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Environmental Toxicology and Pharmacology
Journal Prestige (SJR): 0.813
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  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1382-6689
Published by Elsevier Homepage  [3177 journals]
  • Impact of cadmium toxicity on cartilage loss in a 3D in vitro
    • Abstract: Publication date: Available online 30 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Yessica Eduviges Zamudio-Cuevas, Gabriela Martínez-Nava, Daniel Reyes-Hinojosa, L. Mendoza-Soto, Javier Fernández-Torres, Alberto López-Reyes, Anell Olivos-Meza, María Aurora Armienta-Hernández, Esther Aurora Ruíz-Huerta, María de Jesús González-Guadarrama, Bertha Vargas Sandoval, Carlos Landa-Solís, Roberto Sánchez-Sánchez, C. Suarez-Ahedo, Carlos Alberto Lozada-Pérez, María Concepción Gutiérrez-Ruiz, Denise Clavijo-Cornejo, Carlos Pineda, L. Jacobo-Albavera, M. Domínguez-PérezABSTRACTOsteoarthritis (OA) is the gradual loss of articular cartilage and decrease in subchondral space. One of the risk factors Exposure to cadmium (Cd) through tobacco smoke has been identified as a major OA risk factor. There are no reports addressing the role of Cd in OA progression at the molecular level. Our findings revealed that Cd can promote the activation of metalloproteinases (MMP1, MMP3, MMP9 y MMP13), affecting the expression of COL2A1 and ACAN, and decreasing the presence of glycosaminoglycans and proteoglycans through an inflammatory response related to IL-1β y a IL-6, as well as oxidative by producing ROS like O2-• and H2O2. In conclusion, our findings suggest a cytotoxic role of Cd in the articular cartilage, which could affect OA development.
  • Prenatal exposure to the pesticide metam sodium induces sensorimotor and
           neurobehavioral abnormalities in mice offspring
    • Abstract: Publication date: Available online 27 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Nour-eddine Kaikai, Saadia Ba-M’hamed, Mohamed Bennis, Abderrazzak GhanimaAbstractThe present study has investigated developmental neurotoxicity of Metam sodium (MS), from gestational day 6 and throughout the gestation period until delivery. Therefore, mated female mice were orally exposed on a daily basis to 0 (control), 50, 100 or 150 mg of MS/kg of body weight and their standard fertility and reproductive parameters were assessed. The offspring were examined for their sensorimotor development, depression and cognitive performance. Our results showed that MS exposure during pregnancy led to one case of mortality, two cases of abortion and disturbed fertility and reproductive parameters in pregnant dams. In offspring, MS induced an overall delay in innate reflexes and sensorimotor performances. Furthermore, all prenatally treated animals showed an increased level of depression-like behavior as well as a pronounced cognitive impairment in adulthood. These results demonstrated that prenatally exposure to MS causes a long-lasting developmental neurotoxicity and alters a wide range of behavioral functions in mice.
  • Potential risk of organophosphate exposure in male reproductive system of
           a non-target insect model Drosophila melanogaster
    • Abstract: Publication date: Available online 27 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Moutushi Mandi, Salma Khatun, Prem Rajak, Abhijit Mazumdar, Sumedha RoyBased on several adverse reports of pesticides on reproductive efficiency of various organisms, studies on “reproductive toxicity” have gained importance. Fecundity, reflecting reproductive success of any organism, is governed by several factors from female and male reproductive systems. This present study explored morphological and biochemical alterations in the male reproductive system of a non-target model organism, Drosophila melanogaster following chronic sub-lethal exposure (1st instar larvae differentially exposed to 1-6 µg/mL until adulthood) to the organophosphate (OP) pesticide, acephate (LC50 8.71 µg/mL). This study demonstrates altered testis structure, decreased germ cell viability and gross body weight, increased activities of oxidative stress markers lipid peroxidase (LPO), and the endogenous antioxidant enzyme catalase (CAT), and altered expression of reproductive marker proteins like vitellogenin and mitoferrin in acephate-exposed flies when compared to control counterparts. Altered reproductive behavior, indicated by a significant decline in the number of mating pairs, validates the adverse effect of chronic acephate exposure on male reproduction in the non-target insect model D. melanogaster.Graphical abstractGraphical abstract for this articleThe plate represents the findings of the entire study. Study demonstrates that chronic sub-lethal acephate exposure causes significant alteration in male reproductive structures, physiology and behavior which have been reflected through the alterations in the studied parameters. The results confirm that the altered expressions of the selected parameters might be the reason for the compromised male reproductive efficiency in the non-target model organism, Drosophila melanogaster following chronic acephate exposure.
  • Allicin modulates diclofenac sodium induced hepatonephro toxicity in rats
           via reducing oxidative stress and caspase 3 protein expression
    • Abstract: Publication date: Available online 23 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Sahar Hassan Orabi, Doaa Abdallah, Azza Hassan, Hesham Saad El Sabagh, Mabrouk Attia Abd EldaimAbstractPurposeThis study was designed to evaluate the protective effects of allicin against diclofenac sodium induced hepatonephro toxicity in rats.MethodsSixty male Wister albino rats were assigned into six groups. The control group received calcium carbonate and corn starch. 2nd group received diclofenac sodium (2 mg/kg bw orally) for 30 days. 3rd group received allicin (45 mg/kg bw orally) for 30 days. 4th group administrated diclofenac sodium as in the 2nd group and allicin (15 mg/kg bw orally) for 30 days. 5th group received diclofenac sodium as in the 2nd group and allicin (30 mg/kg bw orally) for 30 days. 6th group received diclofenac sodium as 2nd and allicin (45 mg/kg bw orally) for 30 days.ResultsDiclofenac sodium significantly elevated activities of serum aspartate aminotransferase and alanine aminotransferase and serum levels of creatinine and urea. In addition, it induced hyperglycemia, lipid peroxidation, pathological alteration and caspase 3 protein expression in hepatic and renal tissues. However, it decreased reduced glutathione concentration and proliferating cell nuclear antigen protein expression in hepatic tissues. In contrast, allicin modulated the diclofenac sodium induced alteration in liver and kidney functions and structures dose dependently.ConclusionThis study indicated that allicin had potential preventive effects against diclofenac sodium induced hepatonephro toxicity in rats.
