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1.
Ecotoxicology ; 30(4): 751-755, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33770306

RESUMO

Regeneration is a widely spread process across the animal kingdom, including many species of marine crustaceans. It is strongly linked to hormonal cycles and, therefore, a great endpoint candidate for toxicology studies. We selected the amphipod Parhyale hawaiensis as test organism, already used in ecotoxicological studies and able to regenerate its body appendages. We are proposing a protocol to use the antenna regeneration as a toxicity endpoint. First, we evaluated differences in time of completion of regeneration in males and females after the amputation of one antenna of 6 months old animals. Then we compared the influence of different testing volumes in the regeneration process (100 and 5 mL). We used as testing substances, dimethyl sulfoxide (DMSO) and diflubenzuron, a chitin synthesis inhibitor. The most suitable protocol consisted of volumes of 5 mL in 12-well microplates, with 1 organism per well, 12 organisms per concentration (1:1 females/males) and test time duration of around 5 weeks. DMSO accelerated regeneration time with a NOEC of 0.06%. Diflubenzuron inhibited the time necessary to its completion with a NOEC of 0.32 µg L-1. We conclude that the Parhyale hawaiensis antenna regeneration protocol proposed here is a potential tool in ecotoxicology, but more studies are required for its validation not only to verify its utility for testing chemicals but also environmental samples.


Assuntos
Anfípodes , Diflubenzuron , Animais , Dimetil Sulfóxido/toxicidade , Ecotoxicologia , Feminino , Masculino
2.
Exp Parasitol ; 224: 108103, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33771537

RESUMO

In this work the effect of (-)-epicatechin on the development of amebic liver abscess in hamsters was evaluated. (-)-epicatechin is a flavonoid present in plants that possesses various biological properties, including its activity against some protozoal parasites; however its antiamebic activity in a living model had not been evaluated. Syrian golden hamsters were intrahepatically inoculated with 1x106E. histolytica trophozoites, three days after inoculation they received nine intraperitoneal doses of (-)-epicatechin (10 mg/100 g) every 48 h. Animals without treatments and treated with metronidazole were included as controls. Macroscopic characteristics of the hepatic abscess, histopathological analysis of the tissue and the levels of inflammatory cytokines were determined. (-)-epicatechin produced a decrease in liver abscess progression being observed only 9.49% of damage compared to 84% shown by untreated animals. During treatment with (-)-epicatechin hepatic tissue showed signs of liver repair and absence of amoebae. Additionally, (-)-epicatechin produced a modulating effect on inflammatory cytokines TNF-α, IL-1ß and IL-10. All these events observed in animals treated with (-)-epicatechin could contribute to the elimination of trophozoites and liver healing.


Assuntos
Catequina/uso terapêutico , Abscesso Hepático Amebiano/prevenção & controle , Análise de Variância , Animais , Antiprotozoários/uso terapêutico , Antiprotozoários/toxicidade , Catequina/toxicidade , Cricetinae , Citocinas/análise , Citocinas/metabolismo , Dimetil Sulfóxido/toxicidade , Modelos Animais de Doenças , Fígado/imunologia , Abscesso Hepático Amebiano/tratamento farmacológico , Masculino , Mesocricetus , Metronidazol/uso terapêutico , Metronidazol/toxicidade , Reação em Cadeia da Polimerase em Tempo Real
3.
Chemosphere ; 270: 129405, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33412354

RESUMO

Dimethyl sulfoxide (DMSO) is produced in nature and is known to be a source of carbon and sulfur for marine microorganisms. It is currently used in many biological experiments, pharmaceutical preparations, and energy-producing systems such as lithium batteries. Therefore, the toxicity of DMSO has been studied because of its various implications to living organisms; however, such studies are largely limited to measuring individual toxicity whereas the combined toxicity of DMSO with other compounds has rarely been investigated. In the present study, the combined acute toxicity of 0.1% and 0.5% DMSO with vanadium was investigated in zebrafish embryos; the LC50 values of these combinations were 62.0 and 6.38 ppm, respectively. In individual toxicity tests, neither DMSO nor vanadium caused such mortality levels. Therefore, both 0.1% and 0.5% DMSO had a synergistic effect with vanadium, and this result was confirmed using an independent action model. This combined toxicity delayed the development of zebrafish embryos and caused pericardial edema. The synergistic effect of DMSO and vanadium was found to be related to reduced pH and inhibition of cytochrome c oxidase activity. Given its potential synergistic toxicity to aquatic organisms, the introduction of DMSO into the environment should be investigated and routinely monitored.


