Pharmacokinetics of praziquantel and its metabolites in grass carp (Ctenopharyngodon idella) following the oral administration of a single bolus.

The study aimed to evaluate and compare the routes and rates of the depletion of the antiparasitic praziquantel (PZQ), a derivative of pyrazinoisoquinoline, following its oral administration in grass carp (Ctenopharyngodon idella). We focused on the depletion of PZQ and its major metabolites - cis-hydroxy praziquantel (CPZQ) and trans-hydroxy praziquantel (TPZQ), in water, the plasma, hepatopancreas, kidney, muscle, and skin, following a single oral administration of PZQ in a concentration of 50 mg/kg. Fish were sampled before the drug administration and then eight times in the course of the 30-day-long experiment. Our results indicate the rapid absorption and elimination of PZQ and its metabolites in all the analysed matrices. The most PZQ-burdened tissue was the hepatopancreas, the gill and the skin. In all the samples, the concentration of the drug and its metabolites consistently declined over time. The residue of the parent compound was detected for the longest time in all the tissues. During the study, a significant (P < 0.01) correlation was found within the concentration of PZQ, CPZQ, and TPZQ in the water and all the biological matrices. It was also found that the PZQ residue was not detected below the maximum residue levels (i.e., 20 µg/kg) until 16 days after exposure in the muscle and skin.

Long-term dietary exposure to the non-steroidal anti-inflammatory drugs diclofenac and ibuprofen can affect the physiology of common carp (Cyprinus carpio) on multiple levels, even at "environmentally relevant" concentrations.

The aim of the study was to evaluate the effects of emerging environmental contaminants, the non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac (DCF) and ibuprofen (IBP), on physiological functions in juvenile common carp (Cyprinus carpio). Fish were exposed for 6 weeks, and for the first time, NSAIDs were administered through diet. Either substance was tested at two concentrations, 20 or 2000 µg/kg, resulting in four different treatments (DCF 20, DCF 2000, IBP 20, IBP 2000). The effects on haematological and biochemical profiles, the biomarkers of oxidative stress, and endocrine disruption were studied, and changes in RNA transcription were also monitored to obtain a comprehensive picture of toxicity. Fish exposure to high concentrations of NSAIDs (DCF 2000, IBP 2000) elicited numerous statistically significant changes (p < 0.05) in the endpoints investigated, with DCF being almost always more efficient than IBP. Compared to control fish, a decrease in total leukocyte count attributed to relative lymphopenia was observed. Plasma concentrations of total proteins, ammonia, and thyroxine, and enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase (ALP) were significantly elevated in either group, as were the activities of certain hepatic antioxidant enzymes (superoxide dismutase, glutathione-S-transferase) in the DCF 2000 group. The transcriptomic profile of selected genes in the tissues of exposed fish was affected as well. Significant changes in plasma total proteins, ammonia, ALT, and ALP, as well as in the transcription of genes related to thyroid function and the antioxidant defense of the organism, were found even in fish exposed to the lower DCF concentration (DCF 20). As it was chosen to match DCF concentrations commonly detected in aquatic invertebrates (i.e., the potential feed source of fish), it can be considered "environmentally relevant". Future research is necessary to shed more light on the dietary NSAID toxicity to fish.

Long-term exposure to polycyclic musk tonalide - A potential threat to juvenile zebrafish (Danio rerio)?

Polycyclic musk compounds are commonly used in personal care products to replace expensive natural fragrances. Due to their huge consumption, they have become a part of the aquatic environment. In the present study, a two-month exposure effect of tonalide on juvenile zebrafish (Danio rerio) was investigated. We determined the vitellogenin concentration to define the potential endocrine-disrupting effect of tonalide and also analysed selected indices to evaluate the induction of oxidative stress. The environmentally relevant concentration of tonalide (i.e., 500 ng/l) caused a significant decrease in the catalase activity (P < 0.05) and a significant increase (P < 0.05) in the lipid peroxidation. An increasing lipid peroxidation was also recorded for the highest concentration group tested (i.e., 50 000 ng/l). On the other hand, no significant changes were recorded in vitellogenin in all the exposed groups. Thus, based on these results, we have not demonstrated the endocrine-disrupting activity of tonalide in zebrafish. The results of the oxidative stress indices showed a significant impairment of the antioxidant defence after the two-month tonalide exposure, which could indicate part of the adaptive response to the tonalide toxicity.

