Effects Of Xenobiotics Research Articles

Lipid profile of blood serum in mice under conditions of bisphenol a administration and vitamin a different suplementation

The purpose of the study was to determine the lipid profile of blood serum and glucose tolerance in mice under conditions of bisphenol A (BPA) administration and different vitamin A consumption. The experimental animals were wild type mice with normal retinoids supplementation and transgenic mice (Lrat-/-) that are unable to esterify of retinol and do not have retinoid stores in liver. BPA, dissolved in corn oil (used as a vehicle), was administered per os daily for 3 days at a dose of 50 mg/kg body weight. Vitamin A overconsumption was modeled by administration of retinyl acetate in a very high dose of 3000 IU at 12 h intervals for 3 days. In the present study dyslipidemia was observed in the mice received 50 mg/kg BPA represented by significant higher triglycerides (at 1,4-fold), total cholesterol (at 2,2-fold), LDL-C, VLDL-C and HDL-C (46%, 39% and 2,8-fold respectively) than those mice of control group received vehicle. Administration of BPA also resulted in disruptions of glucose homeostasis, consisting of hyperglycemia (11±1.11 mmol/l) and glucose intolerance of animals. These BPA’s actions were attributed to its ability of binding to nonclassical membrane estrogen receptor as well as the G-protein coupled-receptor 30 (GPR30) and to act through nongenomic pathways. In knockout mice that did not have retinoid stores in the liver, indicators of both lipid profiles and glucose homeostasis were not significantly different from identical indicators of vehicle-treated mice. Additional 3000 IU retinyl acetate expose simultaneously with administration of 50 mg/kg BPA enhanced the lipogenic effect of xenobiotics in the wild type animals and induce its obesonic adverse effect in Lrat-/- mice. Thus, BPA exposure results in metabolic disorders consisting of hyperglycemia, glucose intolerance, hypercholesterolemia and hyperlipidemia. Retinoids enhanced the BPA action as an obesogen.

Co-Occurrence and Combinatory Effects of Alternaria Mycotoxins and other Xenobiotics of Food Origin: Current Scenario and Future Perspectives.

Mycotoxins are low-molecular weight compounds produced by diverse genera of molds that may contaminate food and feed threatening the health of humans and animals. Recent findings underline the importance of studying the combined occurrence of multiple mycotoxins and the relevance of assessing the toxicity their simultaneous exposure may cause in living organisms. In this context, for the first time, this work has critically reviewed the most relevant data concerning the occurrence and toxicity of mycotoxins produced by Alternaria spp., which are among the most important emerging risks to be assessed in food safety, alone or in combination with other mycotoxins and bioactive food constituents. According to the literature covered, multiple Alternaria mycotoxins may often occur simultaneously in contaminated food, along with several other mycotoxins and food bioactives inherently present in the studied matrices. Although the toxicity of combinations naturally found in food has been rarely assessed experimentally, the data collected so far, clearly point out that chemical mixtures may differ in their toxicity compared to the effect of toxins tested individually. The data presented here may provide a solid foothold to better support the risk assessment of Alternaria mycotoxins highlighting the actual role of chemical mixtures on influencing their toxicity.

Effect of Coagulation Factor Concentrates on Markers of Endothelial Cell Damage in Experimental Hemorrhagic Shock.

Plasma-based resuscitation showed protective effects on the endothelial glycocalyx compared with crystalloid resuscitation. There is paucity of data regarding the effect of coagulation factor concentrates (CFC) on the glycocalyx in hemorrhagic shock (HS). We hypothesized that colloid-based resuscitation supplemented with CFCs offers a therapeutic value to treat endothelial damage following HS. Eighty-four rats were subjected to pressure-controlled (mean arterial pressure (MAP) 30-35 mm Hg) and lab-guided (targeted cutoff: lactate >2.2. mmol/L and base deficit > 5.5 mmol/L) HS. Animals were resuscitated with fresh frozen plasma (FFP), human albumin (HA) or Ringer's lactate (RL) and RL or HA supplemented with fibrinogen concentrate (FC) or prothrombin complex concentrate (PCC). Serum epinephrine and the following markers of endothelial damage were assessed at baseline and at the end-of-observation (120 min after shock was terminated): syndecan-1, heparan sulfate, and soluble vascular endothelial growth factor receptor 1 (sVEGFR 1). Resuscitation with FFP had no effect on sVEGFR1 compared with crystalloid-based resuscitation (FFP: 19.3 ng/mL vs. RL: 15.9 ng/mL; RL+FC: 19.7 ng/mL; RL+PCC: 18.9 ng/mL; n.s.). At the end-of-observation, syndecan-1 was similar among all groups. Interestingly, HA+FC treated animals displayed the highest syndecan-1 concentration (12.07 ng/mL). Resuscitation with FFP restored heparan sulfate back to baseline (baseline: 36 ng/mL vs. end-of-observation: 36 ng/mL). The current study revealed that plasma-based resuscitation normalized circulating heparan sulfate but not syndecan-1. Co-administration of CFC had no further effect on glycocalyx shedding suggesting a lack of its therapeutic potential. VExperimental in vivo study.

