Sphingolipids (SLs) are important signaling molecules and functional components of cellular membranes. Although SLs are known as crucial regulators of neural cell physiology and differentiation, modulations of SLs by environmental neurotoxicants in neural cells and their neuronal progeny have not yet been explored. In this study, we used in vitro models of differentiated neuron-like cells, which were repeatedly exposed during differentiation to model environmental toxicants, and we analyzed changes in sphingolipidome, cellular morphology and gene expression related to SL metabolism or neuronal differentiation. We compared these data with the results obtained in undifferentiated neural cells with progenitor-like features. As model polychlorinated organic pollutants, we used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3'-dichlorobiphenyl (PCB11) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153). PCB153 revealed itself as the most prominent deregulator of SL metabolism and as potent toxicant during early phases of in vitro neurogenesis. TCDD exerted only minor changes in the levels of analysed lipid species, however, it significantly changed the rate of pro-neuronal differentiation and deregulated expression of neuronal markers during neurogenesis. PCB11 acted as a potent disruptor of in vitro neurogenesis, which induced significant alterations in SL metabolism and cellular morphology in both differentiated neuron-like models (differentiated NE4C and NG108-15 cells). We identified ceramide-1-phosphate, lactosylceramides and several glycosphingolipids to be the most sensitive SL species to exposure to polychlorinated pollutants. Additionally, we identified deregulation of several genes related to SL metabolism, which may be explored in future as potential markers of developmental neurotoxicity.

• Klíčová slova
• Ceramide-1-phosphate, Environmental neurotoxicants, Lactosylceramide, Neurogenesis, Sphingolipids,
• MeSH
• buněčná diferenciace účinky léků   MeSH
• buněčné linie MeSH
• látky znečišťující životní prostředí toxicita   MeSH
• neurogeneze účinky léků   MeSH
• neurony účinky léků   metabolismus   MeSH
• neurotoxické syndromy etiologie   genetika   MeSH
• polychlorované bifenyly farmakologie   toxicita   MeSH
• polychlorované dibenzodioxiny toxicita   MeSH
• sfingolipidy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 2,4,5,2',4',5'-hexachlorobiphenyl MeSH Prohlížeč
• 3,3'-dichlorobiphenyl MeSH Prohlížeč
• látky znečišťující životní prostředí MeSH
• polychlorované bifenyly MeSH
• polychlorované dibenzodioxiny MeSH
• sfingolipidy MeSH

The human body gets exposed to a variety of toxins intentionally or unintentionally on a regular basis from sources such as air, water, food, and soil. Certain toxins can be synthetic, while some are biological. The toxins affect the various parts of the body by activating numerous pro-inflammatory markers, like oxidative stresses, that tend to disturb the normal function of the organs ultimately. Nowadays, people use different types of herbal treatments, viz., herbal drinks that contain different spices for detoxification of their bodies. One such example is turmeric, the most commonly available spice in the kitchen and used across all kinds of households. Turmeric contains curcumin, which is a natural polyphenol. Curcumin is a medicinal compound with different biological activities, such as antioxidant, antineoplastic, anti-inflammatory, and antibacterial. Hence, this review gives a comprehensive insight into the promising potential of curcumin in the detoxification of heavy metals, carbon tetrachloride, drugs, alcohol, acrylamide, mycotoxins, nicotine, and plastics. The review encompasses diverse animal-based studies portraying curcumin's role in nullifying the different toxic effects in various organs of the body (especially the liver, kidney, testicles, and brain) by enhancing defensive signaling pathways, improving antioxidant enzyme levels, inhibiting pro-inflammatory markers activities and so on. Furthermore, this review also argues over curcumin's safety assessment for its utilization as a detoxifying agent.