Medicine designed to combat diseases of affluence affects the early development of fish. How do plastic microparticles contribute?

The incidence of diseases of affluence, such as diabetes mellitus, cardiovascular diseases, high blood pressure, and high cholesterol has been reported to rise. Consequently, the concentrations of residues of drugs designed to treat these diseases have been rising in water bodies. Moreover, the toxicity of these pharmaceuticals towards fish and other non-target organisms can be even enhanced by microplastic particles that are reportedly present in surface water. Therefore, the aim of this study was to describe the effects of three highly prescribed drugs, in particular metoprolol, enalapril, and metformin on fish early-life stages. Also, it was hypothesized that polystyrene microparticles will increase the toxicity of metoprolol to fish early-life stages. Embryonal acute toxicity tests on Danio rerio and Cyprinus carpio were carried out in order to describe the possible toxic effects of metoprolol, enalapril, and metformin. Also, the acute toxicity of polystyrene microparticles and the combination of metoprolol with polystyrene microparticles were tested on D. rerio embryos. Additionally, a 31-day long embryo-larval subchronic toxicity test was carried out with C. carpio in order to describe the long-term effects of low concentrations of metoprolol. The results of the study show that both metoprolol and enalapril have the potential to disrupt the early development of the heart in the embryonal stages of fish. Also, enalapril and metformin together with polystyrene microparticles seem to possibly disrupt the reproduction cycle and act as endocrine disruptors. Both pure polystyrene microparticles and the combination of them with metoprolol affect inflammatory processes in organisms. Additionally, metformin alters several metabolism pathways in fish early-life stages. The results of the study bring new evidence that even low, environmentally-relevant concentrations of pharmaceuticals have the potential to disrupt the early development of fish, particularly on a molecular level.

Hypoglycin A in Acer genus plants.

Hypoglycin A (HGA) is an amino acid occuring in the Sapindaceae family. Ingestion of certain Acer genus plants belonging to this family has been connected with atypical myopathy (AM) or seasonal pasture myopathy (SPM). To date, all cases of AM/SPM have been associated with sycamore (Acer pseudoplatanus) and boxelder maple (Acer negundo). The aim of this work was to determine and compare HGA in sycamore, boxelder and silver maple (Acer saccharinum), the trees known for HGA content, whose occurence is quite common in the Czech Republic. In sycamore and boxelder maple the effect of location, weather condition and sampling season was evaluated. The other aim was screening for presence of HGA in 12 other species of Acer genus which are grown as ornamental trees in Europe. The determination of HGA was conducted using ultra - high performance liquid chromatography - tandem mass spectrometry (LC/MS). HGA was detected in all samples of sycamore, boxelder and silver maple except for eight leave samples of boxelder maple. In the case of sycamore maple, the highest concentrations of HGA (median) were found in seedlings (770 mg/kg) followed by samaras (130 mg/kg) and by leaves (48 mg/kg) and inflorescences (24 mg/kg). In boxelder maple, significantly higher concentrations of HGA (median) were found in seedlings (550 mg/kg) compared with samaras (45 mg/kg), leaves (14 mg/kg) and inflorescences (24 mg/kg). According to the results the seedlings could pose a significant risk of poisoning, although other factors such as accessibility and palatability of other parts, especially samaras, should be considered. No significant differences of HGA concentrations in silver maple (56 mg/kg) were found between samaras, leaves and inflorescences. HGA was also identified in sugar maple (Acer saccharum), Japanese maple (Acer palmatum), trident maple (Acer buergerianum), paperbark maple (Acer griseum) and Himalayan maple (Acer oblongum). Although silver maple and other ornamental maples have not been reported to cause AM/SPM, the possibility of intoxication in animals can not be excluded.

Pesticides and Parabens Contaminating Aquatic Environment: Acute and Sub-Chronic Toxicity towards Early-Life Stages of Freshwater Fish and Amphibians.