Assuntos
Dimetil Sulfóxido , Peixe-Zebra , Animais , Dimetil Sulfóxido/toxicidade , Embrião não Mamífero , Testes de Toxicidade , Vanádio/toxicidade
4.
Eur J Oral Sci ; 129(1): e12756, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33511712

RESUMO

This study evaluated the cytotoxicity of methacrylate-based resins containing dimethyl sulfoxide (DMSO). DMSO was incorporated into hydrophobic (R2) and hydrophilic (R5) resins at weight concentrations of 0, 0.01, 0.1, 1, 5, or 10 w/w %. Resin discs (n = 10/group) were prepared. Human gingival fibroblasts (HGF-1) were exposed to resin eluates for 24 h. Furthermore, dentin barrier test was performed using 3-D cultures of odontoblast-like cells (SV40 transfected pulp derived cells) with dentin slices of 400 µm thickness (n = 8). After acid etching of dentin, DMSO-modified resins were applied into the cavity part of the device and light-cured for 20 s. Cell viability (%) was assessed by MTT and analyzed spectrometrically. Data were analyzed by ANOVA and Tukey test (α = 0.05). Resin eluates showed statistically significantly lower % cell viability for all neat and DMSO-modified resins than seen for the negative control. Moreover, DMSO-R5 eluates resulted in significantly lower % cell viability than DMSO-R2 emulates. The dentin barrier test showed that DMSO-R2 did not result in significantly lower % cell viability, whereas incorporation of 1-10 w/w % DMSO into R5 resulted in significantly lower % of cell viability. Incorporating DMSO into hydrophilic self-etching resins may increase cytotoxicity. The biocompatibility is not influenced by the addition of DMSO into hydrophobic resin.


Assuntos
Colagem Dentária , Dimetil Sulfóxido , Resinas Compostas , Cimentos Dentários , Dentina , Adesivos Dentinários , Dimetil Sulfóxido/toxicidade , Humanos , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Metacrilatos/toxicidade , Cimentos de Resina/toxicidade
5.
Am J Physiol Gastrointest Liver Physiol ; 319(2): G121-G132, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32567324

RESUMO

Nongenomic glucocorticoid (GC) and serum- and glucocorticoid-inducible kinase 1 (SGK1) signaling regulate ion transport, but CFTR has not been investigated in the intestine. We examined GC, SGK1, and phosphatidylinositol 3-kinase (PI3K) kinase signaling of CFTR ion transport in native intestine and the role of GCs on mRNA, protein, surface expression, and cyclic guanosine monophosphate (cGMP)-elicited diarrhea. Rats were treated with dexamethasone (DEXA; 2 mg/kg ip) or DMSO for 1, 4, and 24 h. Cyclic adenosine monophosphate (cAMP)-activated ion transport was examined in the presence or absence of SGK1 and PI3K inhibitors. Phosphorylation of SGK1, phosphoinositide-dependent kinase 1, and Akt kinases was confirmed by immunoblots using phosphor-specific antibodies. Tissue lysates were analyzed by mass spectrometry. CFTR and SGK1 mRNA were measured by quantitative PCR. Changes in total and surface CFTR protein were determined. The role of GC in cGMP-activated CFTR ion transport was examined. GC synergistically increased CFTR ion transport by SGK1 and PI3K signaling and increased CFTR protein without altering SGK1 or CFTR mRNA. GC induced highest levels of CFTR protein at 4 h that were associated with marked increase in surface CFTR, phosphorylation of the ubiquitin ligase neural precursor cell expressed developmentally downregulated 4-like (Nedd4-2), and 14-3-3ε, supporting their roles in surface retention and stability. Coimmunoprecipitation of CFTR, Nedd4-2, and 14-3-3ε indicated that assembly of this complex is a likely effector of the SGK and Akt pathways. Mass spectrometry identified phosphorylated peptides in relevant proteins. GC-SGK1 potently regulates CFTR in the intestine and is implicated in diarrheal disease.NEW & NOTEWORTHY This is the first study to examine the mechanisms of glucocorticoid, serum- and glucocorticoid-inducible kinase 1, and nongenomic kinase signaling of CFTR in the native intestine. We identified unique and druggable intestine-specific factors of the pathway that are targets for treating stress-induced diarrhea.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Dexametasona/toxicidade , Diarreia/etiologia , Dimetil Sulfóxido/toxicidade , Proteínas Imediatamente Precoces/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Animais , Toxinas Bacterianas/toxicidade , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Diarreia/induzido quimicamente , Enterotoxinas/toxicidade , Proteínas de Escherichia coli/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Imediatamente Precoces/genética , Masculino , Ubiquitina-Proteína Ligases Nedd4/genética , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Transporte Proteico , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , /metabolismo , Ratos , Ratos Sprague-Dawley , Trocador 3 de Sódio-Hidrogênio/genética , Trocador 3 de Sódio-Hidrogênio/metabolismo
6.
Proc Natl Acad Sci U S A ; 117(17): 9594-9603, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32277035

