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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
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
10.
Sci Total Environ ; 615: 107-114, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28963892

RESUMO

Dimethyl sulfoxide (DMSO) is a universally used aprotic solvent with the ability to permeate biological membranes and thus is commonly used to achieve appropriate biological availability of hydrophobic toxicants. While DMSO as a carrier medium has a reportedly low toxicity and is routinely employed in ecotoxicology, very little is known about its effect on dynamic behavioral parameters. This study presents a comparative analysis of the lethal and behavioral effects of exposures to DMSO concentrations of 0.1-10% on several test species such as: neonates of the freshwater crustacean Daphnia magna, nauplii of the marine crustacean Artemia franciscana, the marine crustacean Allorchestes compressa, embryos and larvae of the freshwater fish Danio rerio. The results demonstrated that DMSO did not cause statistically significant mortality even at concentrations close to 1% but induced clear and significant behavioral abnormalities in response to sublethal concentrations on all test species. These included hypoactivity syndrome in A. franciscana, A. compressa, D. magna and zebrafish larvae while a slight time-dependent hyperactivity response was observed in zebrafish embryos. For the majority of test species, behavioral changes such as moving distance, acceleration and burst movement were often observed during the first hours of exposure. These results indicate that caution should be exercised when using DMSO as a carrier solvent in experiments assessing behavioral endpoints.


Assuntos
Daphnia/efeitos dos fármacos , Dimetil Sulfóxido/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Animais , Artemia/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Ecotoxicologia , Larva/efeitos dos fármacos , Solventes/toxicidade , Testes de Toxicidade
11.
Theranostics ; 7(19): 4735-4752, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29187900

RESUMO

Rationale: Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water-insoluble substances, a vehicle for drug therapy, and a cryoprotectant for cultured cells. DMSO induced embryonic defects and its mechanism of action remains unclear. The rationale is based on the assumption that DMSO supplementation should induce long-term negative effects on both pre- and post-implantation embryo development. Methods: DMSO induced oxidative stress, ER stress, autophagy, mitophagy, signaling responsible genes and proteins were determined by RT-qPCR, Western blotting, immunofluorescence, and confocal microscopy. DMSO induced mitochondrial dysfunction was measured by transmission electron microcopy and JC-1 assay. Apoptosis was estimated using TUNEL and comet assay. Post-implantation embryo developmental capability was estimated by implantation site and fetus numbers. Results: Exposure to DMSO induced an early oxidative stress response within 0.5 to 2 h in 1-cell zygotes by disrupting the balance of pro- and anti-oxidants. Notably, DMSO-treated 2-cell embryos showed increased expression of unfolded protein response genes such as Hspa5, Hsp90b1, Ddit3, Atf4, and Xbp1. As a result, the development of many embryos is arrested at the 2-cell, 4-cell, or morula stages in a dose-dependent manner. Further, DMSO-induced endoplasmic reticulum stress increased mitochondrial Ca2+ levels, induced mitochondrial depolarization/dysfunction, and induced apoptotic cell death via the JNK/ATF2-dependent pathway. Consequently, treatment with DMSO increased the expression of autophagy initiation-, phagophore elongation-, and autophagosome formation-related genes, as well as localization of PINK1/Parkin, which are the main mediators of mitophagy, in mitochondria. Interestingly, DMSO causes cytotoxic effects in preimplantation embryos by inducing extensive mitophagy and autophagy. Especially, DMSO treatment decreased the inner cell mass and trophectoderm cell numbers as well as mRNA expression of B3gnt5 and Wnt3a in developed blastocysts, which decreased the implantation and developmental rates of full-term offspring after being transferred into pseudopregnant mice. Conclusion: These results provide a significant contribution to finding effective protective agents to combat DMSO mediated reproductive toxicity for application in human embryos in the near future.