Pesticides and personal care products are two very important groups of contaminants posing a threat to the aquatic environment and the organisms living in it.. Therefore, this study aimed to describe the effects of widely used pesticides and parabens on aquatic non-target biota such as fish (using model organisms Danio rerio and Cyprinus carpio) and amphibians (using model organism Xenopus laevis) using a wide range of endpoints. The first part of the experiment was focused on the embryonal toxicity of three widely used pesticides (metazachlor, prochloraz, and 4-chloro-2-methyl phenoxy acetic acid) and three parabens (methylparaben, propylparaben, and butylparaben) with D. rerio, C. carpio, and X. laevis embryos. An emphasis was placed on using mostly sub-lethal concentrations that are partially relevant to the environmental concentrations of the substances studied. In the second part of the study, an embryo-larval toxicity test with C. carpio was carried out with prochloraz using concentrations 0.1, 1, 10, 100, and 1000 µg/L. The results of both parts of the study show that even the low, environmentally relevant concentrations of the chemicals tested are often able to affect the expression of genes that play either a prominent role in detoxification and sex hormone production or indicate cell stress or, in case of prochloraz, to induce genotoxicity.

Does dietary exposure to 17α-ethinylestradiol alter biomarkers related with endocrine disruption and oxidative stress in the adult triploid of Danio rerio?

This study was conducted to investigate a comprehensive effect of 17α-ethinylestradiol (EE2) in zebrafish (Danio rerio) with the emphasis on endocrine disruption, oxidative stress and detoxification processes at different levels. Adult male triploid zebrafish were exposed to EE2 administered in feed at two concentrations - 10 and 1000 µg/kg for six weeks. The estrogenic potential of EE2 was evaluated using an analysis of vitellogenin, gene expression focused on reproductive disorders and gonad histological examination. The alterations in antioxidant and detoxification status were assessed using analyses of enzyme activities and changes in transcriptional levels of selected genes. The most significant changes were observed especially in fish exposed to a high concentration of EE2 (i.e., 1000 µg/kg). Such high concentration caused extensive mortality (25 %) mainly in the second half of the experiment followed by a highly significant decrease in the length and body weight. Similarly, highly significant induction of vitellogenin level and vtg1 mRNA expression (about 43,000-fold compared to the control) as well as a significant downregulation of gonad aromatase expression (cyp19a1a) and histological changes in testicular tissue were confirmed in this group. In the group exposed to environmentally relevant concentration of EE2 (i.e., 10 µg/kg), no significant differences in vitellogenin were observed, although all fish were positive in the detection of vitellogenin compared to control, where only 40 % of individuals were positive. In addition, the high concentration of EE2 resulted in significant alterations in most monitored antioxidant and detoxifying enzymes with the exception of catalase, followed by strongly significant upregulation in mRNA expression of gsr, gpx1a, cat and cyp1a genes. Furthermore, a significant decrease in the glutathione reductase activity was recorded in fish exposed to 10 µg EE2/kg. To our knowledge, this is the first study which reports the effects of subchronic per oral exposure to EE2 in adult triploid zebrafish.

Use of all-male triploid population of zebrafish (Danio rerio) for evaluation of 17α-ethinylestradiol effects.

OBJECTIVES: We tested the toxicity of ethinylestradiol, a semisynthetic estrogen used in oral contraceptives, on all-male triploid zebrafish using commercial feeds and three different doses concentrations. We aimed to determine whether ethinylestradiol peroral administration resulted in vitellogenin production and whether all-male triploid zebrafish could serve as a model species for xenoestrogen testing. METHODS: The actual concentrations of 17α-ethinylestradiol were 0.0035 (low); 0.0315 (medium) and 0.365 (high) µg/g. Positive control represented commercial feeds containing 0.0465 µg/g of ß-estradiol. The experiment lasted 8 weeks. RESULTS: Our results indicate that 17α-ethinylestradiol consumption does induce vitellogenin production in triploid zebrafish. CONCLUSIONS: The simple presence of vitellogenin is a definite symptom indicative of the potential for such changes due to the action of estrogenic substances. As such, this experiment has shown that the use of all-male triploid zebrafish populations, rather than the mixed-sex populations of other species previously used, could serve as a suitable alternative model population for controlled testing of the effects of xenoestrogens on fish.

Strong energy component is more important than spectral selectivity in modeling responses of midbrain auditory neurons to wide-band environmental sounds.