PROBLEMS AND PROSPECTS OF TRAINING SPECIALISTS IN PREVENTIVE TOXICOLOGY

The new chemical threats, existing and constantly emerging to public health require the improvement of the system of training specialists in the field of preventive toxicology. Preventive toxicology is an independent discipline. However, medical and preventive doctors carrying out hygienic regulation, assessment of toxicity and hazard of chemicals and dealing with prevention and risk assessment of the effects of xenobiotics on human health, have only basic toxicology training. Currently, in the nomenclature of the professional standard in the specialty “Medical and Preventive Business”, the specialty “Preventive Toxicology” is absent, and the number of hours allocated for studying this section is very limited.Diploma education in the field of preventive toxicology is carried out on the basis of the Federal State Educational Standard of Higher Education in the specialty “Medical and Preventive care”, within the framework of which specialized hygienic disciplines with components of preventive toxicology are taught. At the postgraduate education stage, issues of chemical safety and preventive toxicology are addressed only in selected educational institutions, for example, on certification cycles in hygienic specialties, as well as on short-term specialized advanced training cycles.At the Department of Human Ecology and Environmental Hygiene of the I.M. Sechenov First Moscow State Medical University, a separate training module on preventive toxicology was developed and introduced into the educational process. One of the main objectives of the development of this curriculum was the formation of the students’ algorithms for conducting toxicological research and approaches to the evaluation of the results. At this stage of the training, students study in-depth laboratory toxicological methods, the adaptation mechanisms of the organism, and questions of extrapolation of human data obtained in animal experiments, the pathogenesis of intoxication and long-term effects of exposure to harmful substances. The analysis of the system of training specialists in the field of preventive toxicology suggests the need to improve the forms and methods of teaching students, primarily through the development of skills to work with data registries and toxicological laboratories, using the capabilities of research institutes and institutions of the of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare

CERTAIN PARACLINICAL INDICATORS IN NEWBORN PATIENTS WITH SEPSIS, WHOSE PARENTS HAVE CONSTANTLY LIVED UNDER DIFFERENT ECOLOGICAL CONDITIONS

Xenobiotics can have various effects on the human body, and especially on the course of fetal development. Numerous researchers point out that the nature of the external environment can negatively affect the course of certain diseases in both children and adults. Neonatal sepsis is one of the most serious diseases in neonatological practice and in our opinion is a completely unexplained topic of the impact of adverse environmental factors on the characteristics of sepsis in newborns, depending on the environmental situation of their parents. The aim of the study was to investigate the features of individual indicators of a pair of clinical trials in children with neonatal sepsis, whose parents lived permanently in different environmental conditions. Material and methods. To study this goal, a comprehensive survey of 260 newborns who in 2015-2018 suffered from neonatal sepsis. The proposed environmental risk factor (ERF) was a group-forming feature of a comprehensive assessment of the long-term load on the body of parents of newborns of anthropogenic pollution of air, water and soil in the regions, taking into account the environmental situation in regional centers. Thus, the first clinical group (main) included patients with neonatal sepsis, whose parents lived permanently in months with ERF 2.0 and more and with unfavorable environmental characteristics of the regional center. The second group (comparison) was formed by newborns with sepsis, whose parents lived permanently in areas with a low risk of adverse effects of these environmental factors on their body (ERF<2.0). Results and discussion. The content in the serum of patients with neonatal sepsis interleukins-6, -8.-10, Creactive protein, presepsin and procalcitonin reflected the activity of the systemic inflammatory response of the body to the infectious agent. It should be noted that patients of clinical group I were more likely to have a high serum content of interleukin-10, which has an anti-inflammatory effect. Thus, the content of this interleukin .35.0 pg / ml in the blood occurred in the newborn of the main group in 23.7 % of cases, and in children of the comparison group – in 18.1 % of cases. Along with a clearer definition of patients with group I high levels of anti-inflammatory interleukin-10, in newborns found a significant decrease in serum concentrations of immunoglobulins of classes A, G, M. Conclusions. The decrease in the level of these serum immunoglobulins is probably due to the immunosuppressive effect of xenobiotics on the fetus, whose mother was in the conditions of long-term action of xenobiotics. This, in turn, reduces the body's resistance of the newborn to infection and contributes to a more severe course of the infectious process. Probably, more severe manifestations of neonatal sepsis in neonates of the I clinical group are partly due to a combination of decreased immunoglobulin synthesis and increased production of interleukin-10.

