Unexpected low‐dose toxicity of the universal solvent DMSO

Galvão, Joana; Davis, Benjamin; Tilley, Mark; Normando, Eduardo; Duchen, Michael R.; Cordeiro, M. Francesca

doi:10.1096/fj.13-235440

Cited by 532 publications

(395 citation statements)

References 77 publications

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“…However, this organic solvent can be cytotoxic by disrupting the cell membranes or inducing apoptosis. 11 The use of pools containing high numbers of peptides can lead to substantial concentration of DMSO in the culture medium, which raises concerns with regard to the detection of intact T-cell responses. Thus, we first analyzed the impact of different DMSO concentrations on CD8 C and CD4 C T-cell proliferation (Fig.…”

Section: Resultsmentioning

confidence: 99%

High-throughput monitoring of human tumor-specific T-cell responses with large peptide pools

et al. 2015

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In immune intervention trials, the comprehensive investigation of immunogenicity or T-cell epitope-mapping is challenging especially when a large set of epitopes needs to be screened and limited sample material is available. To this end, T-cell responses are often monitored using peptide pools. Here, we assessed the magnitude and sensitivity of detection of antigen-specific CD8 C and CD4 C T cells using a single peptide alone or mixed into large pools. Interestingly the magnitude of ex vivo anti-viral and anti-tumor T-cell responses was identical irrespective of the presence and number of irrelevant peptides, in different functional assays with PBMCs from healthy donors and cancer patients. Moreover, the presence of up to 300 irrelevant peptides did not affect the threshold of responsiveness of antigen-specific CD8 C T cells to single cognate peptides. These data demonstrate the relevance of using very large peptide pools for the sensitive and specific immune-monitoring of epitope-specific T cells in natural or immunemodulated context.

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Section: Resultsmentioning

confidence: 99%

High-throughput monitoring of human tumor-specific T-cell responses with large peptide pools

et al. 2015

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“…This characteristic, in addition to its low toxicity, has led to its ubiquitous use and widespread application (35). A great number of toxicological and medical studies are performed with DMSO to determine the safety of this chemical (10,27). Although clinically beneficial in some situations, DMSO can have some adverse side effects.…”

Section: Discussionmentioning

confidence: 99%

“…Since cell based assays should be validated based on cytotoxic effects of solvents used, the current study highlighted safety concerns of using some preferred organic solvents in biological assays. Some researchers recommended that to solubilize compounds, it is better to compute absolute solvent final concentrations and include an untreated control group in addition to solvent vehicle control to check for its toxicity (10). Also, some others emphasize on the need to lower the concentrations of solvents in toxicology tests as far as possible (3, 42).…”

Section: Discussionmentioning

confidence: 99%

“…Several authors have reported interference of frequently used solvents with cellular based assays (8,9). Therefore, the solvent should be selected to optimize the solubility of poor water-soluble compound without adversely affecting the assay conducts, such as cell growth (10). Thus, the cell growth inhibition and cytotoxicity study of organic solvents are very essential and necessary.…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxic Effects of Some Common Organic Solvents on MCF-7, RAW-264.7 and Human Umbilical Vein Endothelial Cells

Jamalzadeh¹,

Ghafoori²,

Sariri³

et al. 2016

Avicenna J Med Biochem

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Background: Organic solvents are widely used in cell biology experiments. Despite increasing the solubility, they have some moderate toxic effects. Therefore, selecting the appropriate solvent along with the use of suitable concentration insures the accuracy and reliability of experimental results. Objectives: The current study aimed to examine the cytotoxic effects of some organic solvents on various cell models including MCF-7, RAW-264.7 and human umbilical vein endothelial cells (HUVEC). Materials and Methods:To evaluate the cytotoxicity effect of common organic solvents on the MCF-7, RAW-264.7 and HUVEC cells, multi-table tournament (MTT) colorimetric assay, the widely used and validated cytotoxicity test was applied. For this purpose, the selected cells were treated with different concentrations (0, 0.1%, 0.5%, 1%, 1.5%, 2%, 3% and 5% v/v) of four most commonly used organic solvents (acetone, ethanol, dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) and then subjected to MTT experiment. Results: According to the obtained results, the cytotoxicity increased significantly with increasing the concentration of all four solvents compared to that of the control group. Studies with MCF-7, RAW-264.7 and HUVEC suggested that acetone, ethanol and DMSO at concentrations of 0.1% and 0.5%, had little or no toxicity, whereas higher concentrations inhibited the growth of all three cells. Compared with other three solvents, DMF displayed rather greater toxicity. Based on the results, proliferation of MCF-7, RAW-264.7 and HUVEC cells were inhibited by all used organic solvents, dose dependently. Conclusions: Thus, the background experimental error can be reduced remarkably by maximal concentration of 0.5% ethanol, acetone and DMSO and 0.1% DMF in the final treatment medium.

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“…Penetrating cryoprotectants, such as glycerol and dimethyl sulfoxide (DMSO), change fluid properties and increase membrane glass‐phase transition temperature, which results in reduced intracellular ice formation (Hubalek, 2003; Fowler and Toner, 2005). Nevertheless, DMSO is not recommended for in vivo administrations as it was found to be toxic to cells at low concentrations of 2–4% (Galvao et al ., 2014), whereas glycerol is a common additive for frozen faecal samples also in stool banks (Aguirre et al ., 2015). The clinical efficacy of cryopreserved faecal slurries for resolving RCDI has been investigated before.…”

Section: Introductionmentioning

confidence: 99%

Cryopreservation of artificial gut microbiota produced with in vitro fermentation technology

Bircher

Schwab

Geirnaert

et al. 2017

Microbial Biotechnology

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SummaryInterest in faecal microbiota transplantation (FMT) has increased as therapy for intestinal diseases, but safety issues limit its widespread use. Intestinal fermentation technology (IFT) can produce controlled, diverse and metabolically active ‘artificial’ colonic microbiota as potential alternative to common FMT. However, suitable processing technology to store this artificial microbiota is lacking. In this study, we evaluated the impact of the two cryoprotectives, glycerol (15% v/v) and inulin (5% w/v) alone and in combination, in preserving short‐chain fatty acid formation and recovery of major butyrate‐producing bacteria in three artificial microbiota during cryopreservation for 3 months at −80°C. After 24 h anaerobic fermentation of the preserved microbiota, butyrate and propionate production were maintained when glycerol was used as cryoprotectant, while acetate and butyrate were formed more rapidly with glycerol in combination with inulin. Glycerol supported cryopreservation of the Roseburia spp./Eubacterium rectale group, while inulin improved the recovery of Faecalibacterium prausnitzii. Eubacterium hallii growth was affected minimally by cryopreservation. Our data indicate that butyrate producers, which are key organisms for gut health, can be well preserved with glycerol and inulin during frozen storage. This is of high importance if artificially produced colonic microbiota is considered for therapeutic purposes.

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Unexpected low‐dose toxicity of the universal solvent DMSO

Cited by 532 publications

References 77 publications

High-throughput monitoring of human tumor-specific T-cell responses with large peptide pools

High-throughput monitoring of human tumor-specific T-cell responses with large peptide pools

Cytotoxic Effects of Some Common Organic Solvents on MCF-7, RAW-264.7 and Human Umbilical Vein Endothelial Cells

Cryopreservation of artificial gut microbiota produced with in vitro fermentation technology

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