RESUMO
Staphylococcus aureus, showing the greatest decolorization ability, was further investigated for Methyl Red (MR) Congo Red (CR), Crystal Violet (CV) and Malachite Green (MG) decolorization using response surface methodology (RSM). The chemometric methods use, based on statistical design of experiments (DOEs) such as RSM is becoming increasingly widespread in several sciences such as analytical chemistry, engineering and environmental chemistry. Stapphylococcus aureus ATCC 25923, Stapphylococcus aureus (S1) and Stapphylococcus aureus (S2), were isolated from textile wastewater plant located in KsarHellal, Tunisia and were tested for their decolorization capacity. PCR technique was utilized to identify the 3 bacterial strains and to detect the adhesin gene "cna". Biodegradation of MR, CR, CV and MG (750 ppm), were investigated under shaking condition in Mineral Salt Medium (MSM) solution at pH 7.5 and temperature 30 °C, using a 3.7 × 105 CFU/ml as inoculum size. Our results showed that Staphylococcus aureus had a high decolorization capacity. Nuclear magnetic resonance (NMR) spectroscopy analysis confirmed the biodegradation of dyes. The four dyes mutagenicity with the S9 metabolizing system decreased significantly after biodegradation and totally disappeared. Nuclear magnetic resonance (NMR) spectroscopy analysis confirmed the biodegradation of dyes.
Assuntos
Adesinas Bacterianas/genética , Compostos Azo/toxicidade , Bactérias/genética , Bactérias/metabolismo , Corantes/toxicidade , Mutação , Esgotos/microbiologia , Compostos de Tritil/toxicidade , Compostos Azo/química , Compostos Azo/metabolismo , Aderência Bacteriana/genética , Biodegradação Ambiental , Corantes/química , Corantes/metabolismo , Espectroscopia de Ressonância Magnética , Metabolômica/métodos , Mutagênese/efeitos dos fármacos , Mutagênicos/química , Mutagênicos/metabolismo , Mutagênicos/toxicidade , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Compostos de Tritil/química , Compostos de Tritil/metabolismoRESUMO
CONTEXT: Linalool oxide (OXL) (a monoterpene) is found in the essential oils of certain aromatic plants, or it is derived from linalool. The motivation for this work is the lack of psychopharmacological studies on this substance. OBJECTIVE: To evaluate OXL's acute toxicity, along with its anticonvulsant and antinociceptive activities in male Swiss mice. MATERIAL AND METHODS: OXL (50, 100 and 150 mg/kg, i.p.) was investigated for acute toxicity and in the Rota-rod test. Antinociceptive activity was evaluated by the acetic acid-induced writhing test, and by formalin testing. Anticonvulsant effects were demonstrated by testing for pentylenetetrazol (PTZ)-induced seizures and by Maximum Electroshock headset (MES) test. OXL was administered to the animals intraperitoneally 30 min before for pharmacological tests. RESULTS: OXL showed an LD50 of â¼721 (681-765) mg/kg. In the Rota-rod test, it was observed that OXL caused no damage to the animal's motor coordination. OXL significantly reduced (p < .001) the number of writhings. OXL also significantly decreased (p < .05, p < .01 or p < .001) paw-licking time in the two phases of the formalin test. OXL significantly reduced (p < .01 or p < .001) the duration of tonic seizures in the MES test, and at the dose 150 mg/kg, significantly increased (p < .01) the latency to first seizure in the PTZ test. CONCLUSION: The tested doses of OXL were safe, with no motor impairment, and show clear antinociceptive and anticonvulsant potential. Future investigations with this monoterpene may lead to the development of a new molecule with even higher potency and selectivity.