MORPHOLOGICAL PECULIARITIES OF RAT BONE MARROW UNDER THE INFLUENCE OF NITRATE SALTS IN INCREASED CONCENTRATIONS

The study of the qualitative composition of water and food products revealed the increased concentration of nitrates in their composition. Nitric acid salts in toxic doses can lead to disorders of the endocrine system, blood circulation, central nervous system, etc. Bone marrow is one of the most sensitive organs, which is responsible for the formation of cellular elements of blood. The object of our research was to study the morphological peculiarities of the bone marrow of rats under the influence of nitrate salts on the body and to determine the regularities of subacute and chronic hemotoxic effect of xenobiotics on the process of granulocyto-, erythrocyto- and thrombocytopoiesis. The study was conducted on 48 mature male rats. Nitrate Na (NaNO3) was used as xenobiotic. The animals were removed from the experiment on 10th, 30th and 90th day. The qualitative and quantitative composition of the parenchymatous and stromal component of the bone marrow was studied on the samples, stained with hematoxylin and eosin. During the experiment, the most expressed changes were observed in erythron: reduced number of nuclear cells in erythroid islands, signs of their diserythropoiesis – focal vacuolization, abnormal shape and size of the nuclei, their fragmentation, pathological inclusions in cytoplasm. Changes in granulocytopoiesis were expressed by the disturbance of their stratification – precursors with different degree of maturity were present in all parts of the medullary canal. Changes in megakaryocytes were expressed by their focal accumulation in the form of clusters and partial dislocation, regarding the sinusoids. The observations on animals revealed the term-dependent nature of changes in the bone marrow. On the 90th day, a progression of qualitative and quantitative changes in hematopoietic tissue was determined. The hemotoxic effect was expressed by disorders in the maturation of all its precursors – the ratio of parenchyma-stroma was still reduced, dysplastic changes in erythron increased, focal dystrophic changes in the stromal component of the bone marrow were observed.

The Mechanisms of Formation of Immunodeficiency's, Autoimmune Reactions and Hypersensitivity under the Influence of Xenobiotics

In the last 30-40 years, a new scientific direction has been formed, which is studying the effect of xenobiotics on the nonspecific resistance of the organism and the immune system immunotoxicology. The subject of immunotoxicology is the study of the effect on the immune homeostasis of xenobiotics: toxic chemicals (TCh), pharmacological agents and biological agents [1-3]. At the same time, damage to the immune system can be the result of both direct and indirect effects of xenobiotics and/or their metabolites. In addition, xenobiotics (or their metabolites) can develop an immune response with the formation of antibodies. It should be noted, and the possibility of modification of toxic compounds, as a result of which they acquire the properties of antigen. It is also possible the formation of antibodies to the complex toxicant-antigen [1-4].