Modeling central auditory neurons in response to complex sounds not only helps understanding neural processing of speech signals but can also provide insights for biomimetics in neuro-engineering. While modeling responses of midbrain auditory neurons to synthetic tones is rather good, modeling those to environmental sounds is less satisfactory. Environmental sounds typically contain a wide range of frequency components, often with strong and transient energy. These stimulus features have not been examined in the conventional approach of auditory modeling centered on spectral selectivity. To this end, we firstly compared responses to an environmental sound of auditory midbrain neurons across 3 subpopulations of neurons with frequency selectivity in the low, middle and high ranges; secondly, we manipulated the sound energy, both in power and in spectrum, and compared across these subpopulations how their modeled responses were affected. The environmental sound was recorded when a rat was drinking from a feeding bottle (called the 'drinking sound'). The sound spectrum was divided into 20 non-overlapping frequency bands (from 0 to 20 kHz, at 1 kHz width) and presented to an artificial neural model built on a committee machine with parallel spectral inputs to simulate the known tonotopic organization of the auditory system. The model was trained to predict empirical response probability profiles of neurons to the repeated sounds. Results showed that model performance depended more on the strong energy components than on the spectral selectivity. Findings were interpreted to reflect general sensitivity to rapidly changing sound intensities at the auditory midbrain and in the cortex.

Determination of bisphenol A in commercial cat food marketed in the Czech Republic.

OBJECTIVES: Bisphenol A (BPA) is one of the most widely used synthetic compounds on the planet. It is used in the synthesis of polycarbonate plastics, epoxy resins and other polymer materials. Owing to its excellent chemical and physical properties, it is used to produce food and beverage containers or the linings for metal products. BPA has been mentioned as a possible cause of feline hyperthyroidism. Cat food is considered one of the main sources of BPA intake. The purpose of this study was to evaluate BPA concentration in various types of commercial cat food available in the Czech Republic. METHODS: In total, 172 samples prepared from 86 different types of commercial cat food were assessed. The concentration of BPA was measured using liquid chromatography-tandem mass spectrometry. RESULTS: Measurable concentration of BPA was found in all samples (range 0.065-131 ng/g), with the highest concentration (mean ± SD) of BPA in canned food (24.6 ± 34.8 ng/g). When comparing BPA concentration in food trays (1.58 ± 0.974 ng/g), pouches (0.591 ± 0.592 ng/g) and dry food (1.18 ± 0.518 ng/g), concentrations of BPA in food trays and dry food were significantly higher (P <0.01) compared with pouches. Comparing BPA concentrations in canned food of different manufacturers, statistically significant differences were found as well. CONCLUSIONS AND RELEVANCE: The highest concentrations of BPA were found in cans. Thus, cans represent the highest possibility of exposure to BPA in comparison with other types of commercial feline food.

Cystinuria in Dogs and Cats: What Do We Know after Almost 200 Years?

The purpose of this review is to summarize current knowledge on canine and feline cystinuria from available scientific reports. Cystinuria is an inherited metabolic defect characterized by abnormal intestinal and renal amino acid transport in which cystine and the dibasic amino acids ornithine, lysine, and arginine are involved (COLA). At a normal urine pH, ornithine, lysine, and arginine are soluble, but cysteine forms a dimer, cystine, which is relatively insoluble, resulting in crystal precipitation. Mutations in genes coding COLA transporter and the mode of inheritance were identified only in some canine breeds. Cystinuric dogs may form uroliths (mostly in lower urinary tract) which are associated with typical clinical symptoms. The prevalence of cystine urolithiasis is much higher in European countries (up to 14% according to the recent reports) when compared to North America (United States and Canada) where it is approximately 1-3%. Cystinuria may be diagnosed by the detection of cystine urolithiasis, cystine crystalluria, assessment of amino aciduria, or using genetic tests. The management of cystinuria is aimed at urolith removal or dissolution which may be reached by dietary changes or medical treatment. In dogs with androgen-dependent cystinuria, castration will help. In cats, cystinuria occurs less frequently in comparison with dogs.

The biological activity of the organic UV filter ethylhexyl methoxycinnamate in rainbow trout (Oncorhynchus mykiss).