Assuntos
Analgésicos/farmacologia , Anticonvulsivantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Cicloexanóis/farmacologia , Monoterpenos/farmacologia , Nociceptividade/efeitos dos fármacos , Dor Nociceptiva/prevenção & controle , Convulsões/prevenção & controle , Compostos de Tritil/farmacologia , Ácido Acético , Monoterpenos Acíclicos , Analgésicos/toxicidade , Animais , Anticonvulsivantes/toxicidade , Cicloexanóis/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrochoque , Formaldeído , Dose Letal Mediana , Masculino , Camundongos , Monoterpenos/toxicidade , Atividade Motora , Dor Nociceptiva/induzido quimicamente , Dor Nociceptiva/fisiopatologia , Dor Nociceptiva/psicologia , Pentilenotetrazol , Tempo de Reação/efeitos dos fármacos , Teste de Desempenho do Rota-Rod , Convulsões/induzido quimicamente , Fatores de Tempo , Compostos de Tritil/toxicidadeRESUMO
Although conjugation is well known as an important contributor to color, there is scant recognition concerning involvement of imine and iminium functions in the physiological effects of this class of dyes and pigments. The group includes the dyes methylene blue, rhodamine, malachite green, fuchsin, crystal violet, auramine and cyanins, in addition to the pigments consisting of pyocyanine, phthalocyanine and pheophytin. The physiological effects consist of both toxicity and beneficial aspects. The unifying theme of electron transfer-reactive oxygen species-oxidative stress is used as the rationale in both cases. Toxicity is frequently prevented or alleviated by antioxidants. The apparent dichotomy of methylene blue action as both oxidant and antioxidant is rationalized based on similar previous cases. This mechanistic approach may have practical benefit. This review is important in conveying, for the first time, a unifying mechanism for toxicity based on electron transfer-reactive oxygen species-oxidative stress arising from imine-iminium.
Assuntos
Corantes/toxicidade , Transporte de Elétrons , Iminas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Benzofenoneídio/química , Benzofenoneídio/toxicidade , Corantes/química , Modelos Animais de Doenças , Humanos , Iminas/química , Indóis/química , Indóis/toxicidade , Isoindóis , Azul de Metileno/química , Azul de Metileno/toxicidade , Feofitinas/química , Feofitinas/toxicidade , Piocianina/química , Piocianina/toxicidade , Rodaminas/química , Rodaminas/toxicidade , Corantes de Rosanilina/química , Corantes de Rosanilina/toxicidade , Compostos de Tritil/química , Compostos de Tritil/toxicidadeRESUMO
This article presents the results of a study investigating the biological activity of triphenyltin chloride (TPhT) and two metalloorganic compounds, triphenyllead chloride (TPhL) and triphenylmethane chloride (TPhC), in their interaction with model membranes and the living organisms of fruit flies Drosophila hydei. The study of model membranes (sonicated liposomes) was conducted using the electron spin resonance (ESR) spin probe technique, whereas the experiment on fruit flies involved investigating their viability on media containing the studied compounds. The test results clearly demonstrate that TPhT affects fruit flies more actively than TPhL (complete lethality after 7 days of culture with a TPhT-containing medium). No toxic effect of TPhC on fruit flies was shown. The results of the biological experiment were reflected in the physical experiment involving an ESR study of liposomes: TPhT activity manifested itself as a considerable increase in fluidity of the central region of the liposome lipid bilayer.
