Cutaneous and Ocular Toxicology

ISSN: 1556-9527 (Print) 1556-9535 (Online) Journal homepage: http://www.tandfonline.com/loi/icot20

Dimethyl sulfoxide could be a useful probe to evaluate unusual skin angioneurotic reaction and epidermal permeability Shuang Y. Chen, Xue M. Wang, Yan Q. Liu, Yan R. Gao, Xiao P. Liu, Shu Y. Li & Ya Q. Dong To cite this article: Shuang Y. Chen, Xue M. Wang, Yan Q. Liu, Yan R. Gao, Xiao P. Liu, Shu Y. Li & Ya Q. Dong (2014) Dimethyl sulfoxide could be a useful probe to evaluate unusual skin angioneurotic reaction and epidermal permeability, Cutaneous and Ocular Toxicology, 33:1, 63-69, DOI: 10.3109/15569527.2013.821615 To link to this article: http://dx.doi.org/10.3109/15569527.2013.821615

Published online: 05 Aug 2013.

Submit your article to this journal

Article views: 44

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=icot20 Download by: [Texas A & M International University]

Date: 05 November 2015, At: 20:10

http://informahealthcare.com/cot ISSN: 1556-9527 (print), 1556-9535 (electronic) Cutan Ocul Toxicol, 2014; 33(1): 63–69 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/15569527.2013.821615

RESEARCH ARTICLE

Dimethyl sulfoxide could be a useful probe to evaluate unusual skin angioneurotic reaction and epidermal permeability Shuang Y. Chen1,2, Xue M. Wang2, Yan Q. Liu1, Yan R. Gao3, Xiao P. Liu3, Shu Y. Li4, and Ya Q. Dong1 Dermatological Department, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China, 2Skin & Cosmetic Research Department, Shanghai Skin Disease Hospital, Shanghai, China, 3Shanghai Skin Disease Hospital Clinical School of Anhui Medical University, Shanghai, China, and 4 Tongji Hospital of Tongji University, Shanghai, China Abstract

Keywords

Background/objectives: Dimethyl sulfoxide (DMSO) has been suggested as a traditional chemical probe for assessing skin susceptibility and barrier function. The purpose of this study was to determine the role of DMSO test for the evaluation of unusual skin angioneurotic reaction and epidermal permeability. Methods: Thirty healthy volunteers were exposed to 98% DMSO on the flexor forearm skin for three exposure durations (5 min, 10 min and 15 min). Clinical visual score and biological physical parameters were obtained. The volunteers were divided into two groups according to the clinical visual scoring. The skin parameters were subsequently analyzed. Results: There was a significant correlation between clinical visual score and biological physical parameters. The skin color parameters (a*, oxyhemoglobin, erythema and melanin index) and blood flow values were significant between two groups regardless of duration of DMSO exposure, and a significant difference between density values could also be detected if we regrouped the volunteers according to the sting-producing score. Our results also suggested there was no correlation between questionnaire score and clinical visual score or other parameters. Conclusions: Application of 98% DMSO for 10 min combined with a* (at 30 min) and blood flow (at 10 min) values could help us to identify persons with a hyper-angionerotic reaction to chemical stimulus. The penetrative activity of DMSO correlated with the thickness of the individual’s skin.

Angioneurotic reaction, chemical probe, non-invasive methods, permeability

Introduction Dimethyl sulfoxide (DMSO) has been used to diminishing the stratum corneum (SC) barrier function as a classic penetration enhancer. DMSO applied to the skin surface can cause visible non-immunologic contact urticaria or erythema. The magnitude of this skin reaction represents obvious dosedependences and individual differences1,2. The DMSO test, designed by Frosch, is considered a quick and reliable test of skin barrier function to identify persons with an unusual susceptibility to irritants2. Although its mechanisms of action remain unclear3, in vitro and in vivo studies suggested that DMSO-induced skin inflammation is characterized by cellular vacuolization in the epidermis and dermal leukocyte infiltration2,4. For many individuals, the adverse reactions associated with skin contact to house products or cosmetics are not those due to irritation or allergy. An objective and quantitative test to identify persons with an unusual