RESUMO

Seasonal changes in the environment lead to depression-like behaviors in humans and animals. The underlying mechanisms, however, are unknown. We observed decreased sociability and increased anxiety-like behavior in medaka fish exposed to winter-like conditions. Whole brain metabolomic analysis revealed seasonal changes in 68 metabolites, including neurotransmitters and antioxidants associated with depression. Transcriptome analysis identified 3,306 differentially expressed transcripts, including inflammatory markers, melanopsins, and circadian clock genes. Further analyses revealed seasonal changes in multiple signaling pathways implicated in depression, including the nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway. A broad-spectrum chemical screen revealed that celastrol (a traditional Chinese medicine) uniquely reversed winter behavior. NRF2 is a celastrol target expressed in the habenula (HB), known to play a critical role in the pathophysiology of depression. Another NRF2 chemical activator phenocopied these effects, and an NRF2 mutant showed decreased sociability. Our study provides important insights into winter depression and offers potential therapeutic targets involving NRF2.


Assuntos
Comportamento Animal/fisiologia , Depressão/metabolismo , Regulação da Expressão Gênica/fisiologia , Fator 2 Relacionado a NF-E2/metabolismo , Oryzias/fisiologia , Estações do Ano , Animais , Dimetil Sulfóxido/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Genoma , Mutação , Fator 2 Relacionado a NF-E2/genética
7.
Mol Cell Biochem ; 468(1-2): 129-142, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32185674

RESUMO

Fibrosis process in the liver is a clinical condition established in response to chronic lesions and may be reversible in many situations. In this process, hepatic stellate cells (HSCs) activate and produce extracellular matrix compounds. During fibrosis, the lipid metabolism is also altered and contributes to the transdifferentiation of the HSCs. Thus, controlling lipid metabolism in HSCs is suggested as a method to control or reverse the fibrotic condition. In the search for therapies that modulate lipid metabolism and treat liver diseases, silymarin has been identified as a relevant natural compound to treat liver pathologies. The present study aimed to evaluate the cellular and molecular effects of silymarin in the transdifferentiation process of HSCs (LX-2) from activated phenotype to a more quiesced-like cells , also focusing on understanding the modulatory effects of silymarin on lipid metabolism of HSCs. In our analyses, 100 µM of silymarin reduced the synthesis of actin filaments in activated cells, the synthesis of the protein level of α-SMA, and other pro-fibrotic factors such as CTGF and PFGF. The concentration of 150 µM silymarin did not reverse the activation aspects of LX-2 cells. However, both evaluated concentrations of the natural compound protected the cells from the negative effects of dimethyl sulfoxide (DMSO). Furthermore, we evaluated lipid-related molecules correlated to the transdifferentiation process of LX-2, and 100 µM of silymarin demonstrated to control molecules associated with lipid metabolism such as FASN, MLYCD, ACSL4, CPTs, among others. In contrast, cellular incubation with 150 µM of silymarin increased the synthesis of long-chain fatty acids and triglycerides, regarding the higher presence of DMSO (v/v) in the solvent. In conclusion, silymarin acts as a hepatoprotective agent and modulates the pro-fibrogenic stimuli of LX-2 cells, whose effects depend on stress levels in the cellular environment.


Assuntos
Transdiferenciação Celular/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Cirrose Hepática/metabolismo , Substâncias Protetoras/farmacologia , Silimarina/farmacologia , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Actinas/genética , Actinas/metabolismo , Linhagem Celular , Cromatografia Gasosa , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Dimetil Sulfóxido/toxicidade , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Células Estreladas do Fígado/enzimologia , Células Estreladas do Fígado/metabolismo , Humanos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/genética , Espectrometria de Massas , Triglicerídeos/metabolismo
8.
Toxicol Lett ; 321: 131-137, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31877331