Assuntos
Drosophila/efeitos dos fármacos , Lipossomos/química , Compostos Organometálicos/toxicidade , Compostos Orgânicos de Estanho/toxicidade , Compostos de Tritil/toxicidade , Animais , Membrana Celular/efeitos dos fármacos , Drosophila/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Chumbo/química , Modelos Animais , Compostos Organometálicos/química , Compostos Orgânicos de Estanho/química , Estanho/química , Compostos de Tritil/químicaRESUMO
Tris(4-chlorophenyl)methanol (TCPMOH) is a water contaminant with unknown etiology, but is believed to be a byproduct of DDT manufacturing. It is highly persistent in the environment, and bioaccumulates in marine species. TCPMOH has also been measured in human breast milk, which poses a risk for developing infants. However, almost no toxicity data is currently available. In this study, we investigate the hazard posed by developmental TCPMOH exposures using the zebrafish model (Danio rerio). Zebrafish (Danio rerio) embryos were exposed to 0, 0.1, 0.5, 1, or 5 µM TCPMOH beginning at 24 h post fertilization (hpf). Embryonic mortality and incidence of morphological deformities increased in a concentration-dependent manner with TCPMOH exposure. RNA sequencing assessed changes in gene expression associated with acute (4 hour) exposures to 50 nM TCPMOH. Developmental exposure to TCPMOH decreased expression of ahr2, as well as metabolic enzymes cyp1a1, cyp1b1, cyp1c1, cyp1c2, and cyp2y3 (p<0.05). These findings were concordant with decreased Cyp1a1 induction measured by the ethoxyresorufin-O-deethylase (EROD) assay (p<0.05). Pathways associated with xenobiotic metabolism, lipid metabolism, and transcriptional and translational regulation were decreased. Pathways involved in DNA replication and repair, carbohydrate metabolism, and endocrine function were upregulated. Overall, this study demonstrates that TCPMOH is acutely toxic to zebrafish embryos at elevated concentrations.
Assuntos
Compostos de Tritil/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1B1/genética , Ecotoxicologia , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário , Humanos , Inativação Metabólica , Metanol/metabolismo , Ativação Transcricional , Peixe-Zebra/metabolismo , Peixe-Zebra/fisiologia , Proteínas de Peixe-Zebra/genéticaRESUMO
Rhizobium radiobacter MTCC 8161 completely decolorized methyl violet (10 mg l(-1)) within 8 h both at static and shaking conditions. The decolorization time increased with increasing dye concentration. The effect of different carbon and nitrogen sources on the decolorization of methyl violet was studied. The maximum decolorization was observed in the presence of sucrose (1%) and urea (1%). UV-Visible, HPLC and FTIR analysis of extracted products confirmed biodegradation of methyl violet. The significant increase in the activities of lignin peroxidase and aminopyrine N-demethylase in the cells obtained after decolorization indicated involvement of these enzymes in the decolorization process. In addition to methyl violet, this strain also shows an ability to decolorize various industrial dyes, (red HE7B, yellow 4G, blue 2B, navy blue HE22, red M5B and red HE3B).
Assuntos
Agrobacterium tumefaciens/metabolismo , Corantes/metabolismo , Violeta Genciana/metabolismo , Compostos de Tritil/metabolismo , Aminopirina N-Desmetilase/metabolismo , Biodegradação Ambiental , Cromatografia Líquida de Alta Pressão , Cor , Corantes/toxicidade , Violeta Genciana/toxicidade , Peroxidases/metabolismo , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Sacarose/metabolismo , Têxteis , Testes de Toxicidade , Compostos de Tritil/toxicidade , Ureia/metabolismoRESUMO
Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies.
Assuntos
Oximetria/métodos , Oxigênio/análise , Compostos de Tritil/química , Alanina Transaminase/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Espectroscopia de Ressonância de Spin Eletrônica , Corantes Fluorescentes/química , Corantes Fluorescentes/toxicidade , Radicais Livres/química , Células HT29 , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Soluções/química , Testes de Toxicidade Aguda , Transaminases/metabolismo , Compostos de Tritil/síntese química , Compostos de Tritil/toxicidadeRESUMO
To elucidate the comparative susceptibility of newborn rats to chemicals, newborn and young animals were administered six industrial chemicals by gavage from postnatal days (PND) 4 to 21, and for 28 days starting at 5-6 weeks of age respectively, under the same experimental conditions as far as possible. As two new toxicity endpoints specific to this comparative analysis, presumed no-observed-adverse-effect-levels (pNOAELs) were estimated based on results of both main and dose-finding studies, and presumed unequivocally toxic levels (pUETLs) were also decided. pNOAELs for newborn and young rats were 40 and 200 for 2-chlorophenol, 100 and 100 for 4-chlorophenol, 30 and 100 for p-(alpha,alpha-dimethylbenzyl) phenol, 100 and 40 for (hydroxyphenyl)methyl phenol, 60 and 12 for trityl chloride, and 100 and 300 mg/kg/day for 1,3,5-trihydroxybenezene, respectively. To determine pUETLs, dose ranges were adopted in several cases because of the limited results of experimental doses. Values for newborn and young rats were thus estimated as 200-250 and 1000 for 2-chlorophenol, 300 and 500 for 4-chlorophenol, 300 and 700-800 for p-(alpha,alpha-dimethylbenzyl) phenol, 140-160 and 1000 for (hydroxyphenyl)methyl phenol, 400-500 and 300 for trityl chloride, and 500 and 1000 mg/kg/day for 1,3,5-trihydroxybenzene, respectively. In most cases, newborn rats were 2-5 times more susceptible than young rats in terms of both the pNOAEL and the pUETL. An exception was that young rats were clearly more susceptible than their newborn counterparts for trityl chloride.