  • Biomarkers of occupational exposure to pesticides: Systematic review of
    • Abstract: Publication date: Available online 22 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Suelen Pizzolatto Dalmolin, Danielly Bassani Dreon, Flavia Valladão Thiesen, Eliane DallegraveAbstractIntroductionPesticides are widely used around the world, and rural workers have greater risk of poisoning. The use of biomarkers for insecticides can contribute to the diagnosis and prevention of poisoning.ObjectiveTo identify, in the scientific literature, the biomarkers of occupational exposure to insecticides of different insecticide classes.MethodsThe PubMed, Lilacs and Embase databases were analyzed using a systematic search strategy and in accordance with the criteria established by the PRISMA methodology. Articles with information related to the use of biomarkers to identify active ingredients, or insecticide metabolites, or effects on the human biological matrices were analyzed.ResultsA total of 840 studies was found, and 30 met the selection criteria. The search identified 118 results for insecticide biomarkers, of which 45% were of exposure, 42% of effect, and 14% of susceptibility. Additionally, 78 were possible biomarkers, and only 67 confirmed to be different biomarkers for insecticides. Acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 3,5,6-trichloro-2-pyridinol (TCP-y), specific for Chlorpyrifos, were among the most common biomarkers identified; however, most metabolites found were non-specific.ConclusionVarious insecticide biomarkers were mentioned; nonetheless, only a few are specific and used to identify the wide range of insecticides to which farm workers are exposed.
  • L-glutamine supplementation exerts cardio-renal protection in
           estrogen-progestin oral contraceptive-treated female rats
    • Abstract: Publication date: Available online 22 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Kehinde Samuel Olaniyi, Isaiah Woru Sabinari, Lawrence Aderemi OlatunjiAbstractGlycogen and lipid disruptions represent a spectrum of metabolic disorders that are crucial risk factors for cardiovascular disease in estrogen-progestin oral contraceptive (COC) users. L-glutamine (GLN) has been shown to exert a modulatory effect in metabolic disorders-related syndromes. We therefore hypothesized that GLN supplementation would protect against myocardial and renal glycogen-lipid mishandling in COC-treated animals by modulation of Glucose-6-phosphate dehydrogenase (G6PD) and xanthine oxidase (XO) activities.Adult female Wistar rats were randomly allotted into control, GLN, COC and COC + GLN groups (six rats per group). The groups received vehicle (distilled water, p.o.), GLN (1 g/kg), COC containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and COC plus GLN respectively, daily for 8 weeks.Data showed that treatment with COC led to metabolically-induced obesity with correspondent increased visceral and epicardial fat mass. It also led to increased plasma, myocardial and renal triglyceride, free fatty acid, malondialdehyde (MDA), XO activity, uric acid content and decreased glutathione content and G6PD activity. In addition, COC increased myocardial but not renal glycogen content, and increased myocardial and renal glycogen synthase activity, increased plasma and renal lactate production and plasma aspartate transaminase/alanine aminotransferase (AST/ALT) ratio. However, these alterations were attenuated when supplemented with GLN except plasma AST/ALT ratio.Collectively, the present results indicate that estrogen-progestin oral contraceptive causes metabolically-induced obesity that is accompanied by differential myocardial and renal metabolic disturbances. The findings also suggest that irrespective of varying metabolic phenotypes, GLN exerts protection against cardio-renal dysmetabolism by modulation of XO and G6PD activities.
  • Pulmonary toxicity of Fe2O3, ZnFe2O4, NiFe2O4 and NiZnFe4O8 nanomaterials:
           inflammation and DNA strand breaks
    • Abstract: Publication date: Available online 21 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Niels Hadrup, Anne T. Saber, Zdenka O. Kyjovska, Nicklas R. Jacobsen, Minnamari Vippola, Essi Sarlin, Yaobo Ding, Otmar Schmid, Håkan Wallin, Keld A. Jensen, Ulla VogelAbstractExposure to metal oxide nanomaterials potentially occurs at the workplace. We investigated the toxicity of two Fe-oxides: Fe2O3 nanoparticles and nanorods; and three MFe2O4 spinels: NiZnFe4O8, ZnFe2O4, and NiFe2O4 nanoparticles. Mice were dosed 14, 43 or 128 µg by intratracheal instillation. Recovery periods were 1, 3, or 28 days. Inflammation – neutrophil influx into bronchoalveolar lavage (BAL) fluid – occurred for Fe2O3 rods (1 day), ZnFe2O4 (1, 3 days), NiFe2O4 (1, 3, 28 days), Fe2O3 (28 days) and NiZnFe4O8 (28 days). Conversion of mass-dose into specific surface-area-dose showed that inflammation correlated with deposited surface area and consequently, all these nanomaterials belong to the so-called low-solubility, low-toxicity class. Increased levels of DNA strand breaks were observed for both Fe2O3 particles and rods, in BAL cells three days post-exposure. To our knowledge, this is, besides magnetite (Fe3O4), the first study of the pulmonary toxicity of MFe2O4 spinel nanomaterials.