РЕЗУЛЬТАТЫ СКРИНИНГОВОЙ ОЦЕНКИ ПИЩЕВОЙ ЦЕННОСТИ И СОДЕРЖАНИЯ АМИНОКИСЛОТ В РАЦИОНАХ ПИТАНИЯ РАБОЧИХ

To decrease the toxic effects of xenobiotics on healthy workers in healthful and dietary meals, it’s important to consider not only the proper diet intake of macro- and micronutrients, but protein quality in terms of essential amino acids. A study was conducted to evaluate nutritional value and amino acids content in the industrial workers diets of two metallurgical enterprises by calculation and laboratory methods. We found that set of healthful and dietary meals at the calculation stage do not comply with regulatory requirements for fats and carbohydrates by 34 and 16 percent, respectively. According to laboratory tests, from 57 to 68 percent of sets of healthful and dietary meals do not comply with regulatory requirements for proteins, fats and carbohydrates. The discrepancy in the data on the amount of determined nutrients between the calculated and laboratory methods may be due to calculation errors, shortage and quality of raw materials, as well as a limitation of methods for determining fat and carbohydrates. With a set of healthful and dietary meals workers can satisfy the almost daily requirement for the corresponding energy expenditures for some amino acids, however, the required amount of these amino acids in workers in contact with heavy metals has not been established. It has also been found that in diets of healthful and dietary meals, the ratio of tryptophan / lysine / methionine + cystine is violated towards an excess of tryptophan, whose deamination products are highly toxic. It is necessary to continue further investigation of ready-made diets of healthful and dietary meals for nutritional value and amino acid content in order to identify factors affecting the discrepancy within research results between calculation and laboratory methods, as well as establish adequate norms for amino acids intake in workers exposed to toxic substances.

Precision-Cut Tissue Slices (PCTS) from the digestive gland of the Mediterranean mussel Mytilus galloprovincialis: An ex vivo approach for molecular and cellular responses in marine invertebrates

The precision-cut tissue slices (PCTS) represent a largely used biological model in mammalian research. This ex vivo approach offers the main advantages of in vitro systems, while maintaining the natural architecture of the tissue. The use of PCTS in toxicological research has been proposed for investigating the cellular effects of xenobiotics or bioactive compounds mostly in mammalian models. Their application is increasing also in marine organisms, but still limited to fish. This work validates the use of PCTS in an invertebrate species, the Mediterranean mussel Mytilus galloprovincialis. Intact tissue slices of different thicknesses (300, 350 and 400 μm) were successfully obtained from the digestive gland. The slices maintained the histological integrity and the viability after 6 h and 24 h incubation in culture medium, with some differences depending on the thickness. The enzymatic activities and mRNA levels of catalase and glutathione S-transferase, chosen as model biological endpoints, were measured until 24 h incubation, revealing the functionality of such systems. This work demonstrates the suitability of mussel PCTS for investigating molecular and cellular responses in ecotoxicological research.

Level of Osteotropic Elements in the Jaw Bones of Experimental Animals in Terms of the Impact of Xenobiotics

Pollution of the environment with heavy metals, pesticides, nitrates leads to an unceasing deterioration of the population’s health, in particular, the dental one. Excessive intake of salts of heavy metals and nitrites is accompanied by changes in calcium-phosphorus metabolism rates, indicating a disorder of metabolic processes in bone tissue. This necessitates the study of the level of osteotropic elements of the jaw bone tissue.
 Materials and methods of research. In the experiment on 80 white outbred male rats, the effects of cadmium chloride, sodium nitrite and their combined action on the content of osteotropic elements in the jaw bone were studied. The control group consisted of 10 intact animals.
 Results. It was determined that in the dynamics (1st, 14th, 28th days) of both cadmium-nitrite, nitrite and cadmium intoxication there was observed the accumulation of cadmium and decrease of calcium, copper, zinc levels in bone tissue of animal jaws compared to intact group.
 Conclusions.The most significant changes in the level of osteotropic elements in the jaw bones are found in the combined effect of xenobiotics, which is important for understanding of the metabolic processes in the oral cavity.