• Klíčová slova
• curcumin, detoxification, health, herbal drugs, in vivo, toxicity,
• MeSH
• akrylamid toxicita   MeSH
• antioxidancia farmakologie   MeSH
• Curcuma chemie   MeSH
• kurkumin * farmakologie   chemie   MeSH
• lidé MeSH
• metabolická inaktivace MeSH
• mykotoxiny toxicita   MeSH
• nikotin MeSH
• oxidační stres účinky léků   MeSH
• těžké kovy toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• akrylamid MeSH
• antioxidancia MeSH
• kurkumin * MeSH
• mykotoxiny MeSH
• nikotin MeSH
• těžké kovy MeSH

Altered gap junctional intercellular communication (GJIC) has been associated with chemical carcinogenesis, where both chemical tumor promoters and chemopreventive agents (CPAs) are known to conversely modulate GJIC. The aim of this study was to investigate whether attenuation of chemically inhibited GJIC represents a common outcome induced by different CPAs, which could be effectively evaluated using in vitro methods. Rat liver epithelial cells WB-F344 were pretreated with a CPA for either 30 min or 24 h, and then exposed to GJIC-inhibiting concentration of a selected tumor promoter or environmental toxicant [12-O-tetradecanoylphorbol-13-acetate (TPA), lindane, fluoranthene, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), perfluorooctanoic acid (PFOA), or pentachlorophenol]. Out of nine CPAs tested, quercetin and silibinin elicited the most pronounced effects, preventing the dysregulation of GJIC by all the GJIC inhibitors, but DDT. Metformin and curcumin attenuated the effects of three GJIC inhibitors, whereas the other CPAs prevented the effects of two (diallyl sulfide, emodin) or one (indole-3-carbinol, thymoquinone) GJIC inhibitor. Significant attenuation of chemically induced inhibition of GJIC was observed in 27 (50%) out of 54 possible combinations of nine CPAs and six GJIC inhibitors. Our data demonstrate that in vitro evaluation of GJIC can be used as an effective screening tool for identification of chemicals with potential chemopreventive activity.

• MeSH
• antikarcinogenní látky farmakologie   MeSH
• DDT toxicita   MeSH
• epitelové buňky účinky léků   MeSH
• fluoreny toxicita   MeSH
• fluorokarbony toxicita   MeSH
• hexachlorcyklohexan toxicita   MeSH
• játra cytologie   účinky léků   MeSH
• kapryláty toxicita   MeSH
• karcinogeny toxicita   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• kurkumin farmakologie   MeSH
• metformin farmakologie   MeSH
• mezerový spoj účinky léků   metabolismus   MeSH
• mezibuněčná komunikace účinky léků   MeSH
• potkani inbrední F344 MeSH
• tetradekanoylforbolacetát toxicita   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikarcinogenní látky MeSH
• DDT MeSH
• fluoranthene MeSH Prohlížeč
• fluoreny MeSH
• fluorokarbony MeSH
• hexachlorcyklohexan MeSH
• kapryláty MeSH
• karcinogeny MeSH
• kurkumin MeSH
• metformin MeSH
• perfluorooctanoic acid MeSH Prohlížeč
• tetradekanoylforbolacetát MeSH

UNLABELLED: Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC. IN CONCLUSION: the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap junction channels are closed by toxicants vary. Thus, accurate assessments of risk posed by toxic agents, and the role of dietary phytochemicals play in preventing or reversing the effects of these agents must take into account the specific mechanisms involved in the cancer process.

• MeSH
• analýza hlavních komponent MeSH
• buněčné linie MeSH
• butadieny farmakologie   MeSH
• fosfatidylcholiny metabolismus   MeSH
• fosfolipasy typu C metabolismus   MeSH
• krysa rodu Rattus MeSH
• mezerový spoj účinky léků   metabolismus   MeSH
• nitrily farmakologie   MeSH
• norbornany MeSH
• potkani inbrední F344 MeSH
• přemostěné cyklické sloučeniny farmakologie   MeSH
• resveratrol MeSH
• stilbeny farmakologie   MeSH
• thiokarbamáty MeSH
• thioketony farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• butadieny MeSH
• fosfatidylcholiny MeSH
• fosfolipasy typu C MeSH
• nitrily MeSH
• norbornany MeSH
• phosphatidylcholine-specific phospholipase C MeSH Prohlížeč
• přemostěné cyklické sloučeniny MeSH
• resveratrol MeSH
• stilbeny MeSH
• thiokarbamáty MeSH
• thioketony MeSH
• tricyclodecane-9-yl-xanthogenate MeSH Prohlížeč
• U 0126 MeSH Prohlížeč