  • Investigating the protective actions of D-pinitol against arsenic-induced
           toxicity in PC12 cells and the underlying mechanism
    • Abstract: Publication date: Available online 21 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Shiblur Rahaman, Mahmuda Akter, Mostafizur Rahman, Tajuddin Sikder, Toshiyuki Hosokawa, Takeshi Saito, Masaaki KurasakiArsenic is awfully toxic metalloid responsible for many human diseases all over the world. Contrastingly, D-pinitol is a naturally occurring bioactive dietary compound has antioxidant properties. The objective of this study is to elucidate the protective actions of D-pinitol on arsenic-induced cytotoxicity and explore its controlling role in biomolecular mechanisms in PC12 cells. Obtained results demonstrated that co-exposure of D-pinitol with arsenic increases cell viability, decreases DNA damage and protects PC12 cells from arsenic-induced cytotoxicity by increasing glutathione (GSH) level and glutathione reductase (GR). Protein expression of western blot analysis showed that co-exposure of D-pinitol and arsenic significantly inhibited arsenic-induced autophagy which further suppressed apoptosis through up-regulation of survival factors; mTOR, p-mTOR, Akt, p-Akt, NF-кB, Nrf2, ERK1, GR, Bcl-x and down-regulation of death factors; p53, Bax, cytochrome c, LC3, although arsenic regulated those factors negatively. These results of this study suggested that D-pinitol protects PC12 cells from arsenic-induced cytotoxicity.Graphical abstractGraphical abstract for this article
    • Abstract: Publication date: Available online 21 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Ron van der Oost, David J. McKenzie, Frank Verweij, Carl Satumalay, Natascha van der Molen, Matthew J. Winter, J. Kevin ChipmanAbstractThe European City Fish project aimed to develop a generic methodology for ecological risk assessment for urban rivers. Since traditional methods only consider a small fraction of substances present in the water cycle, biological effect monitoring is required for a more reliable assessment of the pollution status. A major challenge for environmental risk assessment (ERA) is the application of adverse outcome pathways (AOP), i.e. the linking of pollutant exposure via early molecular and biochemical changes to physiological effects and, ultimately, effects on populations and ecosystems.We investigated the linkage between responses at these different levels. Many AOP aspects were investigated, from external and internal exposure to different classes of micropollutants, via molecular key events (MKE) the impacts on organs and organisms (fish physiology), to changes in the population dynamics of fish. Risk assessment procedures were evaluated by comparing environmental quality standards, bioassay responses, biomarkers in caged and feral fish, and the impact on fish populations. Although no complete AOP was observed, indirect relationships linking pollutant exposure via MKE to impaired locomotion were demonstrated at the most polluted site near a landfill for chemical waste. The pathway indicated that several upstream key events requiring energy for stress responses and toxic defence are likely to converge at a single common MKE: increased metabolic demands. Both fish biomarkers and the bioanalytical SIMONI strategy are valuable indicators for micropollutant risks to fish communities.
  • Comparative effects of Mancozeb and Disulfiram-induced striated muscle
           myopathies in Long-Evans rats
    • Abstract: Publication date: Available online 16 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Olivia J. Stephenson, Louis D. TrombettaAbstractDithiocarbamates (DTCs) like mancozeb (MZ) and disulfiram (DS) are used throughout agriculture and medicine and have been implicated in neurotoxicity. Little research has been studied on the reported myopathies caused by these compounds. Their pathogenesis and mechanism of muscle toxicity has not been fully studied. The aim of this study is to investigate if DTCs alter striated muscle tissues in vivo. Long-Evans rats were treated with either MZ or DS followed by analysis of muscle biomarkers and metal levels. DS resulted in increases in serum lactate dehydrogenase (LDH), cardiac troponin, and myoglobin levels. Creatine kinase-MB serum levels decreased. Mancozeb only showed an increase in serum LDH. Both MZ and DS-treatment resulted in altered metal levels in the myocardium but not skeletal muscle. Ultrastructural alterations included damaged mitochondria and myofibril splitting. The presence of multivesicular bodies, and alterations of the intercalated disc were also seen.
  • Nanoecotoxicology study of the response of magnetic
           O-Carboxymethylchitosan loaded silver nanoparticles on Artemia salina
    • Abstract: Publication date: Available online 16 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Carla Albertina Demarchi, Luisa Mota da Silva, Anna Niedźwiecka, Anna Ślawska-Waniewska, Sabina Lewińska, Jacir Dal Magro, Jean Felipe Fossá Calisto, Rafael Martello, Clovis Antonio RodriguesAbstractMagnetic silver nanoparticles (MNPAg) are interesting nanotechnology materials with borderless environmental science, that can be used to disinfect water contaminated with pathogenic bacteria. The use of MNPAg leads to increased risk of nanomaterial contamination in the environment, especially natural water sources, with harmful effects on the ecosystem. This study investigating survival and enzyme activity of magnetic O-carboxymethylchitosan loaded silver nanoparticle on Artemia salina. The results showed that mortality increased with increasing concentrations of MNPAg. O-Carboxymethylchitosan loaded silver nanoparticles were found to be more toxic, with a LC50 of 902.1 mg/L for γ-Fe2O3/Ag without reducing agent. Accumulation of silver on Artemia salina depends on the type of nanoparticle. Accumulation of nanoparticle containing polymers (carboxymethylchitosan/γ-Fe2O3/Ag without reducing agent, carboxymethylchitosan/γ-Fe2O3/Ag reduced with sucrose and carboxymethylchitosan/γ-Fe2O3/Ag reduced with NaBH4) were found to be higher than γ-Fe2O3/Ag reduced with NaBH4, γ-Fe2O3/Ag reduced with sucrose and γ-Fe2O3/Ag without reducing agent under the same experimental conditions. The antioxidant enzyme (CAT, SOD and GST) activities increased slightly following exposure, indicating that the toxic effects are related to oxidative stress. The combined results so far indicate that MNPA does not have the potential to affect aquatic organisms when released into the ecosystem.