TO THE MECHANISM OF SEASONAL VARIATIONS IN CARBON TETRACHLORIDE TOXICITY

Introduction. Seasonal biorhythms can modify the toxic effect of xenobiotics. Natural fluctuations in hormone levels in the blood which can modify the metabolic processes in the liver can be the base of one of the mechanisms in this phenomenon. The study of the effector role of testosterone in seasonal chrono-reactivity can reveal one new link in the pathogenesis and will improve health risk assessment, especially in patients taking hormone therapy. The aim of the study was to reveal the role of testosterone in the mechanisms of chrono-reactivity the toxic effect for carbon tetrachloride in warm-blooded animals. Material and Methods. Studies were conducted on adult male Wistar rats, divided into negative control groups, a model with CCl4-induced toxic hepatitis, and experimental in which CCl4 exposure was carried out following a preliminary 7-day course of testosterone administration. Direct and total bilirubin, cholesterol, alkaline phosphatase, AlAT and AsAT, hydroperoxide and malondialdehyde were determined by standard methods. The experiment was repeated twice: both in winter and spring. Results. The amplitude of the damage to the structures and functions of hepatocytes from a single injection of the same poison dosage in winter and spring manifested in varying degrees, revealing the modulatory role of biological rhythms. Under premedication with testosterone, a similar tendency was observed in both series of the experiment (winter, spring): the toxic effect of CCl4 increased. This was recorded by the following biochemical changes: bilirubin increased by 55%, cholesterol - 19%, alkaline phosphatase - 12%, AlAT - 17%, AsAT - 35%, hydroperoxide - 29%, and malonic dialdehyde slightly (relative to groups with model toxic hepatitis). Conclusion. The male sex hormone regulating the metabolic activation of cytochromes in hepatocytes performing biotransformation is one of the effector links in the seasonal chrono-reactivity phenomena. The discovery of the whole mechanism will allow developing an effective system of chronoprophylaxis and reducing the risks of toxic poisoning in individuals during periods of maximum chrono-reactivity.

Indinavir Increases Midazolam N-Glucuronidation in Humans: Identification of an Alternate CYP3A Inhibitor Using an In Vitro to In Vivo Approach.

Midazolam is a widely used index substrate for assessing effects of xenobiotics on CYP3A activity. A previous study involving human hepatocytes showed the primary route of midazolam metabolism, 1'-hydroxylation, shifted to N-glucuronidation in the presence of the CYP3A inhibitor ketoconazole, which may lead to an overprediction of the magnitude of a xenobiotic-midazolam interaction. Because ketoconazole is no longer recommended as a clinical CYP3A inhibitor, indinavir was selected as an alternate CYP3A inhibitor to evaluate the contribution of the N-glucuronidation pathway to midazolam metabolism. The effects of indinavir on midazolam 1'-hydroxylation and N-glucuronidation were first characterized in human-derived in vitro systems. Compared with vehicle, indinavir (10 μM) inhibited midazolam 1'-hydroxylation by recombinant CYP3A4, human liver microsomes, and high-CYP3A activity cryopreserved human hepatocytes by ≥70%; the IC50 obtained with hepatocytes (2.7 μM) was within reported human unbound indinavir Cmax (≤5 μM). Midazolam N-glucuronidation in hepatocytes increased in the presence of indinavir in both a concentration-dependent (1-33 μM) and time-dependent (0-4 hours) manner (by up to 2.5-fold), prompting assessment in human volunteers (n = 8). As predicted by these in vitro data, indinavir was a strong inhibitor of the 1'-hydroxylation pathway, decreasing the 1'-hydroxymidazolam/midazolam area under the plasma concentration versus time curve (AUC)0-12h ratio by 80%. Although not statistically significant, the midazolam N-glucuronide/midazolam AUC0-12h ratio increased by 40%, suggesting a shift to the N-glucuronidation pathway. The amount of midazolam N-glucuronide recovered in urine increased 4-fold but remained <10% of the oral midazolam dose (2.5 mg). A powered clinical study would clarify whether N-glucuronidation should be considered when assessing the magnitude of a xenobiotic-midazolam interaction.

Toxicity of food contact paper evaluated by combined biological and chemical methods

The study was focused on assessment of potential health risks of paper-based food contact materials (FCMs) in a step-wise approach using three toxicological bioassays in vitro and chemical analyses of migrating contaminants. 3T3 NRU cytotoxicity test showed high sensitivity to detect basal toxicity of FCMs extracts and served as a first-line test for selection of samples for further testing. The reconstructed human intestine model EpiIntestinal showed more realistic tissue response than cell culture monolayer and higher resistance despite prolonged exposure to the selected 6 samples, i.e. negligible decrease of viability and intestinal penetration, nevertheless an increase of IL-8 after exposure to black printed sample extract. Yeast based assays identified weak agonistic/antagonostic activity to human androgen receptor of the black printed sample. In accordance with the biological effects, the targeted LC and GC analytical methods confirmed the presence of high amounts of phthalates, photoinitiators and PAHs that could justify the hazard of the black printed sample. Heavily printed uncoated FCMs are recognized not to be suitable for direct contact with food. The selected bioassays and chemical analyses might be useful tools to detect targeted biological effects of xenobiotics suspected to contribute to human exposure from food.

