Journal of Toxicology The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . 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. Circadian Rhythms and Breast Cancer: The Role of Per2 in Doxorubicin-Induced Cell Death Tue, 11 Aug 2015 10:22:28 +0000 Mammalian circadian rhythms form an integral physiological system allowing for the synchronisation of all metabolic processes to daily light/dark cycles, thereby optimising their efficacy. Circadian disruptions have been implicated in the onset and progression of various cancers, including those arising in the breast. Several links between the circadian protein Per2 and DNA damage responses exist. Aberrant Per2 expression results in potent downstream effects on both cell cycle and apoptotic targets, suggestive of a tumour suppressive role for Per2. Due to the severe dose limiting side effects associated with current chemotherapeutic strategies, including the use of doxorubicin, a need for more effective adjuvant therapies to increase cancer cell susceptibility has arisen. This study was therefore aimed at characterizing the role of Per2 in normal breast epithelia (MCF-12A) and in ER− breast cancer cells (MDA-MB-231) and also at determining the role of Per2 in doxorubicin-induced cell death. In both cell lines Per2 protein expression displayed a 24-hour circadian rhythm in both cell lines. Per2 was located predominantly in the cytoplasm, with nuclear localization observed with lower cytoplasmic fluorescent intensities. Our results show that Per2 silencing effectively sensitizes the chemoresistant MDA-MB-231 breast cancer cells to the cytotoxic effects of doxorubicin. Megan I. Mitchell and Anna-Mart Engelbrecht Copyright © 2015 Megan I. Mitchell and Anna-Mart Engelbrecht. All rights reserved. Intoxication by Cyanide in Pregnant Sows: Prenatal and Postnatal Evaluation Tue, 26 May 2015 14:17:25 +0000 Cyanide is a ubiquitous chemical in the environment and has been associated with many intoxication episodes; however, little is known about its potentially toxic effects on development. The aim of this study was to evaluate the effects of maternal exposure to potassium cyanide (KCN) during pregnancy on both sows and their offspring. Twenty-four pregnant sows were allocated into four groups that orally received different doses of KCN (0.0, 2.0, 4.0, and 6.0 mg/kg of body weight) from day 21 of pregnancy to term. The KCN-treated sows showed histological lesions in the CNS, thyroid follicle enlargement, thyroid epithelial thickening, colloid reabsorption changes, and vacuolar degeneration of the renal tubular epithelium. Sows treated with 4.0 mg/kg KCN showed an increase in the number of dead piglets at birth. Weaned piglets from all KCN-treated groups showed histological lesions in the thyroid glands with features similar to those found in their mothers. The exposure of pregnant sows to cyanide thus caused toxic effects in both mothers and piglets. We suggest that swine can serve as a useful animal model to assess the neurological, goitrogenic, and reproductive effects of cyanide toxicosis. André T. Gotardo, Isis M. Hueza, Helena Manzano, Viviane M. Maruo, Paulo C. Maiorka, and Silvana L. Górniak Copyright © 2015 André T. Gotardo et al. All rights reserved. Species Differences in Paraoxonase Mediated Hydrolysis of Several Organophosphorus Insecticide Metabolites Sun, 15 Feb 2015 08:52:47 +0000 Paraoxonase (PON1) is a calcium dependent enzyme that is capable of hydrolyzing organophosphate anticholinesterases. PON1 activity is present in most mammals and previous research established that PON1 activity differs depending on the species. These studies mainly used the organophosphate substrate paraoxon, the active metabolite of the insecticide parathion. Using serum PON1 from different mammalian species, we compared the hydrolysis of paraoxon with the hydrolysis of the active metabolites (oxons) of two additional organophosphorus insecticides, methyl parathion and chlorpyrifos. Paraoxon hydrolysis was greater than that of methyl paraoxon, but the level of activity between species displayed a similar pattern. Regardless of the species tested, the hydrolysis of chlorpyrifos-oxon was significantly greater than that of paraoxon or methyl paraoxon. These data indicate that chlorpyrifos-oxon is a better substrate for PON1 regardless of the species. The