UV filters are able to enter the aquatic environment and negatively affect non-target organisms. The aim of this study was to evaluate subchronic exposure to ethylhexyl methoxycinnamate (EHMC) in rainbow trout. The tested EHMC concentrations of 6.9 (low), 96.0 (medium) and 395.6 µg/kg (high) were used. The lowest concentration was based on environmentally relevant concentrations. The higher concentrations were chosen as a multiple of the lowest one to determine the dose-response relationship. EHMC was incorporated into feed pellets. The experiment was conducted for six weeks in a semi-static system. Haematological, biochemical and oxidative stress indices were determined at the end of the experiment and supplemented by histological examination. Significant changes were proven at medium and high concentrations of EHMC. Specifically, increases of glucose, lactate and decrease of albumin and total protein in plasma indicate a stress ethology. Moreover, a decrease of plasma cholesterol, triacylglycerols and ammonia were observed even in the experimental group exposed to the lowest concentration of EHMC, perceived as an environmentally relevant concentration. The ferric reducing ability of plasma was decreased in all tested concentrations. Exposure to the highest concentration of EHMC resulted in a decrease in leukocyte counts. Increased activity of glutathione peroxidase in liver was recorded for the medium and the highest concentration of EHMC. The level of the thiobarbituric acid reactive substances in kidney was elevated for the highest concentration. Decrease of the activity of glutathione-S-transferase in gills for medium concentration of EHMC was registered. Histopathological examination revealed massive destruction of hepatic parenchyma at the highest concentration of EHMC. All these results support the finding of a stress load on the fish organism. In summary, although subchronic exposure to EHMC had no effect on behaviour, mortality or feed intake, this exposure resulted in the alteration of saccharide, lipid and protein metabolism and weakened antioxidant capacity.

Serum concentration of bisphenol A in elderly cats and its association with clinicopathological findings.

OBJECTIVES: Bisphenol A (BPA) has been mentioned as a possible factor contributing to feline hyperthyroidism. Nevertheless, there are no previous studies reporting on the concentration of BPA in feline serum and its association with thyroid function. The objectives of this study were to measure serum BPA concentration in cats aged ⩾7 years, considered as healthy by their owners, and to compare the results with clinicopathological findings. METHODS: Sixty-nine cats aged ⩾7 years considered as healthy by their owners were enrolled in the study. The concentration of BPA in feline serum was measured using liquid chromatography-tandem mass spectrometry. In all cats, signalment, living environment, diet history, and the results of haematological and biochemical analysis, including thyroxine levels, were available. RESULTS: The mean serum BPA concentration in feline serum was 1.06 ± 0.908 ng/ml. Significant correlation was found between BPA concentration and haemoglobin (r = 0.3397; P = 0.0043), haematocrit (r = 0.3245; P = 0.0065) and the number of red blood cells (r = 0.2916; P = 0.0151), concentration of total protein (r = 0.2383; P = 0.0486), concentration of calcium (r = 0.3915; P = 0.0009) and level of bilirubin (r = 0.3848; P = 0.0011). No other significant correlations were found. Significant differences (P <0.01) were found between mature (1.28 ± 0.994 ng/ml) and geriatric cats (0.420 ± 0.240 ng/ml), between strictly indoor cats (1.27 ± 0.992 ng/ml) and cats with outdoor access (0.660 ± 0.529 ng/ml), and between cats fed canned food (1.23 ± 0.935 ng/ml) and cats fed non-canned food (0.774 ± 0.795 ng/ml). CONCLUSIONS AND RELEVANCE: Measurable serum BPA levels were found in all examined samples. The age of the cats was revealed as a significant factor affecting BPA concentration and mature cats had the highest levels. A significantly higher concentration of BPA was found in cats living strictly indoors and in cats fed canned food. No association was found between BPA and thyroid function. Further studies are needed that focus on hyperthyroid cats for better evaluation of this relationship.

The effect of sulfamethoxazole on oxidative stress indices in zebrafish (Danio rerio).