  • Individual and cellular responses of earthworms (Eisenia fetida) to
           endosulfan at environmentally related concentrations
    • Abstract: Publication date: Available online 12 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Yajing Shi, Yajuan Shi, Lisha ZhengThe presence of endosulfan at high levels in soils poses a potential risk for terrestrial ecosystems and human health via the food chain. Therefore, the effects of endosulfan at environmentally related doses on the terrestrial biota are of great concern. The present study measured the mortality, growth inhibition and ultrastructure of the stomach and skin of earthworms exposed to endosulfan at environmentally related concentrations to identify the individual and cellular effects of endosulfan on terrestrial biota. The results demonstrated that the growth inhibition of earthworms was significantly and positively correlated with the endosulfan dose and little mortality was found. The nuclei, microvilli and cuticles in the stomachs and skin cells of earthworms exhibited marked abnormalities. Endosulfan injured the ultrastructure of the nucleus even at low doses (0.5 mg·kg-1). Endosulfan seriously affected stomach microvilli and the cuticle structure of the skin, and this damage increased with increased exposure time and dose. Notably, cuticle damage was worse than the microvilli damage. These experiments demonstrated that the morphological changes in the tissue ultrastructure of the earthworm were more sensitive than growth inhibition, and these changes may be used as an early warning indicator of endosulfan pollution. The degree of damage to microvilli and cuticle is a promising bio-indicator to evaluate pesticide risk. The results of this study provide evidence of endosulfan toxicity and the importance of risk assessment on the terrestrial ecosystem.Graphic abstractGraphical abstract for this article
  • Rat liver and kidney post-mitochondrial dysfunction by addition of chronic
           mixed metal intoxication and hepatorenal wellness mediated by phenolic
           components from Croton zambiscus leaves
    • Abstract: Publication date: Available online 9 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): J.K Akintunde, S.A Ayeni, M.A Adeoye, A.O ShittuAbstractChronic exposure of mixed-metal intoxication has been associated with prolonged oxidative stress and severe hepatorenal damage. This present study demonstrates the hepatoprotective and renoprotective activity of Croton zambesicus (C-ZAMB) leaves, naturally occurring phenolic compounds against chronic mixed-metal (EOMABRSL) induced toxicity. 0.5 ml of EOMABRSL via oral route induced chronic hepatoxicity and nephrotoxicity on exposure for 98 days (non-withdrawal) and 70 days (withdrawal) by abnormal alteration in the levels of endogenous antioxidants. Moreover, EOMABRSL induced hepatorenal damage by increasing the markers of liver toxicity (ALT, AST, ALP, GGT and bilirubin) and kidney failure (creatinine, urea, uric acid, and renal electrolytes-Na+ and K+). Both non-withdrawal and withdrawal approaches of EOMABRSL-exposed animals exhibited hepatorenal dysfunctions by increasing the activity of eco-51-nucleotidase (51ENT) followed by the decreased in the activity of lactate dehydrogenase (LDH)-index of cellular ATP. These results were further supported by the histopathological examination of nephritic cells, hepatocytes and splenocytes, manifested by hepatocellular necrosis, swelling or degeneration of tubular kidney epithelial cells as well as coalescing splenic periarteriolar lymphoid sheaths (PALSs) and lymphoid haemosiderin. The chronic EOMABRSL intoxication was ameliorated by administration of phenolic antioxidants from C-ZAMB leaves. Therefore, our study supports the view that phenolic C-ZAMB leaves may mediate hepatorenal wellness on chronic exposure to mixed-metal intoxication
  • Multi-parametric analysis of ciprofloxacin toxicity at ecologically
           relevant levels: short- and long-term effects on Daphnia magna
    • Abstract: Publication date: Available online 9 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Ricardo Dionísio, David Daniel, Gilberto Dias de Alkimin, Bruno NunesAbstractThe increased presence of emergent compounds, such as pharmaceuticals drugs, in the aquatic compartment has been acknowledged as an evolving environmental issue whose consequences are not yet fully characterized. Specific classes of pharmaceutical drugs, such as fluoroquinolone antibiotics, can exert toxic effects to non-target species with ecological significance, since these compounds are environmentally stable and persistent, and may interact with some of the key physiologic processes of organisms. Despite such characteristics, knowledge about the effects of these drugs is still scarce, especially to non-target organisms. The present study aimed to evaluate the effects of chronic and acute exposures of the cladoceran Daphnia magna to the ciprofloxacin. Putative toxic effects were assessed, following acute and chronic exposures to ecologically relevant concentrations of ciprofloxacin, through enzymatic (cholinesterase – ChEs, catalase – CAT, glutathione S-transferases – GSTs) and non-enzymatic (thiobarbituric acid reactive substances – TBARS, glycogen – Gly) biomarkers. In addition, we also determined behavioural (swimming distance – SD) and morphological (body length of the first brood – BL1B) endpoints in animals exposed to this drug. Ciprofloxacin acute exposure resulted in increased CAT and ChEs activities, and inhibited GSTs activity. After chronic exposure, ChEs activity was significantly inhibited, while GSTs activity was significantly enhanced. TBARS levels were only increased at higher concentrations of ciprofloxacin. CAT activity and Gly content did not evidence a clear and significant pattern of variation. SD was slightly inhibited during dark cycles. BL1B presented a significant decrease for animals subjected to an intermediate concentration. Results showed that even ecologically relevant concentrations of ciprofloxacin may cause oxidative stress in individuals of D. magna. The present study showed important data that corroborate the occurrence of significant biochemical alterations in key features of an aquatic organism when exposed to relevant levels of a widely used antibiotic, establishing essential links between environmental exposure to this specific drug and putative toxic challenges that may result in irreversible changes and damages, especially at the individual level. However, changes in the size of neonates suggest that population alterations are likely to occur under real scenarios of chronic contamination by this drug.