Assuntos
Derivados de Benzeno/toxicidade , Nitrofenóis/toxicidade , Fenóis/toxicidade , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Clorofenóis/toxicidade , Relação Dose-Resposta a Droga , Feminino , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estômago/efeitos dos fármacos , Compostos de Tritil/toxicidadeRESUMO
The influence of tris(4-chlorophenyl)methanol (TCPM) and dichlorodiphenyltrichloroethane (o,p'DDT) on forskolin induced cAMP signalling in single adherent bovine oviductal cells was investigated. An increase in the intracellular cAMP levels was measured indirectly by an increase in the 520/580 nm fluorescence emission ratio of the protein kinase A fluorosensor (FICRhR). FICRhR was microinjected into single cells, and the 520/580 nm fluorescence emission ratio was monitored by image cytometry with an image analysis system as a measure of intracellular cAMP concentration ([cAMP](i)). Applications of dibutyryl cAMP and forskolin caused time- and dose-dependent effects on [cAMP](i) in single oviductal cells. The addition of 16 or 32 microM TCPM or DDT for 1 h to the culture medium decreased the intracellular cAMP concentration significantly, whereas 8 microM was not able to influence the [cAMP](i). In the presence of both pesticides at 16 microM the forskolin (30 microM)-induced [cAMP](i) was significantly reduced after 1 h of incubation. It is suggested that TCPM can have the same influence compared with DDT on cells responsible for reproduction.
Assuntos
Colforsina/farmacologia , AMP Cíclico/metabolismo , DDT/toxicidade , Estrogênios não Esteroides/toxicidade , Inseticidas/toxicidade , Oviductos/citologia , Compostos de Tritil/toxicidade , Animais , Bovinos , Técnicas de Cultura de Células , Feminino , Transdução de SinaisRESUMO
Tris(4-chlorophenyl)methanol (TCPM) is a by-product in the manufacture of technical grade DDT, which is known to alter properties and functions of the female reproductive system. We investigated whether in vitro TCPM has an influence on the function of gap junction-mediated intercellular communication (GJIC) and gap junction protein expression of connexin 43 (Cx43) in cultured bovine granulosa cells. GJIC was assessed by fluorescent dye microinjection (dye-coupling). After a 1-h exposure to TCPM at a concentration of 32 microM, a significant (P<0.05) reduction in dye coupling occurred. The same result was obtained with o,p'-DDT. At a concentration of 32 microM both pesticides were cytotoxic as indicated by significant (P<0.05) increased propidium iodide staining of the cell nuclei. Little or no effect on the stainable pattern of connexons occurred after 1 h incubation time, while after 3 h treatment from 16 to 64 microM TCPM, a significant inhibition in the immunostaining resulted and the concentrations of 32 and 64 microM TCPM were cytotoxic for the granulosa cells. The freeze-fracture electron microscopy resulted in small differences in the morphology of gap junction plaques of cell cultures treated for 3 h with 8 or 16 microM TCPM in comparison to untreated cells. After treatment with 32 microM TCPM, gap junction plaques were very rarely detected and the lateral intramembraneous particles (IMP) distribution of many plasma membranes was strongly altered. Estimation of the cellular parameters may lead to an enhanced understanding of the mechanism of chemically induced toxicity by TCPM, that causes a general toxic effect on granulosa cells. We can conclude that TCPM is a toxic risk in the same manner as DDT.