RESUMO

Prior exposures to chemicals/agents may alter epigenome in such a way that subsequent exposure to the same or different xenobiotic would produce different responses. Understanding the mechanism for this "priming" effect is of clinical significance in avoiding adverse drug-drug interactions. Here we reported a dramatic priming effect of dimethyl sulfoxide (DMSO) on pregnane X receptor (PXR)-mediated gene regulations and analyzed the underpinning epigenetic mechanism. We showed that DMSO (1.25-2.5 %) pretreatment has a profound effect in enhancing the expression of PXR target genes. This priming effect persisted up to 48 h. Mechanistically, DMSO pretreatment reduced H4K12 acetylation and therefore enhanced the subsequent rifampicin stimulated histone H4R3 methylation on the regulatory region of PXR target gene CYP3A4. We showed that protein arginine methyltransferase 1 (PRMT1), which methylates H4R3, was important for priming by DMSO. Inhibition of methyltransferase by the pharmacological inhibitor adenosine dialehyde (AdoX), or RNAi knockdown of PRMT1, abolished the DMSO priming effects. On the other hand, Trichostation A (TSA) pretreatment, which increases histone acetylation and therefore suppresses H4R3 methylation, also abolished the DMSO priming effects. Based on the above observation, we proposed a model of sequential order of histone methylation and acetylation on the transcription "relay".


Assuntos
Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Dimetil Sulfóxido/toxicidade , Epigênese Genética/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Histonas/metabolismo , Receptor de Pregnano X/agonistas , Acetilação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Células Hep G2 , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Metilação , Receptor de Pregnano X/genética , Receptor de Pregnano X/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Tempo
9.
Andrologia ; 52(1): e13474, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31710394

RESUMO

Ubiquitin conjugating enzyme (E2) is crucial for mediating N-terminal ubiquitination. Recent study reports that UBE2W is involved in male infertility. However, the correlation between UBE2W expression and hypospermatogenesis is unclear. The present study is to explore the biological role of UBE2W and its association with hypospermatogenesis. Results showed that the sexpression levels of UBE2W in mouse testes were gradually elevated from 2 to 10 weeks, while were significantly deceased in the testes with hypospermatogenesis. When UBE2W expression was successfully down-regulated in spermatogenic cells, the rate of apoptosis was significantly increased and the P53/Bcl-2/caspase 6/caspase 9 signal pathways were activated. Thus, these data indicate that UBE2W down-regulation promotes cell apoptosis and correlates with hypospermatogenesis, which may be helpful for the diagnosis of male infertility.


Assuntos
Azoospermia/patologia , Espermatogênese/fisiologia , Testículo/patologia , Enzimas de Conjugação de Ubiquitina/metabolismo , Animais , Apoptose , Azoospermia/induzido quimicamente , Azoospermia/fisiopatologia , Bussulfano/toxicidade , Linhagem Celular , Dimetil Sulfóxido/toxicidade , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Masculino , Camundongos , RNA Interferente Pequeno/metabolismo , Espermatócitos , Espermatogônias , Enzimas de Conjugação de Ubiquitina/genética
10.
J Vis Exp ; (151)2019 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-31589204

RESUMO

Cytotoxicity is a critical parameter that needs to be quantified when studying drugs that may have therapeutic benefits. Because of this, many drug screening assays utilize cytotoxicity as one of the critical characteristics to be profiled for individual compounds. Cells in culture are a useful model to assess cytotoxicity before proceeding to follow up on promising lead compounds in more costly and labor-intensive animal models. We describe a strategy to identify compounds that affect cell growth in a tdTomato expressing human neural stem cells (NSC) line. The strategy uses two complementary assays to assess cell number. One assay works via the reduction of 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to formazan as a proxy for cell number and the other directly counts the tdTomato expressing NSCs. The two assays can be performed simultaneously in a single experiment and are not labor intensive, rapid, and inexpensive. The strategy described in this demonstration tested 57 compounds in an exploratory primary screen for toxicity in a 96-well plate format. Three of the hits were characterized further in a six-point dose response using the same assay set-up as the primary screen. In addition to providing excellent corroboration for toxicity, comparison of results from the two assays may be effective in identifying compounds affecting other aspects of cell growth.