Amitriptyline at an Environmentally Relevant Concentration Alters the Profile of Metabolites Beyond Monoamines in Gilt-Head Bream.

The antidepressant amitriptyline is a widely used selective serotonin reuptake inhibitor that is found in the aquatic environment. The present study investigates alterations in the brain and the liver metabolome of gilt-head bream (Sparus aurata) after exposure at an environmentally relevant concentration (0.2 µg/L) of amitriptyline for 7 d. Analysis of variance-simultaneous component analysis is used to identify metabolites that distinguish exposed from control animals. Overall, alterations in lipid metabolism suggest the occurrence of oxidative stress in both the brain and the liver-a common adverse effect of xenobiotics. However, alterations in the amino acid arginine are also observed. These are likely related to the nitric oxide system that is known to be associated with the mechanism of action of antidepressants. In addition, changes in asparagine and methionine levels in the brain and pantothenate, uric acid, and formylisoglutamine/N-formimino-L-glutamate levels in the liver could indicate variation of amino acid metabolism in both tissues; and the perturbation of glutamate in the liver implies that the energy metabolism is also affected. These results reveal that environmentally relevant concentrations of amitriptyline perturb a fraction of the metabolome that is not typically associated with antidepressant exposure in fish. Environ Toxicol Chem 2019;00:1-13. © 2019 SETAC.

Aryl Hydrocarbon Receptor: Its Regulation and Roles in Transformation and Tumorigenesis.

AhR is an environmental response gene that mediates cellular responses to a variety of xenobiotic compounds that frequently function as AhR ligands. Many AhR ligands are classified as carcinogens or pro-carcinogens. Thus, AhR itself acts as a major mediator of the carcinogenic effect of many xenobiotics in vivo. In this concise review, mechanisms by which AhR trans-activates downstream target gene expression, modulates immune responses, and mediates malignant transformation and tumor development are discussed. Moreover, activation of AhR by post-translational modifications and crosstalk with other transcription factors or signaling pathways are also summarized.

Understanding antimicrobial discovery and resistance from a metagenomic and metatranscriptomic perspective: advances and applications.

Our inability to cultivate most microorganisms, specifically bacteria, in the laboratory has for many years restricted our view and understanding of the bacterial meta-resistome in all living and nonliving environments. As a result, reservoirs, sources and distribution of antibiotic resistance genes (ARGS) and antibiotic-producers, as well as the effects of human activity and antibiotics on the selection and dissemination of ARGs were not well comprehended. With the advances made in the fields of metagenomics and metatranscriptomics, many of the hitherto little-understood concepts are becoming clearer. Further, the discovery of antibiotics such as lugdinin and lactocillin from the human microbiota, buttressed the importance of these new fields. Metagenomics and metatranscriptomics are becoming important clinical diagnostic tools for screening and detecting pathogens and ARGs, assessing the effects of antibiotics, other xenobiotics and human activity on the environment, characterizing the microbiome and the environmental resistome with lesser turnaround time and decreasing cost, as well as discovering antibiotic-producers. However, challenges with accurate binning, skewed ARGs databases, detection of less abundant and allelic variants of ARGs and efficient mobilome characterization remain. Ongoing efforts in long-read, phased- and single-cell sequencing, strain-resolved binning, chromosomal-conformation capture, DNA-methylation binning and deep-learning bioinformatic approaches offer promising prospects in reconstructing complete strain-level genomes and mobilomes from metagenomes.

Genotoxic assessment of selected native plants to deferentially exposed urban ecosystems.