  • Neurobehavioural and biochemical responses associated with exposure to
           binary waterborne mixtures of zinc and nickel in rats
    • Abstract: Publication date: Available online 6 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Isaac A. Adedara, Adedayo N. Adegbosin, Michael A. Abiola, Ajibola A. Odunewu, Olatunde Owoeye, Solomon E. Owumi, Ebenezer O. FarombiEnvironmental and occupational exposure to metal mixtures due to various geogenic and anthropogenic activities poses a health threat to exposed organisms. The outcome of systemic interactions of metals is a topical area of research because it may cause either synergistic or antagonistic effect. The present study investigated the impact of co-exposure to environmentally relevant concentrations of waterborne nickel (75 and 150 µg NiCl2/L) and zinc (100 and 200 µg ZnCl2/L) mixtures on neurobehavioural performance of rats. Locomotor, motor and exploratory activities were evaluated using video-tracking software during trial in a novel arena and thereafter, biochemical and histological analyses were performed using the cerebrum, cerebellum and liver. Results indicated that zinc significantly (p 
  • Comparative Cr, As and CCA induced cytotostaticity in mice kidney: a
           contribution to assess CCA toxicity
    • Abstract: Publication date: Available online 6 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Rita Cerejeira Matos, Helena Oliveira, Henrique M.A.C. Fonseca, Simone Morais, Bechan Sharma, Conceição Santos, Maria de Lourdes PereiraAbstractCCA (Chromium Copper Arsenate) treated wood, widely used in outdoor residential structures and playgrounds, poses considerable dangers of leaching of its components to the environment.In this study, mouse kidney samples were used to evaluate the effects of CCA, chromium trioxide (CrO3) and arsenic pentoxide (As2O5) on cell pathophysiology by flow cytometry. Samples were collected after 14, 24, 48 and 96 hours of animal exposure. While Cr had no statistically significant cytostatic effects, As2O5 induced a S-phase delay in animals exposed for 24 h, and over time a G0/G1 phase blockage. The effects of CCA in S-phase were similar, but more severe than those of As2O5. Since environmental and public health hazards due to the long durability of CCA-treated wood products, these data confirm that CCA has profoundly toxic effects on cell cycle, distinct from the compounds themselves. These cytostatic effects support cell cycle dynamics as a valuable endpoint to assess the toxicity of remaining CCA-treated infrastructures, and the expected increased waste stream over the coming decades.
  • Exposure to first line anti-tuberculosis drugs in prepubertal age reduces
           the quality and functional competence of spermatozoa and oocytes in Swiss
           albino mice
    • Abstract: Publication date: Available online 6 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Arpitha Rao, Guruprasad Nayak, Sandhya Kumari, Sneha Guruprasad Kalthur, Sadhana Mutalik, Srinivas Mutalik, Satish Kumar Adiga, Guruprasad KalthurPrepubertal male and female Swiss albino mice of both sex were administered with first-line anti-tuberculosis drugs (ATDs) viz; Rifampicin, Isoniazid, Pyrazinamide, Streptomycin and Ethambutol intraperitoneally, for 4 weeks. Two weeks after the completion of treatment, male mice were sacrificed to collect caudal spermatozoa and female mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to collect metaphase II (MII) oocytes from oviduct. Administration of ATDs not only decreased the count, motility and, nuclear maturity andbut also, increased the head abnormalities, mitochondrial damage and DNA damage in epididymal spermatozoa. Reduction in number of ovulated oocytes, iIncreased degeneration rate and altered distribution pattern of cytoplasmic organelles was observed in oocytes of female mice. Presence of ATDs in in- vitro maturation (IVM) medium increased abnormalities in meioticresulted in abnormal spindle organization (except ethambutol) without affecting nuclear maturation. In conclusion, the rResult of this study indicates that ATD's had varied degree of toxicity, all the ATDs have considerable adverse effect on the functional competence of male and female gametes, however, with varied degree of toxicity functional potential.Graphical abstractGraphical abstract for this article
  • Integrating In Vitro Testing and Physiologically-Based Pharmacokinetic
           (PBPK) Modelling for Chemical Liver Toxicity Assessment – a Case Study
           of Troglitazone
    • Abstract: Publication date: Available online 5 November 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Lin Yu, Hequn Li, Chi Zhang, Qiang Zhang, Jiabin Guo, Jin Li, Haitao Yuan, Lizhong Li, Paul Carmichael, Shuangqing PengAbstractIn vitro to in vivo extrapolation (IVIVE) for next-generation risk assessment (NGRA) of chemicals requires computational modeling and faces unique challenges. Using mitochondria-related toxicity data of troglitazone (TGZ), a prototype drug known for liver toxicity, from HepaRG, HepG2, HC-04, and primary human hepatocytes, we explored inherent uncertainties in IVIVE, including cell models, cellular response endpoints, and dose metrics. A human population physiologically-based pharmacokinetic (PBPK) model for TGZ was developed to predict in vivo doses from in vitro point-of-departure (POD) concentrations. Compared to the 200-800 mg/d dose range of TGZ where liver injury was observed clinically, the predicted POD doses for the mean and top one percentile of the PBPK population were 28-372 and 15-178 mg/d respectively based on Cmax dosimetry, and 185-2552 and 83-1010 mg/d respectively based on AUC. In conclusion, although with many uncertainties, integrating in vitro assays and PBPK modeling is promising in informing liver toxicity-inducing TGZ doses.