The aim of this study was to assess the impact of sulfamethoxazole (SMX) on oxidative stress indices in zebrafish (Danio rerio). The test was completed after 14 days. The tested concentrations were 50, 100 and 500 µg/L of SMX. Glutathione peroxidase, glutathione reductase, glutathione S-transferase and lipid peroxidation were investigated to determine the effects of SMX on oxidative stress in zebrafish. Lipid peroxidation gradually increased slightly (but non-significantly) at all tested concentrations during the test as compared to the control. The evaluation of oxidative stress biomarkers showed no significant changes in the activity of antioxidant enzymes in any experimental group exposed to SMX as compared to the control. The gradual increase in lipid peroxidation after 3 and 14 days in the SMX treated groups as compared to the control group indicates increasing cell membrane damage.

The effect of foodborne sertraline on rainbow trout (Oncorhynchus mykiss).

The worldwide consumption of antidepressants is raising as well as their concentrations in the aquatic environment. This increases the risk of food chain contamination and bioaccumulation in aquatic biota. The aim of this study was to describe a potential risk of sertraline as a pollutant from water environment, wherein rainbow trout (Oncorhynchus mykiss) has been chosen as the test organism, because predatory fish are on the top of the food chain in the aquatic environment. The effects of foodborne sertraline were tested on rainbow trout during a 28-day toxicity test according to OECD 215 method. Sertraline was incorporated in commercial feed at a dose of 4.4 µg/kg (environmental concentration), 42 µg/kg and 400 µg/kg. The results confirmed that sertraline has a significant effect on fish behaviour, resulting in suppression of the escape reflex and increased resistance to stress. Moreover, increased Fultons condition factor was found in fish fed with the highest concentration of sertraline. Haematological analysis revealed a statistically significant increase in the number of neutrophilic bands and neutrophil/lymphocyte ratio, and decreased number of lymphocytes. The results of biochemical examination showed a statistically significant decrease in ammonia and lactate concentrations and histological examination revealed changes in gills and caudal kidney. Although sertraline reduces stress in fish, the decline in nonspecific immunity is a risk to fish population stability.

Comprehensive fitness evaluation of common carp (Cyprinus carpio L.) after twelve weeks of atrazine exposure.

Atrazine is frequently detected in surface waters and negatively affect physiological function in aquatic organisms. Even though numerous authors have intensively studied its toxicity, only limited information concerning the long-term fish exposure is available. The aim of this study was evaluation of chronic exposure in common carp. Fish were exposed to a range of atrazine concentrations (0.3 - environmentally relevant concentration; 300; 1000; and 3000 µg/l) for twelve weeks. The potential impact of atrazine exposure was studied using various markers (behaviour; biometrical characteristics; haematological, biochemical and oxidative stress indices and histopathological changes). Most alterations were recorded at the highest concentration (3000 µg/l) which is probably due to a combined effect of both the herbicide exposure and intensive parasite infection development during second week. This group was cancelled after three weeks due to adverse health status, which partly confirmed atrazine immunotoxicity. Chronic exposure resulted in long-term reduction in feed intake followed by a significant decrease in body weight and morphological changes in gill at 1000 µg/l. At the same concentration, significant alterations in haematological (e.g. increase in erythrocyte, leukocyte, lymphocytes and neutrophil counts as well as decrease in monocyte counts) and biochemical (e.g. changes in enzyme activities; increase in glucose; decrease in ammonia) indices were documented, especially during first three weeks. Similar trend, but not so intensive, was observed at 300 µg/l. Moreover, significant changes were observed in various indicators of oxidative stress. These alterations were highly variable with both increasing and decreasing trends depending on dose and analysed tissue. Significant changes, especially in white blood profile, enzyme activities and oxidative stress indices, were proven even at 0.3 µg/l. Obtained results indicate that chronic atrazine exposure of common carp can negatively influence many indicators of health status such as behaviour, immune response, haematological and biochemical profile, oxidative stress indices and organ histopathology.

The effect of the antidepressant venlafaxine on gene expression of biotransformation enzymes in zebrafish (Danio rerio) embryos.