Assuntos
Comunicação Celular/efeitos dos fármacos , Junções Comunicantes/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Compostos de Tritil/toxicidade , Animais , Bovinos , Nucléolo Celular/efeitos dos fármacos , Nucléolo Celular/metabolismo , Nucléolo Celular/ultraestrutura , Células Cultivadas , Conexina 43/metabolismo , DDT/toxicidade , Relação Dose-Resposta a Droga , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Técnica de Fratura por Congelamento , Junções Comunicantes/ultraestrutura , Células da Granulosa/citologia , Células da Granulosa/metabolismo , Processamento de Imagem Assistida por Computador , Inseticidas/farmacologiaRESUMO
Polarographic reduction of some triphenylmethane dyes in strictly anhydrous solutions was studied in the absence and presence of alpha-lipoic acid. The values of the half-wave potentials E1/2 and the parameter of potential carcinogenicity tg alpha were determined for all compounds studied. The current value of the first diffuse polarographic wave was increased in the presence of alpha-lipoic acid for all of the compounds. The increase was linear and depended on the alpha-lipoic acid concentration in anhydrous solutions. The highest determined value of tg alpha belonged to crystal violet (0.420) and to methyl violet 2B (0.440). The values indicate potential carcinogenic activities of the respective triphenylmethane dyes.
Assuntos
Carcinógenos/química , Carcinógenos/toxicidade , Corantes/química , Corantes/toxicidade , Compostos de Tritil/química , Compostos de Tritil/toxicidade , Eletroquímica , Oxirredução , Polarografia/métodos , Ácido Tióctico/químicaRESUMO
Biodegradation of triphenylmethane dyes by bacteria, actinomycetes, yeasts, and fungi are discussed in detail. The disadvantages of physical and chemical treatment processes of dye wastewater are also discussed. Biological treatment processes have many advantages over the chemical and physical treatment processes such as possibility of degradation of dye molecules to carbon dioxide and water and formation of less sludge in addition to being environmentally friendly. This group of dyes is toxic depending on the concentration used. Toxicity of triphenylmethane dyes is discussed with respect to different organisms. Some aspects of biodegradative products of this group of dyes are also mentioned.
Assuntos
Biodegradação Ambiental , Corantes/metabolismo , Compostos de Tritil/metabolismo , Bactérias/metabolismo , Fungos/metabolismo , Violeta Genciana/metabolismo , Violeta Genciana/toxicidade , Estrutura Molecular , Compostos de Tritil/toxicidade , Poluentes da Água/metabolismoRESUMO
Tris(4-chlorophenyl)methanol (TCPM) is a global contaminant of unknown origin that is structurally related to the endocrine modulating pesticides 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and Dicofol. Therefore, the potential reproductive toxic effects of TCPM were investigated in sexually mature male Sprague Dawley rats (n = 20) treated with 1.0, 10.0 or 100 ppm of TCPM mixed in the diet for 28 days. The calculated TCPM intake was 0.0, 0.1, 1.2 and 12.4 mg/kg/day, respectively. Serum concentrations of follicle stimulating hormone (FSH) in terminal blood samples were significantly (P < 0.02) elevated in the highest dose group compared to the controls. In contrast, dietary exposure to TCPM had no effect on circulating levels of luteinizing hormone (LH), testosterone (T) and the T/LH ratio. Incubation of MCF-7 cells with increasing concentrations of TCPM failed to either induce proliferation or to block the proliferative effect induced by estradiol indicating that TCPM is neither estrogenic or anti-estrogenic. Relative binding affinity studies using androgen receptors from the prostate revealed that TCPM has a binding affinity comparable to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), the principle metabolite of DDT. In addition, the calculated Ki (0.62 microM) for TCPM is lower than the reported Ki's for the antiandrogenic pesticides p,p'-DDE and vinclozolin. Although TCPM binds with the androgen receptor in vitro, the absence of both an effect on serum T levels and morphological changes in the testis suggests that the mechanism of action for elevated FSH levels seen in vivo may not involve an antiandrogenic effect of TCPM at the dose level used in this study. The no adverse effect level for reproductive effects of TCPM is 10 ppm which is equivalent to a calculated intake of 1.2 mg/kg/day.