pattern of species differences in PON1 activity varied with the change in substrate to chlorpyrifos-oxon from paraoxon or methyl paraoxon. For example, the sex difference observed here and reported elsewhere in the literature for rat PON1 hydrolysis of paraoxon was not present when chlorpyrifos-oxon was the substrate. Russell L. Carr, Mary Beth Dail, Howard W. Chambers, and Janice E. Chambers Copyright © 2015 Russell L. Carr et al. All rights reserved. Fertilizers and Mixed Crop Cultivation of Chromium Tolerant and Sensitive Plants under Chromium Toxicity Thu, 29 Jan 2015 14:17:50 +0000 Zea mays (maize) and Vigna radiata (green gram) are found to be the chromium (Cr) tolerant and sensitive plants, respectively. In the present paper, we investigate the reduction of the toxicity of Cr in the sensitive plants by the mixed crop cultivation in the field using various amendments. Further, the potassium dichromate was used as the source of hexavalent Cr. The results indicated that Cr adversely affects both the growth and yield of plants. The soil properties vary with Cr and different fertilizer amendments and the yield of both plants were affected by Cr. We conclude that metal accumulation of seeds of green gram was higher than corn and the application of single fertilizer either farm yard manure (FYM) or nitrogen, phosphorous, and potassium (NPK) enhances the growth and yield of both the tolerant and sensitive plants in the mixed crop cultivations. B. Dheeba, P. Sampathkumar, and K. Kannan Copyright © 2015 B. Dheeba et al. All rights reserved. Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines Wed, 21 Jan 2015 07:06:21 +0000 The association of autism spectrum disorders with oxidative stress, redox imbalance, and mitochondrial dysfunction has become increasingly recognized. In this study, extracellular flux analysis was used to compare mitochondrial respiration in lymphoblastoid cell lines (LCLs) from individuals with autism and unaffected controls exposed to ethylmercury, an environmental toxin known to deplete glutathione and induce oxidative stress and mitochondrial dysfunction. We also tested whether pretreating the autism LCLs with N-acetyl cysteine (NAC) to increase glutathione concentrations conferred protection from ethylmercury. Examination of 16 autism/control LCL pairs revealed that a subgroup (31%) of autism LCLs exhibited a greater reduction in ATP-linked respiration, maximal respiratory capacity, and reserve capacity when exposed to ethylmercury, compared to control LCLs. These respiratory parameters were significantly elevated at baseline in the ethylmercury-sensitive autism subgroup as compared to control LCLs. NAC pretreatment of the sensitive subgroup reduced (normalized) baseline respiratory parameters and blunted the exaggerated ethylmercury-induced reserve capacity depletion. These findings suggest that the epidemiological link between environmental mercury exposure and an increased risk of developing autism may be mediated through mitochondrial dysfunction and support the notion that a subset of individuals with autism may be vulnerable to environmental influences with detrimental effects on development through mitochondrial dysfunction. Shannon Rose, Rebecca Wynne, Richard E. Frye, Stepan Melnyk, and S. Jill James Copyright © 2015 Shannon Rose et al. All rights reserved. Cytotoxicity and Genotoxicity of Panel of Single- and Multiwalled Carbon Nanotubes: In Vitro Effects on Normal Syrian Hamster Embryo and Immortalized V79 Hamster Lung Cells Mon, 08 Dec 2014 12:13:55 +0000 Carbon nanotubes (CNTs) belong to a specific class of nanomaterials with unique properties. Because of their anticipated use in a wide range of industrial applications, their toxicity is of increasing concern. In order to determine whether specific physicochemical characteristics of CNTs are responsible for their toxicological effects, we investigated the cytotoxic and genotoxic effects of eight CNTs representative of each of the commonly encountered classes: single- SW-, double- DW-, and multiwalled (MW) CNTs, purified and raw. In addition, because most previous studies of CNT toxicity were conducted on immortalized cell lines, we decided to compare results obtained from V79 cells, an established cell line, with results from SHE (Syrian hamster embryo) cells, an easy-to-handle normal cell