Assuntos
Blastocisto/efeitos dos fármacos , Crioprotetores/toxicidade , Dimetil Sulfóxido/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Animais , Apoptose , Autofagia , Blastocisto/metabolismo , Cálcio/metabolismo , Células Cultivadas , Feminino , Camundongos , Dinâmica Mitocondrial , Estresse Oxidativo , Resposta a Proteínas não Dobradas
12.
Cryobiology ; 78: 1-7, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28803845

RESUMO

Low survival of cryopreserved sperm impedes the application of cryopreservation technique in spermcasting oyster species. This study developed a simple method of liquid nitrogen vapor freezing to improve post-thaw sperm survival in the spermcasting oyster Ostrea angasi. The results indicate that the permeable cryoprotectants, dimethyl sulfoxide (DMSO), ethylene glycol (EG) and propylene glycol (PG) were non-toxic to sperm up to 20% concentration and 90 min exposure whereas methanol at 10% or higher was toxic to sperm for any exposure over 30 min. Among the treatments with permeable cryoprotectants, 15% EG produced the highest post-thaw sperm motility. Sperm motility was further improved by the addition of non-permeable cryoprotectants (trehalose and glucose), with 15% EG + 0.2 M trehalose resulting in the highest post-thaw sperm motility among all the combinations evaluated. The durations of 20, 30 and 60 min equilibrations produced a higher post-thaw sperm motility and plasma membrane integrity (PMI) than 10 min. Higher post-thaw motility and PMI were achieved by freezing sperm at the 8 cm height from the liquid nitrogen surface than at the 2, 4, 6, 10 or 12 cm height. Holding sperm for 10 min in liquid nitrogen vapor produced higher post-thaw motility and PMI than for 2, 5 or 20 min. The cryopreservation protocol developed in this study improved both post-thaw motility and PMI of O. angasi sperm at least 15% higher than those cryopreserved using programmable freezing method. Liquid nitrogen vapor freezing might have greater applicability in improving post-thaw sperm quality of spermcasting oyster species.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Criopreservação/métodos , Crioprotetores/toxicidade , Preservação do Sêmen/métodos , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Membrana Celular/efeitos dos fármacos , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologia , Dimetil Sulfóxido/toxicidade , Etilenoglicol/farmacologia , Etilenoglicol/toxicidade , Glucose/farmacologia , Glucose/toxicidade , Masculino , Metanol/farmacologia , Metanol/toxicidade , Ostrea , Propilenoglicol/farmacologia , Propilenoglicol/toxicidade , Trealose/farmacologia , Trealose/toxicidade
13.
Reprod Biomed Online ; 35(3): 311-313, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28645837

RESUMO

There have been 60 births after transplantation of cryopreserved ovarian tissue: 58 using the slow freezing method, and two using the vitrification method. DMSO and EG are widely used as cryoprotectants. However DMSO is a known epimutagen, and EG has been reported to be toxic in high concentrations. In this study, we measured residual DMSO and EG in ovarian tissue after vitrification and slow freezing. Cryoprotectants remained at a high concentration in the vitrified/warmed ovarian tissue just before transplantation (DMSO: 9.8 mg/g, EG: 9.8 mg/g). We must consider the impact of the cryoprotectants on the mother and the baby.


Assuntos
Criopreservação , Dimetil Sulfóxido/farmacologia , Resíduos de Drogas/toxicidade , Etilenoglicol/farmacologia , Oócitos/efeitos dos fármacos , Ovário , Células Cultivadas , Criopreservação/métodos , Crioprotetores/farmacologia , Crioprotetores/toxicidade , Dimetil Sulfóxido/toxicidade , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , Etilenoglicol/toxicidade , Feminino , Congelamento , Humanos , Recém-Nascido , Exposição Ocupacional/efeitos adversos , Oócitos/química , Oócitos/citologia , Folículo Ovariano/química , Folículo Ovariano/citologia , Folículo Ovariano/efeitos dos fármacos , Ovário/química , Ovário/efeitos dos fármacos , Gravidez , Vitrificação
14.
Environ Toxicol Chem ; 36(10): 2631-2639, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28337778

