Ion transport through dimethyl sulfoxide (DMSO) induced transient water pores in cell membranes

Abstract

It is well known that dimethyl sulphoxide (DMSO) increases membrane permeability, which makes it widely used as a vehicle to facilitate drug delivery across biological membranes. However, the mechanism of how DMSO increases membrane permeability has not been well understood. Recently, molecular dynamics simulations have demonstrated that DMSO can induce water pores in biological membranes, but no direct experimental evidence is so far available to prove the simulation result. Using FluxOR Tl⁺ influx assay and intracellular Ca²⁺ imaging technique, we studied the effect of DMSO on Tl⁺ and Ca²⁺ permeation across cell membranes. Upon application of DMSO on CHO-K1 cell line, Tl⁺ influx was transiently increased in a dose-dependent manner. The increase in Tl⁺ permeability induced by DMSO was not changed in the presence of blockers for K⁺ channel and Na⁺-K⁺ ATPase, suggesting that Tl⁺ permeates through transient water pores induced by DMSO to enter into the cell. In addition, Ca²⁺ permeability was significantly increased upon application of DMSO, indicating that the transient water pores induced by DMSO were non-selective pores. Furthermore, similar results could be obtained from RAW264.7 macrophage cell line. Therefore, this study provided experimental evidence to support the prediction that DMSO can induce transient water pores in cell membranes, which in turn facilitates the transport of active substances across membranes.

The extracellular matrix protein EMILIN1 silences the RAS-ERK pathway via α4β1 integrin and decreases tumor cell growth

“…DMSO can induce transient water pores in cell membranes increasing permeability [29]. Ca 2+ can easily flow through these pores [30, 31].…”

Histological evaluation of the repair process of replanted rat teeth after storage in resveratrol dissolved in dimethyl sulphoxide

“…How the R+DMSO combination is administered may also be questioned, because there was good alveolar preservation in rats with periodontitis after the use of resveratrol diluted in DMSO applied in daily subcutaneous injections over a period of several weeks (ie, systematically) and for a longer period of time. This is another fact that would contradict the good results of this compound recently brought forward by several authors and the good properties of DMSO as a vehicle …”

“…In this study, DMSO was used to increase the solubility and absorption of resveratrol in cells of the periodontal ligament, rather than ethanol. Ethanol acts via the acetylation of resveratrol, which enhances solubility and the capacity to capture cells (50 mg/mL), whereas DMSO as a vehicle creates water pores in the membrane water, something that may have impaired the absorption of resveratrol, which is insoluble in water . In addition, resveratrol is absorbed either by passive diffusion or through the formation of complexes with membrane receptors such as the integrins or fatty acids that make the lipophilic environment propitious for resveratrol, thus making its cellular absorption efficient …”

“…Therefore, other vehicles have been studied, such as resveratrol dissolved in DMSO, considering that the latter is capable of increasing cell permeability and inducing the passage of water through the cell membrane. This can facilitate the transport of active substances through these membranes, also allowing the passage of bigger molecules …”

The localization of primary efferent sympathetic neurons innervating the porcine thymus – a retrograde tracing study

“…The observed discrepancies may be explained by the physicochemical properties of both tracers (Schofield 2008) as well as the properties of the vehicles used. According to the supplier's recommendation, DiI was dissolved in DMSO, which per se increases the cell membranes permeability (He et al 2012) and thus may help the tracer to spread inside the organ. This simply explains why substantially greater total numbers of thymusprojecting neurons were observed after DiI than FB application.…”