Toxic megacolon belongs to the severe acute complications of inflammatory bowel diseases. The frequency is 1.6-21.4% among patients with ulcerative colitis and 0.3-2% in those with Crohn's disease. The main characteristics of toxic megacolon are toxemia, sepsis and distension of the colon due to the diminished muscular tone, loss of motor activity and increased amount of colonic gas. Sepsis and/or perforation of the large bowel can complicate this situation. The most important diagnostic procedure is the abdominal X-ray. Should the diameter of colonic distension exceed 60 mm, the diagnosis of toxic megacolon has been confirmed. Conservative treatment of toxic megacolon consists of water and electrolyte replacement, total parenteral nutrition, administration of corticosteroids and broad-spectrum antibiotics and repeat patient's prone positioning. If medical therapy is not successful during the first 72 hours, surgical intervention is indicated. The most common procedure is subtotal colonic resection with creation of an ileostomy. Patients with toxic megacolon should be managed at specialised centers, where cooperation of experienced gastroenterologists, surgeons and intensive care experts is possible.

• MeSH
• idiopatické střevní záněty komplikace   MeSH
• lidé MeSH
• toxické megakolon * diagnóza   etiologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The submitted review deals with the diagnosis and treatment of severe forms of toxic colitis from the gastroenterological and surgical aspect. The author emphasizes the importance of early diagnosis of the disease and early onset of conservative treatment which, however, should not exceed 72 hours without obvious improvement of the patient's condition. For surgical intervention the method of choice is subtotal colectomy with ileostomy and a mucous fistula of the rectosigmoid. In cases of early intervention the lethality is less than 10%; when the operation is late (frequently with complications) it is 30% or more. Better information of medical professionals on the disease is desirable.

• MeSH
• kolitida * etiologie   chirurgie   MeSH
• lidé MeSH
• toxické megakolon chirurgie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

This study evaluates the toxic effects of five substances (atropine, fenitrothion, potassium cyanide, mercuric chloride and lead nitrate) on the yeast Saccharomyces cerevisiae. It describes a new biological toxicity test based on inhibition of S. cerevisiae viability and compares it with two standard toxicity tests based on Daphnia magna mobility inhibition (EN ISO 6341) and Vibrio fischeri bioluminiscence inhibition (EN ISO 11348-2). The new biological test -S. cerevisiae lethal test - is cheaper and 24 times faster than the D. magna test. The test speed is comparable with the V. fischeri test but the new test is more sensitive for some substances. The test indicates reliably the presence of all used toxicants in water in concentrations which are significantly lower than the concentration in toxic or lethal doses for man. Therefore, this new toxicity test could be proposed for rapid detection of toxic substances in water.

• MeSH
• atropin analýza   toxicita   MeSH
• chemické látky znečišťující vodu analýza   toxicita   MeSH
• chlorid rtuťnatý analýza   toxicita   MeSH
• dusičnany analýza   toxicita   MeSH
• fenitrotion analýza   toxicita   MeSH
• kyanid draselný analýza   toxicita   MeSH
• methylenová modř metabolismus   MeSH
• monitorování životního prostředí metody   MeSH
• nebezpečné látky analýza   toxicita   MeSH
• olovo analýza   toxicita   MeSH
• Saccharomyces cerevisiae účinky léků   metabolismus   MeSH
• testy toxicity metody   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• atropin MeSH
• chemické látky znečišťující vodu MeSH
• chlorid rtuťnatý MeSH
• dusičnany MeSH
• fenitrotion MeSH
• kyanid draselný MeSH
• lead nitrate MeSH Prohlížeč
• methylenová modř MeSH
• nebezpečné látky MeSH
• olovo MeSH

Caenorhabditis elegans presents functioning, biologically relevant phenotypes and is frequently used as a bioindicator of toxicity. However, most C. elegans in vivo effect-assessment methods are laborious and time consuming. Therefore, we developed a novel method to measure the oxygen consumption rate of C. elegans as a sublethal endpoint of toxicity. This protocol was tested by exposing 50 larval stage one C. elegans individuals for 48 h (at 20 °C) to different concentrations of two toxicants i.e. benzylcetyldimethylammonium chloride (BAC-C16) and cadmium (Cd). Following exposures, the oxygen consumption rate of the C. elegans individuals were measured using the high-throughput functionality of the Seahorse XFe96 Extracellular Flux Analyzer. Dose-response curves for BAC-C16 (R2 = 0.93; P = 0.001) and Cd (R2 = 0.98; P = 0.001) were created. Furthermore, a strong, positive correlation was evidenced between C. elegans oxygen consumption rate and a commonly used, ecologically relevant endpoint of toxicity (growth inhibition) for BAC-C16 (R2 = 0.93; P = 0.0001) and Cd (R2 = 0.91; P = 0.0001). The data presented in this study show that C. elegans oxygen consumption rate can be used as a promising functional measurement of toxicity.

