna Skall Sorensen, Wendela A. Kappers, Thomas Krogh-Meibom, and Hanne Offenberg Copyright © 2017 Caroline E. Rasmussen et al. All rights reserved. Cytotoxic and Genotoxic Effects of Acephate on Human Sperm Tue, 14 Mar 2017 09:37:26 +0000 Extensive use of organophosphorus pesticides (OPs) could alter semen quality and sperm DNA at different stages of spermatogenesis. Acephate is a highly toxic extensively used OP and, therefore, we aimed to evaluate the effects of acephate on human semen quality and sperm DNA integrity. Sperm collected from healthy males were exposed to 0, 50, 100, and 200 μg/mL of acephate and incubated for 1 h, 2 h, and 3 h. Subsequently, sperm motility, vitality, functional integrity of plasma membrane, sperm capacitation, and DNA damage were examined. Result showed a significant decline of the motility at 100 μg/mL after 3 h and with 200 μg/mL after 1 h, 2 h, and 3 h. Viability was significantly reduced at 200 μg/mL after 2 h and 3 h. Functional integrity was significantly affected at 100 μg/mL after 3h and in 200 μg/mL dose after 2 h and 3h. Similarly, sperm capacitation was significantly affected at 200 μg/mL after 1 h, 2 h, and 3 h and at 100 μg/mL at 3 h. DNA damage was significantly increased only in 200 μg/mL dose after 3 h. The study suggests that exposure to acephate may result in alterations of sperm structure and function thus contributing towards deteriorating in human semen quality triggering infertility. M. A. Thamali Dhanushka and L. Dinithi. C. Peiris Copyright © 2017 M. A. Thamali Dhanushka and L. Dinithi. C. Peiris. All rights reserved. Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats Sun, 05 Feb 2017 10:34:42 +0000 Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels () and AST levels () than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment (). The liver enzyme levels suggested that ketoconazole had the highest risk in causing liver injury followed by itraconazole, fluconazole, terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination. Star Khoza, Ishmael Moyo, and Denver Ncube Copyright © 2017 Star Khoza et al. All rights reserved. Distribution of Heavy Metals in Surface Sediments of the Bay of Bengal Coast Tue, 31 Jan 2017 09:21:35 +0000 The concentrations of major (Si, Al, Ca, Fe, and K) and minor (Cd, Mn, Ni, Pb, U, Zn, Co, Cr, As, Cu, Rb, Sr, and Zr,) elements in the surficial sediments were studied in an attempt to establish their concentration in the Bengal coast. It was revealed that the majority of the trace elements have been introduced into the Bengal marine from the riverine inflows that are also affected by the impact of industrial, ship breaking yard, gas production plant, and urban wastes. The concentration of heavy metals was measured using Atomic Absorption Spectroscopy and Energy Dispersive X-ray fluorescence instruments. The highest concentrations for several trace elements were thus recorded which generally decrease with distance from the coast. It was observed that the heavy metal concentrations in the sediments generally met the criteria of international marine sediment quality. However, both the contamination factor and pollution load index values suggested the elevation of some metals’ concentrations in the region. Constant monitoring of the Bengal coast water quality needs to be recorded with a view to minimizing the risk of health of the population and the detrimental impacts on the aquatic ecosystem. M. Z. H. Khan, M. R. Hasan, M. Khan, S. Aktar, and K. Fatema Copyright © 2017 M. Z. H. Khan et al. All rights reserved. Cisplatin-Associated Ototoxicity: A Review for the Health Professional Tue, 27 Dec 2016 14:44:05 +0000 Cisplatin is an effective drug used in the treatment of many cancers, yet its ototoxic potential places cancer patients, exposed to this drug, at risk of hearing loss, thus negatively impacting further on a patient’s quality of life. It is paramount for health care practitioners managing such patients to be aware of cisplatin’s ototoxic properties and the clinical signs to identify patients at risk of developing hearing loss. English peer-reviewed articles