Address for correspondence: Xue M. Wang, MD, Skin & Cosmetic Research Department, Shanghai Skin Disease Hospital, 1278 Bao De Road, Shanghai 200443, China. E-mail: [email protected]

History Received 28 February 2013 Revised 12 June 2013 Accepted 27 June 2013 Published online 9 August 2013

angioneurotic reaction to external stimulus would be valuable for numerous health enhancing and therapeutic benefits. The study described herein entails a group of human volunteers exposed to a 98% DMSO solution for different exposure duration period to examine their clinical adverse reactions. This study attempts to determine the magnitude of DMSO-inducing responses by clinical evaluation and non-invasive bioengineering methods, and to discover the suitable endpoints to identify persons with an angioneurotic reaction and the epidermal permeability for acute chemical stimulus.

20 14

Downloaded by [Texas A & M International University] at 20:10 05 November 2015

1

Materials and methods Subjects The study consisted of 30 screened healthy Chinese participants without any skin disease at the time of study. The participants were 14 males and 16 females, between the ages of 20- to 45-year-old. The protocol of this test had passed review by the ethical commission of the Shanghai Skin Disease Hospital (2012–09) and all volunteers gave their informed consent before the study.

64

S. Y. Chen et al.

Material and application DMSO (purity499%, Bio Basic Inc, Ontario, Canada) was diluted in water (containing 0.09% NaCl) to obtain a final concentration of 98%2,5. Three squares, with a diameter of 1.5 cm, equally spaced, were marked on the flexor side of forearm skin for topical applications of 30 ml 98% DMSO solution on either the left or the right arm. The three square test areas correspond to the three exposure durations of 15 min, 10 min and 5 min, respectively. For the ease of data recording, these three exposure durations were designated as ‘‘A1’’, ‘‘A2’’ and ‘‘A3’’ separately. After the elapse of exposure duration, the DMSO solution was removed and the test sites were dried with a tissue gently.

Downloaded by [Texas A & M International University] at 20:10 05 November 2015

Sensitive skin questionnaire Each of the participants fills a questionnaire to evaluate selfperceived skin sensitivity (SPSS) prior to the study. The questionnaire contained 29 items and was designed to provide accurate information about individual participant’s sensitive skin status6,7. The participants were categorized as selfperceived-sensitive based on the total score from the questionnaire. Clinical evaluation Clinical visual scoring of the skin response to DMSO was performed at 10 min, 30 min and 60 min after removal of

Cutan Ocul Toxicol, 2014; 33(1): 63–69

DMSO, according to the following criteria (Figure 1)8. The 98% DMSO application on the skin might also induce upset sensation (such as a sting) after 2 to 15 min, hence a stingproducing time scale was designed to measure the DMSOrelated adverse sensation. A ‘‘sting-producing score’’ for each test site was devised and recorded according to the time of sensing stinging after DMSO application: if the stingproducing time 2.5 min, sting-producing score was recorded as 3 points; 5 min was recorded as 2 points; 15 min was recorded as 1 point; no sensation of sting was recorded as 0 point. Non-invasive measurement Biophysical parameters were obtained at the test areas four times during the study, including baseline, 10 min, 30 min and 60 min after removal the test material. The instruments were listed below. The baseline values from unexposed skin were obtained at the start of the study. The whole study was conducted in a strictly controlled condition with a temperature of 20  2 C and a relative humidity of 40–60%. MexameterÕ MX16 (Courage þ Khazaka electronic Gmbh, Cologne, Germany) is a narrow-band reflectance spectrophotometer which is designed to measure the intensity of erythema (erythema index, EI) and melanin pigmentation (melanin index, MI). This reflectance meter measures is based on the optical principle as developed by Diffey9.