• MeSH
• bezpečnost potravin MeSH
• Caenorhabditis elegans účinky léků   metabolismus   MeSH
• kadmium metabolismus   MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• nebezpečné látky toxicita   MeSH
• průběh práce MeSH
• rychlé screeningové testy metody   normy   MeSH
• Smegmamorpha * MeSH
• spotřeba kyslíku * MeSH
• testy toxicity metody   normy   MeSH
• vystavení vlivu životního prostředí MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kadmium MeSH
• nebezpečné látky MeSH

The use of nanoscaled materials is rapidly increasing, however, their possible ecotoxicological effects are still not precisely known. This work constitutes the first complex study focused on in vivo evaluation of the acute and chronic toxic effects and toxic limits of silver nanoparticles (NPs) on the eukaryotic organism Drosophila melanogaster. For the purpose of this study, silver NPs were prepared in the form of solid dispersion using microencapsulation method, where mannitol was used as an encapsulation agent. This newly prepared solid dispersion with a high concentration of silver NPs was exploited to prepare the standard Drosophila culture medium at a silver concentration range from 10 mg·L(-1) to 100 mg·L(-1) of Ag in the case of the acute toxicity testing and at a concentration equal to 5 mg·L(-1) in the case of the chronic toxicity testing. The acute toxic effect of silver NPs on Drosophila melanogaster was observed for the silver concentration equal to 20 mg·L(-1). At this silver concentration, 50% of the tested flies were unable to leave the pupae, and they did not finish their developmental cycle. Chronic toxicity of silver NPs was assessed by a long-term exposure of overall eight filial generations of Drosophila melanogaster to silver NPs. The long-term exposure to silver NPs influenced the fertility of Drosophila during the first three filial generations, nevertheless the fecundity of flies in subsequent generations consequently increased up to the level of the flies from the control sample due to the adaptability of flies to the silver NPs exposure.

• MeSH
• Drosophila melanogaster účinky léků   MeSH
• fenotyp MeSH
• fertilita účinky léků   MeSH
• kovové nanočástice toxicita   MeSH
• kukla účinky léků   MeSH
• larva účinky léků   MeSH
• stříbro toxicita   MeSH
• testy akutní toxicity MeSH
• testy chronické toxicity MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• stříbro MeSH

OBJECTIVES: The present study aimed to assess the acute effect of cypermethrin on common carp (Cyprinus carpio). Evaluation of toxicity effects of cypermethrin on carp was performed on based assessment of hematological profile, antioxidant and oxidative biomarkers and histopathology. METHODS: For testing of toxicity was used the commercial product Cyperkill 25 EC - CY, which contains 250 g.L-1 of cypermethrin. Carp were exposed to two concentrations (1CY - 4.57 µg.L-1 and 2CY - 45.7 µg.L-1) of CY and a control for 96 hours. RESULTS: Significant reduction (p<0.05) in leukocyte count were in fish exposed to concentration 45.7 µg.L-1 (2CY). The both exposure of CY lead to significant differences (p<0.01) in antioxidants biomarkers (superoxide dismutase, catalase, glutathione reductase, reduced glutathione and glutathione S-transferase) and in lipid peroxidation in carp tissues. Many of these changes were observed in liver, gills, muscle, intestine, brain and kidney. Additionally, exposure to CY caused many histological changes in gills, liver and caudal kidney. CONCLUSION: Exposure to CY caused hematological, biochemical and histopathological changes in carp. This study provides and complements other important results for evaluating the toxicity effect of pyrethroids on fish.

• MeSH
• insekticidy toxicita   MeSH
• kapři metabolismus   MeSH
• pyrethriny toxicita   MeSH
• testy toxicity metody   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cypermethrin MeSH Prohlížeč
• insekticidy MeSH
• pyrethriny MeSH