Assuntos
Poluentes Ambientais/toxicidade , Reprodução/efeitos dos fármacos , Compostos de Tritil/toxicidade , Animais , Apoptose , Divisão Celular/efeitos dos fármacos , DDT/metabolismo , Epididimo/efeitos dos fármacos , Epididimo/patologia , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Masculino , Próstata/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/metabolismo , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue , Compostos de Tritil/metabolismo , Células Tumorais CultivadasRESUMO
The systemic toxicity of tris(4-chlorophenyl)methanol (TCPM) was studied in male and female rats following 4 weeks dietary exposure dosed at 1, 10 and 100 ppm. An increased spleen to body weight ratio was observed in males at 10 and 100 ppm and in females at 100 ppm. An increased liver to body weight ratio was detected in both sexes at 100 ppm. Dose-related increases in hepatic Phase-I (AH, APDM, EROD and PROD) and Phase-II (UDPGT, GST) enzyme activities were observed generally at 10 and 100 ppm, with the elevation in PROD activity being the most marked. Increased urinary ascorbic acid was detected in both males and females after 1 week of treatment at 100 ppm and after 4 weeks of treatment at 10 and 100 ppm. At 10 and 100 ppm, elevated % lymphocytes were found in males, and higher white blood cell and lymphocyte counts were observed in females. In the liver, mild to moderate cytoplasmic changes consistent with proliferation of smooth endoplasmic reticulum were present in rats of both sexes at 10 and 100 ppm, and increased number of hepatocytes undergoing apoptosis were observed in male rats at 100 ppm. Mild splenic changes consisting of sinus hyperplasia in males and females at 100 ppm and mantle zone atrophy in males at 100 ppm were also observed. It was concluded that TCPM at a dietary concentration of 10 ppm (equivalent to 1.2 mg/kg/day) produced systemic changes in rats that included various hepatic effects, increased splenic weight, and modulations in white blood cells and lymphocyte counts.
Assuntos
Peso Corporal/efeitos dos fármacos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Baço/efeitos dos fármacos , Compostos de Tritil/toxicidade , Administração Oral , Análise de Variância , Animais , Ácido Ascórbico/urina , Sistema Enzimático do Citocromo P-450/metabolismo , Citoplasma/efeitos dos fármacos , Relação Dose-Resposta a Droga , Retículo Endoplasmático Liso/efeitos dos fármacos , Feminino , Isoenzimas/metabolismo , Rim/patologia , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Contagem de Linfócitos/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Baço/patologia , Compostos de Tritil/administração & dosagemRESUMO
Electron paramagnetic resonance imaging (EPRI) can be used to noninvasively and quantitatively obtain three-dimensional maps of tumor pO2. The paramagnetic tracer triarylmethyl (TAM), a substituted trityl radical moiety, is not toxic to animals and provides narrow isotropic spectra, which is ideal for in vivo EPR imaging experiments. From the oxygen-induced spectral broadening of TAM, pO2 maps can be derived using EPRI. The instrumentation consists of an EPRI spectrometer and 7T magnetic resonance imaging (MRI) system both operating at a common radiofrequency of 300 MHz. Anatomic images obtained by MRI can be overlaid with pO2 maps obtained from EPRI. With imaging times of less than 3 min, it was possible to monitor the dynamics of oxygen changes in tumor and distinguish chronically hypoxic regions from acutely hypoxic regions. In this article, the principles of pO2 imaging with EPR and some relevant examples of tumor imaging are reviewed.