The effect of venlafaxine, a pharmaceutical commonly found in aquatic environment, was analyzed on non-target organism, Danio rerio (Hamilton, 1822). D. rerio embryos were treated by two different concentrations of venlafaxine: either concentration relevant in aquatic environment (0.3 µg/L) or concentration that was two orders of magnitude higher (30 µg/L) for the evaluation of dose-dependent effect. Time-dependent effect was rated at 24, 96, and 144 h post-fertilization (hpf). For gene expression, genes representing one of the phases of xenobiotic biotransformation (0 to III) were selected. The results of this study showed that the effect of venlafaxine on the zebrafish embryos is the most evident at hatching (96 hpf). At this time, the results showed a downregulation of gene expression in each phase of biotransformation and in both tested concentrations. In contrast, an upregulation of most of the genes was observed 144 hpf for both tested venlafaxine concentrations. The study shows that venlafaxine can affect the gene expression of biotransformation enzymes in D. rerio embryos even in the environmentally relevant concentration and thus disrupt the process of biotransformation. Moreover, the pxr regulation of genes seems to be disrupted after venlafaxine exposure in dose- and time-dependent manner.

Functional rate-code models of the auditory brainstem for predicting lateralization and discrimination data of human binaural perception.

This paper presents a rate-code model of binaural interaction inspired by recent neurophysiological findings. The model consists of a peripheral part and a binaural part. The binaural part is composed of models of the medial superior olive (MSO) and the lateral superior olive (LSO), which are parts of the auditory brainstem. The MSO and LSO model outputs are preprocessed in the interaural time difference (ITD) and interaural level difference (ILD) central stages, respectively, which give absolute values of the predicted lateralization at their outputs, allowing a direct comparison with psychophysical data. The predictions obtained with the MSO and LSO models are compared with subjective data on the lateralization of pure tones and narrowband noises, discrimination of the ITD and ILD, and discrimination of the phase warp. The lateralization and discrimination experiments show good agreement with the subjective data. In the case of the phase-warp experiment, the models agree qualitatively with the subjective data. The results demonstrate that rate-code models of MSO and LSO can be used to explain psychophysical data considering lateralization and discrimination based on binaural cues.

Oxidative stress induced by fluoroquinolone enrofloxacin in zebrafish (Danio rerio) can be ameliorated after a prolonged exposure.

The purpose of our experiment was to evaluate the effect of enrofloxacin on biotransformation, oxidative stress and mRNA expression of related genes in fish as a non-target organisms. Zebrafish (Danio rerio) juveniles were treated with enrofloxacin at concentrations of 5, 10 and 500 µg/L for 14 days. A three-day-long test caused changes of catalytic activity of glutathione peroxidase and glutathione-S-transferase. Moreover, lipid peroxidation was observed at the highest concentration. No significant changes either in catalytic activity of antioxidant enzymes or elevated lipid peroxidation were observed from sampling day 7 on. mRNA expression of genes encoding antioxidant enzymes was also not affected by enrofloxacin after a 14-day exposure. This suggests the ability of D. rerio juveniles to adapt to enrofloxacin in a short time period. Moreover, enrofloxacin was not shown to affect collagen, cathepsin K, optic atrophy 1 and pyruvate kinase L/R mRNA expression in this study.

Multibiomarker Responses of Juvenile Stages of Zebrafish (Danio rerio) to Subchronic Exposure to Polycyclic Musk Tonalide.

Synthetic polycyclic musks, widely used as additives in personal care products, are present in both biotic and abiotic matrices of the aquatic environment at concentrations of ng/l to µg/l. Although they are determined at comparatively low concentrations, these levels are biologically relevant and pose a significant growing risk as stressors to aquatic organisms. The purpose of our study was to evaluate the effects of 28-day-long exposure to polycyclic musk tonalide in zebrafish juvenile stages (Danio rerio) using selected biomarkers. Environmentally relevant concentrations of tonalide caused significant changes in selected enzyme activities in the experimental groups exposed to the highest concentrations. The activity of glutathione S-transferase and lipid peroxidation increased significantly (p < 0.05) after exposure to the highest concentration (50,000 ng/l) compared with the control. A similar trend was observed in catalase activity; there was a significant increase (p < 0.05) after exposure to two highest concentrations of tonalide (5000 and 50,000 ng/l). In addition, a statistically significant decrease (p < 0.05) in glutathione reductase activity was found in the lowest test concentration of tonalide (50 ng/l). None of the tested concentrations resulted in histopathological changes in liver, kidney, skin, or gill. Furthermore, no effects on body weight, body length, specific growth rate, and behavior were observed. Our results showed that tonalide exposure induced profound changes in the activities of antioxidant and detoxifying enzymes, such changes representing an adaptive response of the fish organism to tonalide toxicity.