Assuntos
Técnicas de Cultura de Células/métodos , Meios de Cultura/química , Animais , Contagem de Células , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dimetil Sulfóxido/toxicidade , Humanos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos
11.
Ecotoxicology ; 28(9): 1136-1141, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31559559

RESUMO

Toxicity testing of hydrophobic compounds with low aqueous solubility remains challenging. Dimethyl sulfoxide (DMSO) is widely used as a co-solvent for toxicity testing of hydrophobic chemicals, but it may modulate chemical toxicity patterns. In this study, we critically evaluated the suitability of DMSO as a co-solvent for toxicity testing of hydrophobic organic compounds in aqueous solutions. As the toxicity measure, we used growth inhibition of a natural bacterial community, and the test toxicants included phenol, BTEX (benzene, toluene, ethylbenzene and xylene) and transformation products of polycyclic aromatic hydrocarbons (PAHs). We found that dose-response curves for phenol were unaffected by DMSO concentrations up to 10% (v/v) and that DMSO (5% v/v) did not affect the degree of bacterial growth inhibition for any of the other test compounds in short-term experiments (3.5 h). By contrast, marked co-solvent effects of DMSO were observed in the long-term assay (25 and 27 h). We therefore conclude that DMSO has excellent co-solvent properties for short-term (≤3.5 h) toxicity testing of sparingly water-soluble compounds and its application provides a simple, inexpensive approach for screening of various environmentally relevant hydrophobic chemicals. Importantly, the use of DMSO allows for generation of full dose-responses that may otherwise not be attained.


Assuntos
Bactérias/efeitos dos fármacos , Dimetil Sulfóxido/toxicidade , Poluição por Petróleo/efeitos adversos , Poluentes do Solo/toxicidade , Solventes/toxicidade , Microbiota/efeitos dos fármacos , Microbiologia do Solo , Testes de Toxicidade
12.
Sci Total Environ ; 683: 193-201, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31129327

RESUMO

DMSO is a very common solvent for hydrophobic chemicals that may pose a threat to aquatic organisms. Ectoine (ECT) is a protective amino acid produced by various strains of halophilic bacteria with high potential to alleviate detrimental effects induced by environmental stressors. This amino acid is used in many cosmetics and pharmaceuticals may enter aquatic ecosystems interacting with ions and macromolecules. Little is known on the effects of DMSO and its interaction with ECT on behavioral, physiological and biochemical endpoints of aquatic invertebrates. Therefore, the purpose of the present study was to determine protective effects of DMSO alone and in the combination with ECT on hopping frequency, swimming speed, heart rate, thoracic limb activity, catalase activity and NOx level in an animal model, Daphnia magna subjected to 0.1% and 1% DMSO alone and during combinatorial exposure to ECT (0-25 mg/L) and DMSO for 24 h and 48 h. The results showed that swimming speed, heart rate and thoracic limb activity were inhibited by both 0.1% and 1% DMSO alone however alleviating effects were observed in the combination DMSO + ECT. Thoracic limb activity was higher in the animals exposed to both solutions of DMSO alone, however the parameter was more stimulated at DMSO + ECT. The results suggest that DMSO alone may alter Daphnia behavior and physiological parameters, therefore use of the control group of non-treated animals with DMSO alone would be recommended to avoid data misinterpretation.


Assuntos
Diamino Aminoácidos/farmacologia , Daphnia/efeitos dos fármacos , Dimetil Sulfóxido/toxicidade , Substâncias Protetoras/farmacologia , Poluentes Químicos da Água/toxicidade , Animais , Proteínas de Artrópodes/metabolismo , Catalase/metabolismo , Daphnia/enzimologia , Daphnia/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Movimento/efeitos dos fármacos , Óxido Nítrico/metabolismo , Natação
13.
Poult Sci ; 98(10): 4972-4981, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31111938

RESUMO

An experiment was conducted to investigate the toxicity and tissue distribution of methylsulfonylmethane (MSM) following oral gavage in broilers. A total of four hundred and thirty-two 15-day-old Ross 308 male broilers were allotted to 6 treatments with 6 replicates of 12 birds per replicate and administered a single oral dose of MSM at 0, 50, 100, 300, 1,000, or 2,000 mg/kg BW (Study 1). Another one hundred and sixty-eight 3-day-old chicks were allotted to either control or test group (Study 2) and administered a daily oral gavage of either 0 or 1, 500 mg/kg BW of MSM for 21 D consecutively. Blood and tissue samples were collected over a 48 h (Study 1) or 21 D (Study 2) period and analyzed for MSM concentrations. Toxicity was assessed through changes in hematology and clinical blood chemistry. In Study 1, plasma MSM concentrations were below 167 µg/mL at all time-points in birds receiving up to 300 mg/kg BW, and were significantly higher (P < 0.05) in birds receiving 1,000 or 2,000 mg/kg BW. Similarly, only the highest 2 MSM dosages elicited increased lymphocyte and decreased heterophil counts at 8 h (P < 0.003) and decreased hematocrit at 48 h (P = 0.015). Growth performance variables were unaffected by MSM in Study 2, and plasma and tissue MSM concentrations were highest on study day 21, with MSM-dosed birds always exhibiting higher (P < 0.03) concentrations compared with the control. Birds in Study 2 that were dosed with MSM had decreased liver enzyme concentrations at day 7 and 21 and decreased glucose and phosphorus at day 7. Importantly, MSM was detected in plasma and all tissues of control groups, confirming that MSM is synthesized de novo in chickens. In conclusion, oral MSM at either acute (single dose at 1,000 to 2,000 mg/kg BW) or sub-chronic (1,500 mg/kg BW daily for 21 D) concentrations did not cause any adverse effects on growth or clinical outcomes and appeared to be absorbed and distributed throughout the body.