Assuntos
Hipóxia Celular , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Neoplasias/patologia , Animais , Benzoatos/toxicidade , Espectroscopia de Ressonância de Spin Eletrônica/instrumentação , Glicólise , Compostos Heterocíclicos com 3 Anéis/toxicidade , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Imageamento por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética/métodos , Camundongos , Modelos Biológicos , Proteínas de Neoplasias/fisiologia , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Neoplasias/radioterapia , Neoplasias Experimentais/irrigação sanguínea , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Experimentais/radioterapia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/fisiopatologia , Ressonância Magnética Nuclear Biomolecular/instrumentação , Ressonância Magnética Nuclear Biomolecular/métodos , Oxigênio/análise , Pressão Parcial , Tolerância a Radiação , Marcadores de Spin , Compostos de Tritil/toxicidade , Microambiente TumoralAssuntos
Corantes de Alimentos/toxicidade , Animais , Antraquinonas/toxicidade , Compostos Azo/toxicidade , Carotenoides/toxicidade , Cães , Feminino , Aditivos Alimentares/toxicidade , Humanos , Índigo Carmim/toxicidade , Metais/toxicidade , Camundongos , Óxidos/toxicidade , Pigmentos Biológicos/toxicidade , Gravidez , Coelhos , Ratos , Compostos de Tritil/toxicidade , Xantenos/toxicidadeRESUMO
Sickle cell disease (SCD) is characterized by hemolytic as well as vaso-occlusive complications. The development of treatments for this inherited disease is based on an understanding of its pathophysiology. Polymerization of sickle hemoglobin is dependent on several independent factors, including the intracellular hemoglobin concentration. The hydration state (and intracellular hemoglobin concentration) of the sickle erythrocyte depends on the loss of solute and osmotically obliged water through specific pathways. Senicapoc (also known as ICA-17043) is a potent blocker of the Gardos channel, a calcium-activated potassium channel of intermediate conductance, in the red blood cell. Preclinical studies and studies in transgenic models of SCD show that inhibition of potassium efflux through the Gardos channel is associated with an increased hemoglobin level, decreased dense cells and decreased hemolysis. Senicapoc is well tolerated when administered to SCD patients and produces dose-dependent increases in hemoglobin and decreases in markers of hemolysis. Despite the lack of a reduction in the frequency of pain episodes, the increasing recognition that hemolysis contributes to the development of several SCD-related complications suggests that by decreasing hemolysis, senicapoc may yet prove to be beneficial in this disease.
Assuntos
Acetamidas/uso terapêutico , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Hemólise/efeitos dos fármacos , Compostos de Tritil/uso terapêutico , Acetamidas/efeitos adversos , Acetamidas/química , Acetamidas/toxicidade , Anemia Falciforme/complicações , Anemia Falciforme/fisiopatologia , Animais , Animais Geneticamente Modificados , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Camundongos , Compostos de Tritil/efeitos adversos , Compostos de Tritil/química , Compostos de Tritil/toxicidadeRESUMO
We comprehensively re-analyzed the toxicity data for 18 industrial chemicals from repeated oral exposures in newborn and young rats, which were previously published. Two new toxicity endpoints specific to this comparative analysis were identified, the first, the presumed no observed adverse effect level (pNOAEL) was estimated based on results of both main and dose-finding studies, and the second, the presumed unequivocally toxic level (pUETL) was defined as a clear toxic dose giving similar severity in both newborn and young rats. Based on the analyses of both pNOAEL and pUETL ratios between the different ages, newborn rats demonstrated greater susceptibility (at most 8-fold) to nearly two thirds of these 18 chemicals (mostly phenolic substances), and less or nearly equal sensitivity to the other chemicals. Exceptionally one chemical only showed toxicity in newborn rats. In addition, Benchmark Dose Lower Bound (BMDL) estimates were calculated as an alternative endpoint. Most BMDLs were comparable to their corresponding pNOAELs and the overall correlation coefficient was 0.904. We discussed how our results can be incorporated into chemical risk assessment approaches to protect pediatric health from direct oral exposure to chemicals.