    • Abstract: Publication date: Available online 20 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Sutapa Sarkar, Firas Alhasson, Diana Kimono, Muayad Albadrani, Ratanesh K. Seth, Shuo Xiao, Dwayne E. Porter, Geoff I. Scott, Bryan Brooks, Mitzi Nagarkatti, Prakash Nagarkatti, Saurabh ChatterjeeAbstractNAFLD often results in cardiovascular, intestinal and renal complications. Previous reports from our laboratory highlighted NAFLD induced ectopic inflammatory manifestations in the kidney that gave rise to glomerular inflammation. Extending our studies, we hypothesized that existing inflammatory conditions in NAFLD could make the kidneys more susceptible to environmental toxicity. Our results showed that exposure of Microcystin-LR (MC) in NAFLD mice caused a marked increase in cellular scarring with a concomitant increase in mesangial cell activation as observed by increased α-SMA in the extracellular matrix surrounding the glomeruli. Renal tissue surrounding the glomeruli also showed increased NOX2 activation as shown by greater co-localization of p47 Phox and its membrane component gp91Phox both in the mesangial cell and surrounding tissue. Mechanistically, mesangial cells incubated with apocynin, nitrone spin trap DMPO and miR21 inhibitor showed significantly decreased α-SMA, miR21 levels and proinflammatory cytokine release in the supernatant. In parallel, mice lacking miR21, known to be activated by NOX2, when exposed to MC in NAFLD showed decreased mesangial cell activation. Strikingly, phenyl boronic acid incubated cells that were exposed to MC showed significantly decreased mesangial cell activation showing that peroxynitrite might be the major reactive species involved in mediation of the activation process, release of proinflammatory micro RNAs and cytokines that are crucial for renal toxicity. Thus, in conclusion, MC exposure causes NOX2 activation that leads to mesangial cell activation and toxicity via release of peroxynitrite that also represses PTEN by the upregulation of miR21 thus amplifying the toxicity.
  • Effects of common pharmaceutical drugs (paracetamol and acetylsalicylic
           acid) short term exposure on biomarkers of the mussel Mytilus spp
    • Abstract: Publication date: Available online 18 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Francisca Piedade, Sofia Bio, Bruno NunesAbstractPharmaceutical drugs in the wild may pose significant risks to non-target exposed organisms. This situation is even more troublesome for coastal marine or estuarine environments, located in the vicinity of large human conglomerates, for which the putative number of pollutants is extremely high, and the regime by which wild organisms are exposed is continuous. In addition, the number of studies addressing this issue is still scarce, despite evidences that show the potential contamination profiles and adverse biological effects in organisms from such areas. In this study, the ecotoxicity of common pharmaceutical drugs (namely paracetamol and acetylsalicylic acid) was assessed, by studying the susceptibility of the mussel species Mytilus spp to oxidative stress after being exposed for 96 h to increasing but ecologically relevant concentrations of the two mentioned pharmaceuticals (paracetamol: 0, 0.5, 5, 50, and 500 µg/L; acetylsalicylic acid: 0, 0.1, 1, 10, and 100 µg/L). The oxidative status in exposed organisms was analyzed by measuring oxidative stress biomarkers, namely catalase (CAT), glutathione-S-transferases (GSTs), and lipoperoxidation (LPO) levels, whose alteration was indicative of chemical exposure, in both digestive gland and gills of the organisms. In addition, the food uptake and the nutritional reserve status of exposed organisms were also assessed, by measuring the consumption of ingested food, and levels of tissue reserves of glycogen in gills and digestive gland. No significant alterations were observed in the assessed oxidative stress parameters so it was possible to hypothesize that the studied drugs may have probably exerted a limited alteration of antioxidant defenses and damage, which was reverted by the activation of defensive adaptive mechanisms. This set of data evidenced that the pro-oxidative metabolism that was already described for both drugs in other animal models, was not fully established in the exposed mussels. On the contrary, glycogen reserves were substantially changed after exposure to both toxicants, being possible to observe opposite responses caused by both drugs. Food uptake was not altered following exposure to the drugs. Further evaluations are thus required to conclude about both drugs ecotoxicity and other parameters, namely seasonality, which should be considered when performing ecotoxicology tests, especially with the selected species.
  • Effect of formalin in early stages of the freshwater neotropical catfish,
           Lophiosilurus alexandri
    • Abstract: Publication date: Available online 17 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Luanna do Carmo Neves, Kleber Campos Miranda Filho, João Paulo Silva Lorenzini, Cintia Labussière Nakayama, Ronald Kennedy LuzAbstractThe objective of this study was to evaluate the acute toxicity of formalin and its level of therapeutic safety in early stages of Lophiosilurus alexandri. Experiment 1, larvae 7 days after hatching (DAH) were exposed to 43.2, 86.4, 172.8, 345.6, 691.2, 1404.0 mg/L of formalin. Experiment 2, juveniles with 22 DAH exposed to 54, 108, 216, 432, 648 mg/L. Experiment 3, 45 DAH exposed to 86.4, 172.8, 345.6, 691.2, 1036.8 mg/L. The experiments had a control without addition of formalin and all were carried out in duplicate. The LC50-12 h were: Experiment 1 = 108.86 mg/L; 2: 152.74 mg/L; 3: 244.38 mg/L of formalin. The respective safety levels were: Experiment 1 = 66.22 mg/L (1 h), 10.89 mg/L (12 h); 2 = 49.17 mg/L (2 h), 15.27 mg/L (12 h); 3 = 68.89 mg/L (2 h), 24.44 mg/L (12 h). The results showed that the developmental stage influenced the sensitivity of animals to formalin.