RESUMO

Carrier solvents are often used in aquatic toxicity testing for test chemicals with hydrophobic properties. However, the knowledge of solvent effects on test organisms remains limited. The present study aimed to determine the biochemical effects of the 4 common solvents methanol, ethanol, acetone, and dimethyl sulfoxide (DMSO) on 2 test species, Lemna minor and Raphidocelis subcapitata, by applying Fourier transform infrared spectroscopy (FTIR) coupled with multivariate analysis to select appropriate solvents for toxicity testing. The results showed biochemical variations associated with solvent treatments at different doses on test species. From the infrared spectra obtained, the structures of lipid membrane and protein phosphorylation in the test species were found to be sensitive to the solvents. Methanol and ethanol mainly affected the protein secondary structure, whereas acetone and DMSO primarily induced alterations in carbohydrates and proteins in the test species. The FTIR results demonstrated that methanol and ethanol showed higher biochemical alterations in the test species than acetone and DMSO, especially at the high doses (0.1 and 1% v/v). Based on the growth inhibition displayed and FTIR spectroscopy, acetone, and DMSO can be used as carrier solvents in toxicity testing when their doses are lower than 0.1% v/v. Environ Toxicol Chem 2017;36:2631-2639. © 2017 SETAC.


Assuntos
Araceae/efeitos dos fármacos , Clorófitas/efeitos dos fármacos , Solventes/toxicidade , Acetona/toxicidade , Araceae/crescimento & desenvolvimento , Clorófitas/crescimento & desenvolvimento , Dimetil Sulfóxido/toxicidade , Análise Discriminante , Etanol/toxicidade , Metanol/toxicidade , Análise Multivariada , Análise de Componente Principal , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Testes de Toxicidade
15.
J Pediatr Hematol Oncol ; 39(5): e297-e299, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28121745

RESUMO

Dimethyl sulfoxide (DMSO) is a cryoprotective agent used in storage of frozen stem cells in stem cell transplantation. Central nervous system side effects of DMSO such as epileptic seizures, stroke, transient global amnesia, and temporary leucoencephalopathy are rarely seen. Here, we report a pediatric patient who developed seizures after DMSO-cryopreserved stem cell infusion and whose magnetic resonance imaging of the brain demonstrated parietal and occipital focal cortical T2-signal intensity increase. DMSO toxicity should be kept in mind in patients who received cryopreserved stem cell infusion and magnetic resonance imaging may be helpful in differential diagnosis of central nervous system involvement.


Assuntos
Crioprotetores/toxicidade , Dimetil Sulfóxido/toxicidade , Síndromes Neurotóxicas/etiologia , Transplante de Células-Tronco/efeitos adversos , Adolescente , Aloenxertos , Criopreservação/métodos , Diagnóstico Diferencial , Dimetil Sulfóxido/uso terapêutico , Feminino , Humanos , Síndromes Neurotóxicas/diagnóstico por imagem
16.
Brain Res Bull ; 128: 34-39, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27836802

RESUMO

BACKGROUND: Dimethyl sulfoxide (DMSO) is a widely used solvent and vehicle for in vivo and in vitro administration of test compounds. Effects of DMSO independent of the test compound, such as in studies examining morphological plasticity or neurotoxic responses, may lead to spurious results. AIM: To investigate effects of DMSO concentration ([DMSO]) on morphology and survival of primary cultured neurons and astrocytes. METHODS: Primary cultured neurons and astrocytes were treated with 0.25%-10.00% [DMSO] for 12-48h. Viable cell number and morphology were compared to untreated cultures using the CCK-8 assay and phase-contrast microscopy. Expression levels of the neuronal marker NeuN and astrocyte marker glial fibrillary acidic protein (GFAP) were determined by immunofluorescence and western blotting. RESULTS: A [DMSO]≤0.50% had no effect on neuronal number or NeuN expression up to 24h, while ≥1.00% induced a progressive and dramatic loss of both viability and NeuN expression even after 12h. Brief (12h) exposure to ≤1.00% DMSO had no effect on astrocytes survival or GFAP expression, while ≥5.00% significantly reduced both at all exposure durations. In contrast to neurons, exposure to 0.50% and 1.00% DMSO for 24 or 48h enhanced astrocytes proliferation and GFAP expression. Astrocytic processes were maintained at 0.50% and 1.00% DMSO, while neurons exhibited marked neurite retraction at ≥0.50%. CONCLUSION: A [DMSO]≥0.5% markedly disrupts neuronal morphology and reduces viability, even after brief exposure. In astrocytes, 0.50% and 1.00% DMSO appear to induce reactive gliosis. For treatment of neural cells, [DMSO] should be ≤0.25% to obviate spurious vehicle effects.