Assuntos
Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Fatores Etários , Animais , Animais Recém-Nascidos , Derivados de Benzeno/toxicidade , Humanos , Nível de Efeito Adverso não Observado , Fenóis/toxicidade , Ratos , Ratos Sprague-Dawley , Medição de Risco , Compostos de Tritil/toxicidadeRESUMO
In recent years, there has been growing concern that environmental pollutants in general, and organochlorines in particular, adversely affect male fertility. Therefore, we investigated the effects of tris(4-chlorophenyl)methanol (TCPM), non-ortho PCB 77 and gamma-hexachlorocyclohexane (gamma-HCH, lindane) on human sperm functions in vitro. Human spermatozoa from healthy donors were washed in human tubular fluid medium containing 1% human serum albumin, filtered through glass wool and exposed to different concentrations of TCPM, PCB 77 or gamma-HCH. After incubation for 5 h at 37 degrees C and 5% CO(2), sperm vitality and the percentage of living acrosome-reacted spermatozoa were examined using triple stain technique. Total sperm motility was evaluated by computer-assisted sperm analysis (Stroemberg-Mika) after 5 h. For TCPM, total motility was additionally measured after 18 and 40 h. Different concentrations of PCB 77 and gamma-HCH did not alter the percentage of spontaneous living acrosome-reacted spermatozoa, vitality and total motility. TCPM dose-dependently altered sperm motility, vitality and acrosome reaction. The percentage of living acrosome-reacted spermatozoa was increased at overtly toxic concentrations. Therefore, it is suggested that unspecific acrosomal loss has been induced by degenerative processes. In conclusion, even high concentrations of PCB 77 and gamma-HCH did not affect human sperm functions in vitro. Only very high cytotoxic TCPM concentrations modulated spontaneous acrosome reaction and total motility. Therefore, in vivo effects on human sperm function seem to be unlikely. However, individual susceptibility has to be considered and little is known about additive and possible synergistic effects as other environmental pollutants with similar potencies have been found in the human male and female reproductive tract.
Assuntos
Reação Acrossômica/efeitos dos fármacos , Hexaclorocicloexano/toxicidade , Bifenilos Policlorados/toxicidade , Espermatozoides/efeitos dos fármacos , Compostos de Tritil/toxicidade , Meios de Cultura , Disruptores Endócrinos/toxicidade , Humanos , Técnicas In Vitro , Masculino , Bifenilos Policlorados/análise , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologiaRESUMO
In this study we investigated the effects of a series of phosphonium salts and phosphoranes on the catalytic activity of acetylcholinesterase and on the viability of the various life stages of Schistosoma mansoni worms. All the tested compounds showed an inhibitory effect towards the S. mansoni acetylcholinesterase (AChE) activity. The most effective compound, p-xylylene bis(triphenylphosphonium) dibromide (No. 16) displayed approximately 100% inhibition at concentration of 10(-5)-10(-6)M. No significant difference was found in the sensitivity of the enzyme obtained from the various stages of the parasite life cycle to the effect of the drugs. Each compound was also tested for its toxicity towards 3 h old schistosomula and 7-9 week adult worms under in vitro culture conditions. In the case of the larvae, after 2 days in culture, only three compounds (Nos. 4, 11 and 12) out of sixteen tested exhibited efficient killing of the schistosomula while the others had a very slight toxic activity or no toxicity at all. On the other hand, all the compounds showed a significant toxicity towards the adult worms and the most effective one, allytriphenylphosphonium bromide (No. 11), retained its toxic effect even at an extremely high dilution (10(-8)M). However, the cumulative results in this paper do not demonstrate a significant correlation between the inhibitory effect of the phosphonium salts and phosphoranes on the AChE activity of the schistosomes and their toxicity towards the worms. The LD50 value (i.v.) of the compound which showed the highest toxic effect in vitro (No. 11) was found to be 30 +/- 1.7 mg/kg in mice.(ABSTRACT TRUNCATED AT 250 WORDS)