Figire 1. The images of the 0–3 scale for visual scoring of Erythemas and Wheals after application.

Downloaded by [Texas A & M International University] at 20:10 05 November 2015

DOI: 10.3109/15569527.2013.821615

It measures absorbed and reflected light at wavelengths for hemoglobin (green and red) and for melanin (red and near-infrared). MI is automatically computed from the intensities of absorbed and reflected light at 660 and 880 nm, respectively; EI is computed from the intensity of the absorbed and the reflected light at, respectively, 568 and 660 nm. ChromameterÕ CR400 (Konica MinoltaÕ , Tokyo, Japan) is probably the most widely used tristimulus instrument which illuminates the skin with a pulsed xenon arc lamp. The light reflected perpendicular to the surface is collected for a tristimulus color analysis at 450, 560 and 600 nm, using the L*a*b* color system, as determined by the CIE10. The L* value from a reading expresses the relative brightness of color (ranging from black to white) and along with the b* value is used to measure pigmentation; the a* value best captures erythema or skin redness. Diffuse Reflectance Spectromater (DRS) (USB 2000þ, Ocean Optics, Dunedin, FL) is a non-invasive technique which uses the diffusion approximation to analyze tissue reflectance spectra11. Through the analysis and conversion, the parameters of oxyhemoglobin (Oxy HbO), deoxyhemoglobin (Deoxy Hb), Melanin and Scattering can be recorded to discribe the skin condition. The Full-field Laser Perfusion Imager (moorFLPI) (Moor Instruments Ltd, Axminster, UK) was used for measuring the cutaneous blood flow (BF)12. The laser can produce a (785  10) nm wavelength of coherent light, which onto the skin can be reflected and scattered by the stationary or moving tissues. The Doppler-shifted light which backscattered from moving blood cells is directly related to the red blood flow, so using the laser scanning the skin can evaluate organization of total microcirculation BF. Ultrascan UC22 (Courage þ Khazaka electronic Gmbh, Cologne, Germany) is a non-invasive scanning device, with a pulse-generator produces short electrical pulses which are transformed piezoelectrically to ultrasound signals by means of a special 22 MHz ultrasound transducer. The ultrasound signals which are transmitted to the skin and produce reflections are digitized, stored by the computer, post processed, and then an ultrasound image is displayed.

DMSO used in skin angioneurotic reaction and permeability

65

Clinical evaluation The subjects were divided into two groups according to the clinical visual scoring. The participants with total score 520 points were categorized as Group 1, and considered as ‘‘non-reactors’’ (n ¼ 15). The rest of subjects with a total score 20 points were categorized as Group 2, and considered as ‘‘reactors’’ (n ¼ 15). After various exposure durations, significant differences in the erythema score and wheal score could be observed between two groups (Figure 2). According to the sting-producing time scale, 3 of 30 of subjects felt stinging sensation after application, especially at test site A1. This stinging value at A1 was expressed as stingproducing score. This result suggests that there is a positive correlation with total clinical score (r ¼ 0.75, p ¼ 0.00). Biophysical parameters Differences in mean BF values (expressed as means  SD) between non-reactors and reactors were represented in Figure 3(a). After application removal, the mean BF values of reactors were significantly higher comparing to the nonreactors at each observation time. For each group, mean BF values in observation time course indicate a directly decreasing correlation. Figure 3(b) illustrated the change trends of BF, which were expressed as D means  SD. The increased surface BF of reactors was remarkably higher than that of non-reactors’ regardless of exposure duration. Interestingly however, the change of BF in A2 stage presented a peak type, this suggests at this duration of exposure, the difference value of blood flow between two groups was maximum and most significant. Biophysical parameters of erythema (a*, Oxy HbO and EI) and wheal (MI, Melanin and Scattering) were listed in Tables 1 and 2, respectively. Comparing the results of

Calculations and statistic The data were expressed as the means  SD. Analysis of results was performed with the procedure of SPSS 13.0 software (SPSS Inc., Chicago, IL). The t-test was used to assess differences between values referring to the two groups and a p value 50.05 was considered statistically significant. The Spearmann coefficient of rank was employed for correlation studies. The close level of significance was p ¼ 0.05 (two-tailed).