from January 1975 to July 2015 were assessed from PubMed, Science Direct, and Ebscohost. Seventy-nine articles and two books were identified for this review, using MeSH terms and keywords such as “ototoxicity”, “cisplatin”, “hearing loss”, and “ototoxicity monitoring”. This review provides an up-to-date overview of cisplatin-associated ototoxicity, namely, its clinical features, incidence rates, and molecular and cellular mechanisms and risk factors, to health care practitioners managing the patient with cancer, and highlights the need for a team-based approach to complement an audiological monitoring programme to mitigate any further loss in the quality of life of affected patients, as there is currently no otoprotective agent recommended routinely for the prevention of cisplatin-associated ototoxicity. It also sets the platform for effective dialogue towards policy formulation and strengthening of health systems in developing countries. Jessica Paken, Cyril D. Govender, Mershen Pillay, and Vikash Sewram Copyright © 2016 Jessica Paken et al. All rights reserved. Role of Bioadsorbents in Reducing Toxic Metals Mon, 19 Dec 2016 13:03:48 +0000 Industrialization and urbanization have led to the release of increasing amounts of heavy metals into the environment. Metal ion contamination of drinking water and waste water is a serious ongoing problem especially with high toxic metals such as lead and cadmium and less toxic metals such as copper and zinc. Several biological materials have attracted many researchers and scientists as they offer both cheap and effective removal of heavy metals from waste water. Therefore it is urgent to study and explore all possible sources of agrobased inexpensive adsorbents for their feasibility in the removal of heavy metals. The objective was to study inexpensive adsorbents like various agricultural wastes such as sugarcane bagasse, rice husk, oil palm shell, coconut shell, and coconut husk in eliminating heavy metals from waste water and their utilization possibilities based on our research and literature survey. It also shows the significance of developing and evaluating new potential biosorbents in the near future with higher adsorption capacity and greater reusable options. Blessy Baby Mathew, Monisha Jaishankar, Vinai George Biju, and Krishnamurthy Nideghatta Beeregowda Copyright © 2016 Blessy Baby Mathew et al. All rights reserved. Comparisons of Curative Effects of Chlorophyll from Sauropus androgynus (L) Merr Leaf Extract and Cu-Chlorophyllin on Sodium Nitrate-Induced Oxidative Stress in Rats Thu, 08 Dec 2016 06:54:03 +0000 Sodium nitrate (NaNO2) widely used as food additive for coloring and preserving meat has been reported to induce oxidative stress and cause histopathologic changes, nitrosative tissue damage, and lipid peroxidation in liver and kidney. Therefore, the present study compared the curative effect of chlorophyll from Sauropus androgynus (L) Merr and Cu-chlorophyllin as antioxidant in NaNO2-induced female Wistar rats based on haematological, serum biochemical, and histological evaluation. Thirty male Wistar rats were randomly assigned into six groups of five rats each. NaNO2 were given at a subacute dose of 50 mg/kg bw intraperitoneally for 10 days. Chlorophyll from S. androgynus and Cu-chlorophyllin from K-Liquid™ were given in the following 14 days at the two doses: 0,016 mg/mL and 0.008 mg/mL. NaNO2 exposure resulted in significant reductions () in values of packed cell volume (PCV), haemoglobin (Hb) concentration and red blood cell (RBC) count, transferrin, and ferritin and elevation in malondialdehyde (MDA) level and schistocytes percentage with insignificant reductions in serum albumin and transferrin levels. Histology of kidney and liver were changed insignificantly () to normal values. Chlorophyll from S. androgynus and Cu-chlorophyllin possess antioxidant potentials to protect against toxicities induced by sodium nitrate. Suparmi Suparmi, Minidian Fasitasari, Martanto Martosupono, and Jubhar Christian Mangimbulude Copyright © 2016 Suparmi Suparmi et al. 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.