model. After 24 hours of treatment, MWCNTs were generally found to be more cytotoxic than SW- or DWCNTs. MWCNTs also provoked more genotoxic effects. No correlation could be found between CNT genotoxicity and metal impurities, length, surface area, or induction of cellular oxidative stress, but genotoxicity was seen to increase with CNT width. The toxicity observed for some CNTs leads us to suggest that they might also act by interfering with the cell cycle, but no significant differences were observed between normal and immortalized cells. C. Darne, F. Terzetti, C. Coulais, C. Fontana, S. Binet, L. Gaté, and Y. Guichard Copyright © 2014 C. Darne et al. All rights reserved. Anion Gap Toxicity in Alloxan Induced Type 2 Diabetic Rats Treated with Antidiabetic Noncytotoxic Bioactive Compounds of Ethanolic Extract of Moringa oleifera Mon, 08 Dec 2014 07:12:26 +0000 Moringa oleifera (MO) is used for a number of therapeutic purposes. This raises the question of safety and possible toxicity. The objective of the study was to ascertain the safety and possible metabolic toxicity in comparison with metformin, a known drug associated with acidosis. Animals confirmed with diabetes were grouped into 2 groups. The control group only received oral dose of PBS while the test group was treated with ethanolic extract of MO orally twice daily for 5-6 days. Data showed that the extract significantly lowered glucose level to normal values and did not cause any significant cytotoxicity compared to the control group (); there was no gain in weight between the MO treated and the control groups (). However, data showed that treatment with an ethanolic extract of MO caused a decrease in bicarbonate (), and more than twofold increase in anion gap (); metformin treatment also decreased bicarbonate () and resulted in a threefold increase in anion gap (). Conclusively, these data show that while MO appears to have antidiabetic and noncytotoxic properties, it is associated with statistically significant anion gap acidosis in alloxan induced type 2 diabetic rats. Maxwell Omabe, Chibueze Nwudele, Kenneth Nwobini Omabe, and Albert Egwu Okorocha Copyright © 2014 Maxwell Omabe et al. All rights reserved. Camel Milk Beneficial Effects on Treating Gentamicin Induced Alterations in Rats Wed, 03 Dec 2014 00:10:09 +0000 The potential effect of camel milk (CM) against gentamicin (GM) induced biochemical changes in the rat serum was evaluated. Four groups of six albino rats were used for control, CM fed, injected with GM(i.p.), and then fed and injected with GM. The results showed that the administration of GM significantly altered the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activity in rat serum. CM restored these parameters to almost their normal range in group IV. Additionally, the present study showed that injection of rats with gentamicin caused an increase in malondialdehyde (MDA) and myeloperoxidase (MPO) activity while the antioxidant enzymes like superoxide dismutase (SOD) and glutathione s-transferase (GST) activity decreased significantly (). Administration of CM significantly () inhibited the formation of MDA and activity of MPO and upregulated the antioxidant enzymes (SOD and GST) activity. The overall findings of this study demonstrated that pretreatment with CM gave protection against GM induced hepatic damage possibly by inhibiting oxidative stress and inflammation, and hence camel milk can be identified as a new therapeutic agent. Abdulrahman K. Al-Asmari, R. Abbasmanthiri, Abdulrahman M. Al-Elewi, Saud Al-Omani, Saeed Al-Asmary, and Sarah A. Al-Asmari Copyright © 2014 Abdulrahman K. Al-Asmari et al. All rights reserved. Trace and Essential Elements Analysis in Cymbopogon citratus (DC.) Stapf Samples by Graphite Furnace-Atomic Absorption Spectroscopy and Its Health Concern Mon, 01 Dec 2014 00:10:07 +0000 Cymbopogon citratus (DC.) Stapf commonly known as lemon grass is used extensively as green tea and even as herbal tea ingredient across the world. Plants have the ability to uptake metals as nutrient from the soil and its environment which are so essential for their physiological and biochemical growth. Concentrations of these twelve trace elements, namely, Mg, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Mo, As, Cd, and Pb, are analysed by graphite furnace-atomic absorption spectroscopy (GF-AAS) and are compared with the permissible limits of FAO/WHO, ICMR, and NIH, USA, which are found to be within permissible limits. Toxic metals like As, Cd, and Pb, analysed are within the tolerable daily diet limit and at low concentration. Jasha Momo H. Anal Copyright © 2014 Jasha Momo H. Anal. All rights reserved. Conditioned Medium Reconditions Hippocampal Neurons against Kainic Acid Induced Excitotoxicity: An In Vitro Study Sun, 23 Nov 2014 00:00:00 +0000 Stem cell therapy is gaining attention as a promising treatment option for neurodegenerative diseases. The functional efficacy of grafted cells is a matter of debate and the recent consensus is that the cellular and functional recoveries might be due to “by-stander” effects of grafted cells. In the present study, we investigated the neuroprotective effect of conditioned medium (CM) derived from human embryonic kidney (HEK) cells in a kainic acid (KA) induced hippocampal degeneration model system in in vitro condition. Hippocampal cell line was exposed to KA (200 µM) for 24 hrs (lesion group) whereas, in the treatment group, hippocampal cell line was exposed to KA in combination with HEK-CM (KA + HEK-CM). We observed that KA exposure to cells resulted in significant neuronal loss. Interestingly, HEK-CM cotreatment completely attenuated the excitotoxic effects of KA. In HEK-CM cotreatment group, the cell viability was ~85–95% as opposed to 47% in KA alone group. Further investigation demonstrated that treatment with HEK-CM stimulated the endogenous cell survival factors like brain derived neurotrophic factors (BDNF) and antiapoptotic factor Bcl-2, revealing the possible mechanism of neuroprotection. Our results suggest that HEK-CM protects hippocampal neurons against excitotoxicity by stimulating the host’s endogenous cell survival mechanisms. Pradeep Kumar K. Bevinahal, Chaitra Venugopal, Harish Chandra Prasad S. Yencharla, Shashank Chandanala, Raju R. Trichur, Sathyaprabha N. Talakad, Ramesh R. Bhonde, and Anandh Dhanushkodi Copyright © 2014 Pradeep Kumar K. Bevinahal et al. All rights reserved. Ameliorating Effects of Iron and Zinc on Vigna mungo L. Treated with Tannery Effluent Wed, 19 Nov 2014 00:00:00 +0000 Different dilutions, that is, 25, 50, 75, and 100%, of tannery effluent (TE) were chosen for the present study to assess the phytotoxic effects on Vigna mungo L. For amelioration purposes, different levels and combinations of iron and zinc were supplied to the plants along with 50% TE that is chosen on the basis of prior test under Petri dish culture. Cytotoxic and biochemical analysis and plant tolerance index (PTI) of plant were observed. Mitotic index deceased with increase in effluent concentration whereas abnormality % was increased. The pigments (chlorophyll a, total, and carotenoids) were decreased with increasing treatment levels of TE at both growth stages. However, carotenoid content increased significantly at all dilution levels of TE after first growth stage. Chlorophyll b was increased significantly after 35 days of growth but decreased after 70 days. The protein contents were also significantly decreased with increase in all TE treatments and increased significantly in zinc recovery treatments. Activities of catalase and peroxidase enzymes were significantly affected and increased significantly with effluent treatments. PTI showed an enhanced tolerance capacity of plant with treatment of iron and zinc. A negative correlation was found () between plant height and different dilutions of effluent whereas it was positively correlated () with iron and zinc treatments. The study represents the ameliorative effect of iron and zinc for phytotoxic damage in V. mungo caused by tannery effluent. Shefali Srivastava, Kumkum Mishra, and Pramod Kumar Tandon Copyright © 2014 Shefali Srivastava et al. All rights reserved. Xylazine as a Drug of Abuse and Its Effects on the Generation of Reactive Species and DNA Damage on Human Umbilical Vein Endothelial Cells Tue, 11 Nov 2014 06:57:20 +0000 Human xylazine (XYL) abuse among addicts has received great interest due to its potential toxic effects upon addicts and the need to understand the mechanism of action associated with the potential health effects. XYL is an alpha-2 agonist restricted to veterinarian applications, without human medical applications. Our previous