  • Fluoride regulates the expression of extracellular matrix HSPG and related
           signaling pathways FGFR3 and Ihh/PTHrP feedback loop during endochondral
    • Abstract: Publication date: Available online 17 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Ying Gao, Fangzhong Gui, Demin Li, Ruixue Zhang, Qinyuan Sun, Xiaoying GuoAbstractSkeletal fluorosis causes growth plate impairment and growth retardation during bone development. Longitudinal bone development is accomplished by endochondral ossification in growth plate. However, the mechanism of fluoride impairs growth plate is unclear. To explore the effect of fluoride on various glycosaminoglycans (GAGs) and related signaling pathways in growth plate during endochondral ossification, SD rats and ATDC5 cells were treated with fluoride and carried out subsequent experiments. We found that the expression of heparan sulfate (HS), a kind of GAGs in extracellular matrix, was significantly increased in the growth plate of fluoride-treated rats compared with control rats. Furthermore, the expression of HS synthetic enzyme exostosin 1 (EXT1) and glypican 6 (GPC6), a core protein of HS proteoglycan (HSPG), were significantly increased in fluoride-treated ATDC5 cells compared with control cells (P 
  • Organochlorine pollutants’ levels in hair, amniotic fluid and serum
           samples of pregnant women in Greece. A cohort study
    • Abstract: Publication date: Available online 16 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Michail Barmpas, Elena Vakonaki, Manolis Tzatzarakis, Stauros Sifakis, Athanasios Alegakis, Themos Grigoriadis, Danielle Bittencourt Sodré, Georgios Daskalakis, Aristidis Antsaklis, Aristidis TsatsakisAbstractPersistent organic pollutants are synthetic chemicals highly resistant to degradation with strong tendency to bioaccumulation. Assessment of human exposure to these compounds is crucial for public health protection, especially during vulnerable periods.The aim of the present cohort study was to evaluate the level of contamination to PCBs, o,p’- and p,p’-DDE, o,p’ and p,p’-DDD, o,p’ and p,p’-DDT and HCB in pregnant women. Hair, amniotic fluid and serum samples were collected and analyzed by HS-SPME-GCMS.The most detected analytes in amniotic fluids were p,p’-DDE, p,p’-DDD, o,p’-DDE and PCB101, in serum p,p’-DDE, HCB and PCB101 and in hair p,p’-DDE, HCB and PCB101. The levels of HCB and PCB101 in amniotic fluids were positively correlated with those in hair. Higher levels of DDDs and DDTs in hair samples and PCB28 in amniotic fluids were observed in smoker pregnant women. Gestation age was inversely proportional with the detected levels of PCB101 in all tested samples.
    • Abstract: Publication date: Available online 16 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Silvia Santa Cruz, Gladis Magnarelli, María Gabriela RovedattiThe proximity to areas of intensive pesticide application is a risk factor that favors xenobiotic exposure. Pesticides may interfere with hormonal function and cause alterations in the reproductive system, pregnancy complications, and adverse fetal development. We evaluated potential endocrine disruption and the evolution of the third trimester of pregnancy in women residing in a rural area of Argentina with intense pesticide applications, and the characteristics of their newborns. Blood samples were collected from healthy women in the third trimester of pregnancy during the pesticide spraying (SP) (n = 26) and nonspraying (NSP) (n = 27) periods. Plasma cholinesterase activity and cortisol and DHEA-S levels were lower in SP than in NSP. The percentage of preterm premature rupture of membranes was higher in SP than in NSP. Macrosomia at birth was17% in both periods. This study reinforces the importance of preventing potential cases of cumulative toxicity during the perinatal period through monitoring and epidemiological studies.Graphical abstractGraphical abstract for this article
  • Bioconcentration and depuration of cadmium in the selected tissues of rare
           minnow (Gobiocypris rarus) and the effect of dietary mulberry leaf
           supplementation on depuration
    • Abstract: Publication date: Available online 15 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Xiaoqin Xiong, Haiying Li, Ning Qiu, Liangxia Su, Zhenli Huang, Lirong Song, Jianwei WangA 56-day trial was conducted to elucidate the bioconcentration and depuration of Cd in the liver and muscle of rare minnows (Gobiocypris rarus) and determine the effect of dietary mulberry leaf supplementation on depuration. Juvenile rare minnows were exposed to environmentally relevant doses of Cd (1 and 10 µg/L) for 28 days of uptake and then allowed 28 days of depuration. The bioaccumulation factors of the treated rare minnows in the liver and muscle were calculated to be between 4.13–4.675 and 1.76–1.94, respectively. This results suggested that Cd had high potential for bioconcentration in rare minnows. To investigate the effect of dietary mulberry leaf supplementation on depuration, the remaining fish of each group were allowed to depurate with different ratios (0%, 10%, and 30% dry weight) of dietary mulberry leaf supplementation for an additional 28 days. Fish weights did not differ significantly (p >  0.05) between the control and mulberry leaf treated groups. Mulberry leaf powder did not significantly affect Cd depuration in the 10 µg/L group or in the muscle of the 1 µg/L group, but caused a significant decrease in Cd content in the liver of the 1 µg/L group (p 
  • Diesel exhaust particle and dust mite induced airway inflammation is
           modified by cerium dioxide nanoparticles
    • Abstract: Publication date: Available online 11 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Kirsty Meldrum, Sarah Robertson, Isabella Römer, Tim Marczylo, Timothy W. Gant, Rachel Smith, Teresa D. Tetley, Martin O. LeonardAbstractCerium dioxide nanoparticles (CeO2NPs) have been used as diesel fuel-borne catalysts for improved efficiency and pollutant emissions. Concerns that such material may influence diesel exhaust particle (DEP) effects within the lung we examined responses in mice with and without exposure to house dust mite (HDM). Repeated intranasal instillation of combined HDM and DEP increased airway mucin, eosinophils, lymphocytes, IL-5, IL-13, IL-17A and plasma IgE, which were further increased with CeO2NPs co-exposure. A single co-exposure of CeO2NPs and DEP after repeated HDM exposure increased macrophage and IL-17A levels above DEP induced levels. CeO2NPs exposure in the absence of HDM also resulted in increased levels of plasma IgE and airway mucin staining, changes not observed with RPT DEP exposure alone. These observations indicate that CeO2NPs can modify exhaust particulate and allergen induced inflammatory events in the lung with the potential to influence conditions such as allergic airway disease.