Results Questionnaire A total of 30 questionnaires were completed. There was no correlation between the questionnaire score and the clinical visual score, including total score (r ¼ 0.01, p ¼ 0.94), erythema score (r ¼ 0.02, p ¼ 0.91) and wheal score (r ¼ 0.032, p ¼ 0.866).

Figure 2. Clinical visual scoring for erythema and wheal in non-reactors and reactors with different exposure times (A1, A2, A3). Values (total scores in different observation times) represent the intensity of erythema and wheal according to the 0–3 scale. The high significances can be observed between two groups both in erythema and wheal. *p50.05, **p50.01.

Downloaded by [Texas A & M International University] at 20:10 05 November 2015

66

S. Y. Chen et al.

Cutan Ocul Toxicol, 2014; 33(1): 63–69

Figure 3. (a) The BF parameters. Comparison of BF values between non-reactors and reactors in different observation time by group of three exposure times. All values are expressed as means  SD. The high significances can be observed between two groups at each time point except baseline values. *p50.05, **p50.01. (b) Graphs showing the change trends of the BF in non-reactors and reactors in the order of different exposure times (A1, A2, A3) as three stages. Two dotted lines are used to distinguish these three stages. The values are expressed as means  SD. The obvious differences especially at the stage of A2 can be observed between two groups. *p50.05, **p50.01.

Table 1. Comparison of biophysical parameters related to erythema between non-reactors and reactors. BL Non-reactors

10 min Reactors

Non-reactors

30 min Reactors

Non-reactors

60 min Reactors

Non-reactors

Reactors

A1 EI 579.58  15.58 580.69  14.62 596.56  23.86 602.66  16.21 598.28  26.52 605.97  15.09 600.31  27.19 611.16  15.49 a* 8.44  1.36 8.54  1.19 10.70  2.89 13.98  1.39** 11.00  3.03 14.40  1.32** 11.09  2.81 14.01  1.62** OxyHbO 0.299  0.14 0.35  0.27 1.14  0.79 1.44  0.47 1.22  0.90 1.55  0.48 1.18  0.76 1.42  0.55 A2 EI 576.31  11.95 575.51  11.79 582.16  20.77 600.04  13.72* 586.33  22.39 601.36  13.98* 588.56  21.44 604.27  13.11* a* 8.14  1.19 8.00  1.11 8.82  2.28 12.57  1.68** 8.83  2.27 12.71  1.86** 9.34  2.20 12.68  1.85** OxyHbO 0.29  0.14 0.33  0.25 0.84  0.65 1.28  0.46** 0.87  0.63 1.37  0.35** 0.83  0.52 1.44  0.39** A3 EI 573.42  14.48 573.78  15.30 568.28  20.44 588.08  15.29** 570.09  22.81 591.73  16.24** 574.11  24.03 597.31  16.30** a* 7.98  1.35 8.18  1.38 7.74  1.99 9.99  1.57** 7.42  2.12 10.12  2.08** 7.95  2.22 11.00  1.86** OxyHbO 0.33  0.17 0.43  0.30 0.51  0.40 0.86  0.50** 0.41  0.31 0.97  0.45** 0.40  0.40 1.04  0.46** Values are obtained in different observation time points (including the baseline) by group of three exposure time points and expressed as means  SD. *p50.05, **p 50.01.