Assuntos
Ração Animal/toxicidade , Galinhas/metabolismo , Suplementos Nutricionais/toxicidade , Dimetil Sulfóxido/toxicidade , Sulfonas/toxicidade , Administração Oral , Animais , Dieta/veterinária , Relação Dose-Resposta a Droga , Masculino , Distribuição Tecidual
14.
J Hazard Mater ; 369: 763-769, 2019 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-30851516

RESUMO

This study was aimed to develop an objective way of quantifying the reproductive status of the green macroalga, Ulva pertusa using a vital stain and programmed automated analysis (by Image J program). The EC50 values (with 95% CI), the concentrations of toxicants inducing a reduction of 50% in sporulation after 96 h exposure, from the newly developed method were similar to those obtained by the conventional method: 0.651 (0.598-0.705) mg l-1 for Cd, 0.144 (0.110-0.162) mg l-1 for Cu, 0.180 (0.165-0.195) mg l-1 for atrazine, 0.076 (0.049-0.094) mg l-1 for diuron and 30.6 (26.5-34.4) ml l-1 for DMSO, respectively. When the EC50 values from this study were compared to that those from literatures, the sensitivity for some toxicants was similar or higher than that of U. fasciata (1.930 mg l-1 for germination for Cd), U. armoricana (0.250 mg l-1 for Fv/Fm for Cu), U. reticulata (0.126-1.585 mg l-1 for growth for Cu), and U. intestinalis (0.650 mg l-1 for Fv/Fm for atrazine). The subjective views of the experimental performers can be eliminated using the newly developed method. The Ulva method gave consistent responses to Cu and Cd of internationally allowable ranges for effluents, implying that the method is a useful tool for monitoring industrial wastewaters containing these metals.


Assuntos
Clorófitas/química , Ecotoxicologia/métodos , Testes de Toxicidade/métodos , Ulva/química , Atrazina/toxicidade , Cádmio/química , Cádmio/toxicidade , Cobre/química , Cobre/toxicidade , Dimetil Sulfóxido/toxicidade , Diurona/toxicidade , Esporos , Poluentes Químicos da Água/toxicidade
15.
Fish Shellfish Immunol ; 88: 17-27, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30831244

RESUMO

Pharmaceuticals and household chemicals are important components of municipal sewage. Many of them are biologically active, disrupting not only hormonal regulation of aquatic animals but also, indirectly, disturbing their immunological protection. In the environment, chemicals rarely act as individual substances, but as elements of mixtures. Therefore, the aim of this study was to check whether the acute laboratory exposure of common carp juveniles to a mixture of ibuprofen, sodium dodecyl sulphate (SDS), dimethyl sulfoxide (DMSO) and 17 α-ethynylestradiol in increasing concentrations, modifies the levels of innate immunity (lysozyme, C-reactive protein) as well as general stress (metallothioneins, heat shock proteins HSP70) markers in brain, liver, gills, spleen and mucus. The levels of the markers were measured by an immunodetection technique. Not only do the pharmaceuticals and household chemicals impair immunological reactions of young carp in various tissues but also do that in a concentration-dependent manner in the liver, gills, spleen and mucus. This has a very important implication, since it may result in higher sensitivity of young fish to pathogens due to energy allocation to defence processes. The comparisons of the pattern of stress reactions in the studied organ samples indicated that mucus appeared to be a good, non-invasive material for monitoring of environmental state and fish conditions.