The aim of this study is to provide an analysis of the impact of ecogenotoxicity on native flora abortivity in various urban areas. In which, there was an analysis of 5 groupings of locations with a differing environmental load intensity within the city of Bratislava (Slovakia) over a 2-year period. Our results show varying data depending on the proximity of each site relating to a direct source of pollution and the potential impact of localized wind currents on the distribution of pollutants in the urban environment. The highest value of pollen abortivity in the city was observed in a group of locations exposed to heavy traffic pollution loads. Abortivity of native flora near heavy traffic road areas correlated with the imissions data measured in the same area. Wind-exposed uncovered sites also experienced higher values of native flora abortivity. These results confirmed the varying intensity of genotoxic impact in differing localities and also suggest that xenobiotic effects on flora can occur remotely from the original source of pollution.

Oxidative Response and Micronucleus Centromere Assay in HEp-2 Cells Exposed to Fungicide Iprodione.

The fungicide agents are a key component in the fruits and vegetables production. The Iprodione residues are one of the pesticide more frequently found in food products. The available data about the cytotoxicity of iprodione and its metabolites are scarce and do not allow characterization of its genotoxic potential and define the risk assessment.The human larynx epidermoid carcinoma cell line (HEp-2) has been shown to be sensitive to the toxic effects of xenobiotics of different origin and have been often used in citotoxicity and genotoxicity studies. The purpose of this paper is to evaluate the induction of genotoxicity and the role of oxidative stress in HEp-2cell line by exposure to the IP. The MTT test for viability resulted in CL50 85.86 (77.05-95.68) μg/mL of Iprodione. On the basis of this result, we proceeded to expose the cells to the sublethal concentrations (below the CL50) during 24 h to analyze the mitotic index and nuclear division index in order to determine the subcytotoxic concentrations of IP which the genotoxicity was evaluated. The subcytotoxic concentrations of 7, 17, and 25 μg/mL IP induced aneugenic effects as micronuclei centromere positive whereas 17 μg/mL was a threshold for centromere negative micronuclei induction in HEp-2 cells. The abnormal mitosis was induced for exposition of Hep-2 cells to the three concentrations. According to the result obtained, citotoxicity and genotoxicity oxidative stress studies were performed in 1.5, 7.0, and 25 μg/mL of IP. The results showed that the GSH intracellular content, the SOD activity and the levels of oxidative damage of the proteins were affected lead to redox imbalance. The decreased in the SOD activity and protein oxidation were in according to the result obtained to genotoxicity, suggesting that different biological targets could be affected.

Cytokine expression and lymphocyte proliferative capacity in diseased harbor porpoises (Phocoena phocoena) – Biomarkers for health assessment in wildlife cetaceans

Harbor porpoises (Phocoena phocoena) in the North and Baltic Seas are exposed to anthropogenic influences including acoustic stress and environmental contaminants. In order to evaluate immune responses in healthy and diseased harbor porpoise cells, cytokine expression analyses and lymphocyte proliferation assays, together with toxicological analyses were performed in stranded and bycaught animals as well as in animals kept in permanent human care. Severely diseased harbor porpoises showed a reduced proliferative capacity of peripheral blood lymphocytes together with diminished transcription of transforming growth factor-β and tumor necrosis factor-α compared to healthy controls. Toxicological analyses revealed accumulation of polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT) in harbor porpoise blood samples. Correlation analyses between blood organochlorine levels and immune parameters revealed no direct effects of xenobiotics upon lymphocyte proliferation or cytokine transcription, respectively. Results reveal an impaired function of peripheral blood leukocytes in severely diseased harbor porpoises, indicating immune exhaustion and increased disease susceptibility.

Toxicological pitfalls in ICU practice.

Either analgosedation or central nervous system dysfunction may be a side effect of implemented pharmacological treatment, as well as a consequence of intentional or unintentional poisoning. In traumatic lesions or anoxia of the central nervous system, a question arises after a recommended follow-up period about the effects of xenobiotics on nervous system function. Although therapeutic drug monitoring is the gold standard in such cases, usually a single toxicological estimation of "a neurodepressive compound" is performed after treatment discontinuation in order to determine the type and amount of exogenous substances, or their metabolites, in a patient's bodily fluids, which allows for an assessment of its actual effects on central nervous system functions. The aim of this paper was to describe the aspects of diagnostic toxicology which are essential for improved determination of the type and amount of exogenous substances present in biological fluids of intensive care patients. We present examples of clinical cases in order to discuss the most common discrepancies in interpretation related to the ordering of toxicology tests.