  • Plastic Pollution in the Environment
    • Abstract: Publication date: Available online 11 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s):
  • Biochemical responses revealed in an amphibian species after exposure to a
           forgotten contaminant: An integrated biomarker assessment
    • Abstract: Publication date: Available online 10 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): S. Dahms-Verster, A. Nel, J.H.J. van Vuren, R. GreenfieldAbstractVanadium is a metal whose toxicity towards terrestrial and aquatic species has been under-reported to date.. The biochemical responses of vanadium in amphibian species have not been determined. To establish the effects of vanadium (V) on exposed adult Xenopus laevis, acute and chronic exposures were conducted, and biomarker analyses were performed on liver and muscle tissues from exposed frogs. Biomarkers of exposure, such as acetylcholinesterase (AChE) and metallothioneins (MT), were analysed. Biomarkers of effect were also analysed to determine possible increases in reactive oxygen species (ROS), and the effect of the exposure on the energy balance in the organisms. These included superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), protein carbonyls (PC), malondialdehyde (MDA), and cellular energy allocation (CEA) (energy available, energy consumption, lipids, proteins and glucose). In acute exposures, the energy balances in organisms were distinctly affected, possibly due to insulin mimetic properties of V. In chronic exposures, MT, AChE, SOD, CAT and GSH responses were more pronounced. Although AChE is generally inhibited by pollutant exposure, in this study, it was stimulated. There were significant inhibitions of SOD and CAT, previously observed in frog species. PC levels increased in the highest acute exposure concentration, indicating protein damage. The IBR.v2 revealed the biochemical responses of V more effectively than traditional statistical analysis.
  • Tributyltin Reduces Bone Mineral Density by Reprograming Bone Marrow
           Mesenchymal Stem Cells in Rat
    • Abstract: Publication date: Available online 7 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Wenhuan Yao, Xinglong Wei, Hao Guo, Dong Cheng, Hui Li, Limin Sun, Shu’e Wang, Dongmei Guo, Yanli Yang, Jiliang SiTributyltin (TBT), a proven endocrine disrupter, was widely used in industry and agriculture. Previous research showed that TBT could alter the balance between osteogenesis and adipogenesis, which may have significant consequences for bone health. Herein, we exposed male rats to TBT chloride (TBTCl) to evaluate the deleterious effects of TBT on bone. Exposure to 50 μg kg-1 TBT resulted in a significant decrease in bone mineral density (BMD) at the femur diaphysis region in the rat. A dose-dependent increase in lipid accumulation and adipocyte number was observed in the bone marrow (BM) of the femur. Meanwhile, TBTCl treatment significantly enhanced the expression of PPARγ and attenuated the expression of Runx2 and β-catenin in BM. In addition, serum ALP activity of TBT-exposed rats also showed a dose-dependent decrease. These results suggest that TBT could reduce BMD via inhibition of the Wnt/β-catenin pathway and skew the adipo-osteogenic balance in the BM of rats.Graphical abstractGraphical abstract for this article
  • Increased surface area of halloysite nanotubes due to surface modification
           predicts lung inflammation and acute phase response after pulmonary
           exposure in mice
    • Abstract: Publication date: Available online 1 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Kenneth Klingenberg Barfod, Katja Maria Bendtsen, Trine Berthing, Antti Joonas Koivisto, Sarah Søs Poulsen, Ester Segal, Eveline Verleysen, Jan Mast, Andreas Holländer, Keld Alstrup Jensen, Karin Sørig Hougaard, Ulla VogelAbstractThe toxicological potential of halloysite nanotubes (HNTs) and variants after functional alterations to surface area are not clear. We assessed the toxicological response to HNTs (NaturalNano (NN)) before and after surface etching (NN-etched). Potential cytotoxicity of the two HNTs was screened in vitro in MutaTMMouse lung epithelial cells. Lung inflammation, acute phase response and genotoxicity were assessed 1, 3, and 28 days after a single intratracheal instillation of adult female C57BL/6 J BomTac mice. The doses were 6, 18 or 54 µg of HNTs, compared to vehicle controls and the Carbon black NP (Printex 90) of 162 µg/mouse. The cellular composition of bronchoalveolar lavage (BAL) fluid was determined as a measure of lung inflammation. The pulmonary and hepatic acute phase responses were assessed by Saa3 mRNA levels in lung and liver tissue by real-time quantitative PCR. Pulmonary and systemic genotoxicity were analyzed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The etched HNT (NN-etched) had 4-5 times larger BET surface area than the unmodified HNT (NN). Instillation of NN-etched at the highest dose induced influx of neutrophils into the lungs at all time points and increased Saa3 mRNA levels in lung tissue on day 1 and 3 after exposure. No genotoxicity was observed at any time point. In conclusion, functionalization by etching increased BET surface area of the studied NN and enhanced pulmonary inflammatory toxicity in mice.
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