work demonstrated that XYL and its combination with cocaine (COC) and/or 6-monoacetylmorphine (6-MAM) induce cell death through an apoptotic mechanism. The aim of this study was to determine the effect of xylazine on the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as well as DNA damage on endothelial cell. Human umbilical vein endothelial cells (HUVEC) were treated with XYL (60 μM), COC (160 μM), 6-MAM (160 μM), camptothecin (positive control, 50 μM), XYL/COC (50 μM), XYL/6-MAM (50 μM), and XYL/COC/6-MAM (40 μM) for a period of 24 hours. Generation of intracellular ROS, RNS, and DNA fragmentation were analyzed using a fluorometric assay. Results reveal that XYL and 6-MAM increase levels of ROS; no induction of RNS production was observed. The combination of these drugs shows significant increase in DNA fragmentation in G2/M phase, while XYL, COC, and 6-MAM, without combination, present higher DNA fragmentation in G0/G1 phase. These findings support that these drugs and their combination alter important biochemical events aligned with an apoptotic mechanism of action in HUVEC. Luz Silva-Torres, Christian Veléz, Lyvia Álvarez, and Beatriz Zayas Copyright © 2014 Luz Silva-Torres et al. All rights reserved. In Vitro Reporter Assays for Screening of Chemicals That Disrupt Androgen Signaling Sun, 09 Nov 2014 09:45:13 +0000 Endocrine disruptive chemicals (EDCs) modulate hormone signaling and cause developmental and reproductive anomalies. Today, there is a global concern regarding endocrine disruption effects, particularly those mediated by the androgen receptor (AR). Androgen or male hormones are critical for the development and maintenance of male characteristics and numerous EDCs exist in the environment with the potential to disrupt androgen action. The threat is more during critical developmental windows when there is increased sensitivity to these compounds. Timely screening and detection of the EDCs is essential to minimize deleterious effects produced by these toxic chemicals. As a first line of screening, in vitro transcription assays are very useful due to their speed, convenience, and cost effectiveness. In this paper, recent in vitro reporter assays for detecting androgenic or antiandrogenic activity of EDCs have been reviewed. Two important cell systems used for this purpose, namely, the mammalian or yeast cell systems, have been discussed. Use of reporter genes such as bacterial luciferase (lux) and green fluorescent protein (gfp) has significantly improved speed and sensitivity of detection. Also, many of the current reporter assay systems can be used in a high throughput format allowing speedy evaluation of multiple potential EDCs at a lower price. Gargi Bagchi Bhattacharjee and S. M. Paul Khurana Copyright © 2014 Gargi Bagchi Bhattacharjee and S. M. Paul Khurana. All rights reserved. Lipid Profile and Oxidative Stress Markers in Wistar Rats following Oral and Repeated Exposure to Fijk Herbal Mixture Mon, 20 Oct 2014 09:34:56 +0000 This study determined the effect of the oral and repeated administration of Fijk herbal mixture on rat biochemical and morphological parameters. Twenty-four Wistar rats were distributed into four groups of 6. Group A served as control and received oral administration of distilled water daily. The experimental groups B, C, and D were daily and orally exposed to Fijk herbal mixture at 15, 30, and 45 mg/kg, respectively. Treatments lasted for 21 days. The rats were sacrificed under mild diethyl ether anesthesia 24 hr after cessation of treatment. The blood and liver samples were collected and used for the biochemical and morphological analyses. Oral exposure to Fijk caused elevated levels of rat plasma ALT, AST, triglycerides, LDL, and MDA. In contrast, rat plasma HDL, GSH, and ALP levels were lowered by Fijk oral exposure. Also, the herbal remedy caused a dose-dependent elevation in the plasma atherogenic index. The histopathology examinations of rat liver sections revealed inimical cellular alterations caused by repeated exposure to Fijk. Study provides evidence that oral and repeated exposure to Fijk in rats raised the atherogenic index and potentiated oxidative stress as well as hepatic injury. Oluyomi Stephen Adeyemi and Bukola Temitope Orekoya Copyright © 2014 Oluyomi Stephen Adeyemi and Bukola Temitope Orekoya. All rights reserved.