Assuntos
Astrócitos/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dimetil Sulfóxido/toxicidade , Neurônios/efeitos dos fármacos , Animais , Antígenos Nucleares/metabolismo , Astrócitos/metabolismo , Astrócitos/patologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Relação Dose-Resposta a Droga , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Ratos Sprague-Dawley , Fatores de Tempo
17.
Zebrafish ; 14(1): 60-68, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27509300

RESUMO

Dimethyl sulfoxide (DMSO), a widely used carrier solvent, can be toxic to test organisms and has species-specific sensitivity. In this study, the developmental toxicity and stress protein responses of DMSO to rare minnow (Gobiocypris rarus) and zebrafish (Danio rerio) with two tests were compared in the early life stage. In the first test, fertilized eggs were exposed to 0%, 0.0001%, 0.001%, 0.01%, 0.1%, 1.0%, 1.5%, and 2.0% v/v of DMSO until 3 days post hatching. In the second test, larvae from 0 to 8 d were exposed to 2% DMSO until 4 days. Our results showed that DMSO was toxic to rare minnow and zebrafish on multiple indexes, and the no-observed-effect concentrations of DMSO in both species were 1.0% and 0.001% for developmental toxicity analysis and stress protein analysis, respectively. Furthermore, rare minnow larvae were more sensitive than zebrafish to DMSO for spinal malformation. The sensitive period for induction of spinal malformation by DMSO was 0-7 d after hatch (dah) for rare minnow and 0-4 dah for zebrafish. Together, these results will provide support to the use of DMSO in ecotoxicological studies using rare minnow and will contribute to a better understanding of the toxicity of DMSO.


Assuntos
Cyprinidae/embriologia , Dimetil Sulfóxido/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Depuradores de Radicais Livres/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Peixe-Zebra/embriologia , Anormalidades Induzidas por Medicamentos , Animais , Peso Corporal/efeitos dos fármacos , Cyprinidae/metabolismo , Relação Dose-Resposta a Droga , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/metabolismo , Taxa de Sobrevida , Testes de Toxicidade Aguda , Peixe-Zebra/metabolismo
18.
Toxicol Appl Pharmacol ; 307: 130-137, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27495897

RESUMO

The scarcity of studies on boron containing compounds (BCC) in the medicinal field is gradually being remedied. Efforts have been made to explore the effects of BCCs due to the properties that boron confers to molecules. Research has shown that the safety of some BCCs is similar to that found for boron-free compounds (judging from the acute toxicological evaluation). However, it has been observed that the administration of 3-thienylboronic acid (3TB) induced motor disruption in CD1 mice. In the current contribution we studied in deeper form the disruption of motor performance produced by the intraperitoneal administration of 3TB in mice from two strains (CD1 and C57BL6). Disruption of motor activity was dependent not only on the dose of 3TB administered, but also on the DMSO concentration in the vehicle. The ability of 3TB to enter the Central Nervous System (CNS) was evidenced by Raman spectroscopy as well as morphological effects on the CNS, such as loss of neurons yielding biased injury to the substantia nigra and striatum at doses ≥200mg/kg, and involving granular cell damage at doses of 400mg/kg but less injury in the motor cortex. Our work acquaints about the use of this compound in drug design, but the interesting profile as neurotoxic agent invite us to study it regarding the damage on the motor system.