Assuntos
Carpas/imunologia , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores , Proteína C-Reativa/análise , Dimetil Sulfóxido/toxicidade , Etinilestradiol/toxicidade , Proteínas de Choque Térmico HSP70/análise , Ibuprofeno/toxicidade , Imunidade Inata , Metalotioneína/análise , Muco/química , Muramidase/análise , Esgotos/química , Dodecilsulfato de Sódio/toxicidade , Estresse Fisiológico , Poluentes Químicos da Água/imunologia
16.
Sci Rep ; 9(1): 4641, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30874586

RESUMO

Though clinical trials for medical applications of dimethyl sulfoxide (DMSO) reported toxicity in the 1960s, later, the FDA classified DMSO in the safest solvent category. DMSO became widely used in many biomedical fields and biological effects were overlooked. Meanwhile, biomedical science has evolved towards sensitive high-throughput techniques and new research areas, including epigenomics and microRNAs. Considering its wide use, especially for cryopreservation and in vitro assays, we evaluated biological effect of DMSO using these technological innovations. We exposed 3D cardiac and hepatic microtissues to medium with or without 0.1% DMSO and analyzed the transcriptome, proteome and DNA methylation profiles. In both tissue types, transcriptome analysis detected >2000 differentially expressed genes affecting similar biological processes, thereby indicating consistent cross-organ actions of DMSO. Furthermore, microRNA analysis revealed large-scale deregulations of cardiac microRNAs and smaller, though still massive, effects in hepatic microtissues. Genome-wide methylation patterns also revealed tissue-specificity. While hepatic microtissues demonstrated non-significant changes, findings from cardiac microtissues suggested disruption of DNA methylation mechanisms leading to genome-wide changes. The extreme changes in microRNAs and alterations in the epigenetic landscape indicate that DMSO is not inert. Its use should be reconsidered, especially for cryopreservation of embryos and oocytes, since it may impact embryonic development.


Assuntos
Dimetil Sulfóxido/metabolismo , Dimetil Sulfóxido/toxicidade , Fenômenos Biológicos , Criopreservação/métodos , Crioprotetores/farmacologia , Metilação de DNA/efeitos dos fármacos , Dimetil Sulfóxido/farmacologia , Desenvolvimento Embrionário/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica , Hepatócitos/efeitos dos fármacos , Humanos , Masculino , MicroRNAs/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Cultura Primária de Células , Solventes/farmacologia , Transcriptoma/efeitos dos fármacos
17.
Neurotox Res ; 35(1): 173-182, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30141144

RESUMO

The developing brain is uniquely susceptible to drug-induced increases in programmed cell death or apoptosis. Many compounds, including anticonvulsant drugs, anesthetic agents, and ethanol, when administered in a narrow postnatal window in rodents, result in increased pruning of neurons. Here, we report that dimethyl sulfoxide (DMSO) triggers widespread neurodegeneration in the immature (postnatal day, P7) rat brain, an effect consistent with a prior report in neonatal mice. We found that the synthetic cannabinoid receptor agonist WIN 55,212-2 (WIN) exerts a neuroprotective effect against DMSO-induced cell death. We extended these findings to determine if WIN is neuroprotective against another drug class known to increase developmental cell death, namely antiseizure drugs. The antiseizure drug phenobarbital (PB) remains the primary treatment for neonatal seizures, despite significantly increasing cell death in the developing rodent brain. WIN exerts antiseizure effects in immature rodent seizure models, but increases the toxicity associated with neonatal ethanol exposure. We thus sought to determine if WIN would protect against or exacerbate PB-induced cell death. Unlike either the prior report with ethanol or our present findings with DMSO, WIN was largely without effect on PB-induced cell death. WIN alone did not increase cell death over levels observed in vehicle-treated rats. These data suggest that WIN has a favorable safety profile in the developing brain and could potentially serve as an adjunct therapy with phenobarbital (albeit one that does not attenuate PB-induced toxicity).


Assuntos
Anticonvulsivantes/farmacologia , Anticonvulsivantes/toxicidade , Benzoxazinas/farmacologia , Dimetil Sulfóxido/toxicidade , Morfolinas/farmacologia , Naftalenos/farmacologia , Fármacos Neuroprotetores/farmacologia , Fenobarbital/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Agonistas de Receptores de Canabinoides/farmacologia , Morte Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/patologia , Distribuição Aleatória , Ratos Sprague-Dawley
18.
Cryobiology ; 86: 95-102, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30458175

RESUMO

We report here a new, unbiased forward genetic method that uses transposon-mediated mutagenesis to enable the identification of mutations that confer cryoprotectant toxicity resistance (CTR). Our method is to select for resistance to the toxic effects of M22, a much-studied whole-organ vitrification solution. We report finding and characterizing six mutants that are resistant to M22. These mutants fall into six independent biochemical pathways not previously linked to cryoprotectant toxicity (CT). The genes associated with the mutations were Gm14005, Myh9, Nrg2, Pura, Fgd2, Pim1, Opa1, Hes1, Hsbp1, and Ywhag. The mechanisms of action of the mutations remain unknown, but two of the mutants involve MYC signaling, which was previously implicated in CT. Several of the mutants may up-regulate cellular stress defense pathways. Several of the M22-resistant mutants were also resistant to dimethyl sulfoxide (Me2SO), and many of the mutants showed significantly improved survival after freezing and thawing in 10% (v/v) Me2SO. This new approach to overcoming CT has many advantages over alternative methods such as transcriptomic profiling. Our method directly identifies specific genetic loci that unequivocally affect CT. More generally, our results provide the first direct evidence that CT can be reduced in mammalian cells by specific molecular interventions. Thus, this approach introduces remarkable new opportunities for pharmacological blockade of CT.


Assuntos
Criopreservação/métodos , Crioprotetores/farmacologia , Crioprotetores/toxicidade , Células-Tronco Embrionárias/citologia , Estresse Fisiológico/genética , Supressão Genética/genética , Animais , Linhagem Celular , Elementos de DNA Transponíveis/genética , Dimetil Sulfóxido/farmacologia , Dimetil Sulfóxido/toxicidade , Etilenoglicol/farmacologia , Etilenoglicol/toxicidade , Formamidas/farmacologia , Formamidas/toxicidade , Congelamento , Camundongos , Camundongos Endogâmicos C57BL , Mutagênese/genética , Estresse Fisiológico/efeitos dos fármacos , Vitrificação/efeitos dos fármacos
19.
J Bioenerg Biomembr ; 50(4): 297-305, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29770896

RESUMO

In this work, the effects of two non-ionic, non-hydroxyl organic solvents, dimethyl sulfoxide (DMSO) and dimethyl formamide (DMF) on the morphology and function of isolated rat hepatic mitochondria were investigated and compared. Mitochondrial ultrastructures impaired by DMSO and DMF were clearly observed by transmission electron microscopy. Spectroscopic and polarographic results demonstrated that organic solvents induced mitochondrial swelling, enhanced the permeation to H+/K+, collapsed the potential inner mitochondrial membrane (IMM), and increased the IMM fluidity. Moreover, with organic solvents addition, the outer mitochondrial membrane (OMM) was broken, accompanied with the release of Cytochrome c, which could activate cell apoptosis signaling pathway. The role of DMSO and DMF in enhancing permeation or transient water pore formation in the mitochondrial phospholipid bilayer might be the main reason for the mitochondrial morphology and function impaired. Mitochondrial dysfunctions induced by the two organic solvents were dose-dependent, but the extents varied. Ethanol (EtOH) showed the highest potential damage on the mitochondrial morphology and functions, followed by DMF and DMSO.


Assuntos
Dimetil Sulfóxido/toxicidade , Dimetilformamida/toxicidade , Mitocôndrias/ultraestrutura , Animais , Citocromos c/metabolismo , Relação Dose-Resposta a Droga , Etanol/toxicidade , Membranas Intracelulares/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , Dilatação Mitocondrial/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Ratos
20.
Sci Rep ; 8(1): 4279, 2018 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-29523856

RESUMO

Diatoms constitute the most diverse group of microalgae and have long been recognised for their large biotechnological potential. In the wake of growing research interest in new model species and development of commercial applications, there is a pressing need for long-term preservation of diatom strains. While cryopreservation using dimethylsulfoxide (DMSO) as a cryoprotective agent is the preferred method for long-term strain preservation, many diatom species cannot be successfully cryopreserved using DMSO. Therefore, in this study, we studied cryopreservation success in six different diatom species, representing the major morphological and ecological diatom groups, using a range of DMSO concentrations and Plant Vitrification Solution 2 (PVS2) as an alternative cryoprotectant to DMSO. In addition, we tested whether suppressing bacterial growth by antibiotics accelerates the post-thaw recovery process. Our results show that the effects of cryoprotectant choice, its concentration and the addition of antibiotics are highly species specific. In addition, we showed that PVS2 and antibiotics are useful agents to optimize cryopreservation of algae that cannot survive the traditional cryopreservation protocol using DMSO. We conclude that a species-specific approach will remain necessary to develop protocols for diatom cryopreservation and to increase their representation in public culture collections.


Assuntos
Criopreservação/métodos , Diatomáceas/efeitos dos fármacos , Crioprotetores/toxicidade , Dimetil Sulfóxido/toxicidade
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