Assuntos
Ácidos Borônicos/toxicidade , Encéfalo/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Dimetil Sulfóxido/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Testes de Toxicidade Aguda , Tremor/induzido quimicamente
19.
PLoS One ; 11(6): e0158074, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27348312

RESUMO

Meiotic maturation of mammalian oocytes is a precisely orchestrated and complex process. Dimethyl sulfoxide (DMSO), a widely used solvent, drug, and cryoprotectant, is capable of disturbing asymmetric cytokinesis of oocyte meiosis in mice. However, in pigs, DMSO's effect on oocyte meiosis still remains unknown. We aimed to evaluate if DMSO treatment will affect porcine oocyte meiosis and the underlying molecular changes as well. Interestingly, we did not observe the formation of the large first polar body and symmetric division for porcine oocytes treated with DMSO, contrary to findings reported in mice. 3% DMSO treatment could inhibit cumulus expansion, increase nuclear abnormality, disturb spindle organization, decrease reactive oxygen species level, and elevate mitochondrial membrane potential of porcine oocytes. There was no effect on germinal vesicle breakdown rate regardless of DMSO concentration. 3% DMSO treatment did not affect expression of genes involved in spindle organization (Bub1 and Mad2) and apoptosis (NF-κB, Pten, Bcl2, Caspase3 and Caspase9), however, it significantly decreased expression levels of pluripotency genes (Oct4, Sox2 and Lin28) in mature oocytes. Therefore, we demonstrated that disturbed cumulus expansion, chromosome alignment, spindle organization and pluripotency gene expression could be responsible for DMSO-induced porcine oocyte meiotic arrest and the lower capacity of subsequent embryo development. Our results provide new insights on DMSO's effect on porcine oocyte meiosis and raise safety concerns over DMSO's usage on female reproduction in both farm animals and humans.


Assuntos
Ciclo Celular , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologia , Meiose , Oócitos/efeitos dos fármacos , Fuso Acromático/efeitos dos fármacos , Animais , Apoptose , Núcleo Celular/efeitos dos fármacos , Crioprotetores/toxicidade , Dimetil Sulfóxido/toxicidade , Feminino , Mitocôndrias/efeitos dos fármacos , Oócitos/citologia , Suínos
20.
Sci Rep ; 6: 25515, 2016 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-27149165

RESUMO

Nasopharyngeal cancer or nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. The factors that induce nasopharyngeal cancer are still not clear. Additional information about the chemicals or genes related to nasopharyngeal cancer will promote a better understanding of the pathogenesis of this cancer and the factors that induce it. Thus, a computational method NPC-RGCP was proposed in this study to identify the possible relevant chemicals and genes based on the presently known chemicals and genes related to nasopharyngeal cancer. To extensively utilize the functional associations between proteins and chemicals, a heterogeneous network was constructed based on interactions of proteins and chemicals. The NPC-RGCP included two stages: the searching stage and the screening stage. The former stage is for finding new possible genes and chemicals in the heterogeneous network, while the latter stage is for screening and removing false discoveries and selecting the core genes and chemicals. As a result, five putative genes, CXCR3, IRF1, CDK1, GSTP1, and CDH2, and seven putative chemicals, iron, propionic acid, dimethyl sulfoxide, isopropanol, erythrose 4-phosphate, ß-D-Fructose 6-phosphate, and flavin adenine dinucleotide, were identified by NPC-RGCP. Extensive analyses provided confirmation that the putative genes and chemicals have significant associations with nasopharyngeal cancer.


Assuntos
Carcinoma/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Interação Gene-Ambiente , Neoplasias Nasofaríngeas/genética , Nasofaringe/efeitos dos fármacos , 2-Propanol/toxicidade , Antígenos CD/genética , Antígenos CD/metabolismo , Proteína Quinase CDC2/genética , Proteína Quinase CDC2/metabolismo , Caderinas/genética , Caderinas/metabolismo , Carcinoma/induzido quimicamente , Carcinoma/metabolismo , Carcinoma/patologia , Dimetil Sulfóxido/toxicidade , Flavina-Adenina Dinucleotídeo/toxicidade , Frutosefosfatos/toxicidade , Perfilação da Expressão Gênica , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismo , Humanos , Fator Regulador 1 de Interferon/genética , Fator Regulador 1 de Interferon/metabolismo , Ferro/toxicidade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/induzido quimicamente , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Nasofaringe/metabolismo , Nasofaringe/patologia , Propionatos/toxicidade , Receptores CXCR3/genética , Receptores CXCR3/metabolismo , Fosfatos Açúcares/toxicidade
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