Table 2. Comparison of biophysical parameters related to wheal between non-reactors and reactors. BL Non-reactors

10 min Reactors

Non-reactors

30 min Reactors

Non-reactors

60 min Reactors

Non-reactors

Reactors

A1 MI 497.82  16.05 496.71  13.13 492.53  15.32 481.13  13.27* 492.93  14.38 481.18  13.05* 493.45  14.84 483.20  12.30* Melanin 1.72  0.32 1.71  0.22 1.56  0.43 1.29  0.41 1.57  0.39 1.32  0.42 1.62  0.41 1.40  0.39 Scattering 0.73  0.06 0.71  0.08 0.80  0.10 0.87  0.11 0.80  0.09 0.86  0.07 0.80  0.10 0.83  0.09 A2 MI 493.85  16.52 491.16  12.52 491.47  16.40 479.80  12.58* 492.49  17.16 479.36  13.14* 493.16  16.49 480.38  13.49* Melanin 1.69  0.31 1.71  0.24 1.62  0.34 1.34  0.44 1.59  0.40 1.34  0.36 1.68  0.36 1.34  0.40* Scattering 0.724  0.06 0.71  0.07 0.75  0.08 0.80  0.09 0.75  0.08 0.82  0.09 0.75  0.08 0.79  0.07 A3 MI 492.73  17.91 487.42  11.76 491.13  17.11 482.71  11.44 493.47  17.84 482.73  12.51 492.93  16.40 482.73  11.72 Melanin 1.69  0.36 1.68  0.24 1.66  0.35 1.60  0.29 1.69  0.37 1.58  0.36 1.70  0.33 1.53  0.32 Scattering 0.73  0.08 0.71  0.06 0.75  0.07 0.73  0.07 0.75  0.07 0.73  0.09 0.74  0.07 0.74  0.08 Values are obtained in different observation time points (including the baseline) by group of three exposure time points and expressed as means  SD. *p50.05, **p50.01.

DMSO used in skin angioneurotic reaction and permeability

Downloaded by [Texas A & M International University] at 20:10 05 November 2015

DOI: 10.3109/15569527.2013.821615

baseline suggest that there was no significant difference between reactor and non-reactor groups. After removal of 98% DMSO, the difference in reactors was significant higher than that of non-rectors for all of these three parameters in A2 and A3. Difference in reactors for a* values were significantly higher at A1. These results suggest that the inflammation in reactors was actually more intense. Furthermore, from A1 to A3, a clear tendency of a decrease of inflammation could be detected at each observation time. This trend of change is consistent with the results of BF values. With regard to the biophysical parameters of wheal, only the MI values showed significant difference between reactor and non-reactor groups in A1 and A2. At the last observation time (60 min) of A2, the Melanin values of non-reactors were significantly higher comparing to the reactors. There are positive correlations between the clinical visual score and erythema parameters regardless of exposure duration (except baseline values). There are negative correlations between the clinical visual score and wheal parameters detected in the A1 and A2 (Table 3). Ultrasound parameters Comparing the baseline values of depth and density of epidermis, there was no significance in A1, A2 and A3 between the two groups. But in A1, the density values were

67

remarkably related to sting-producing score (r ¼ 0.42, p ¼ 0.02) when compared with total visual score (r ¼ 0.32, p ¼ 0.09). This result is similar to that of the lactic acid sting test13, in which the subjects were regrouped according to the stingproducing score: if the score was 1 points, the subjects would be categorized as ‘‘non-stingers’’ (n ¼ 14); if this score was 2 points, the subjects were classed as high response ‘‘stingers’’ (n ¼ 16). Compared the baseline values of depth and density, the density values at A1 of stingers (126.88  11.11) was significantly lower than that of nonstingers’ (139.45  7.06; p ¼ 0.001). Figure 4 presented the ultrasound images of these two groups from A1 test site. The density of SC in non-stingers (Figure 4a) was obvious higher than stingers (Figure 4b).

Discussion Previous studies on evaluation of sensitive skin (SS) have used various chemical or product challenge protocols. The lactic acid sting test is the most widely used. However, it is concluded that the self-perceived response to lactic acid does not necessarily equate with other measures of SS, such as capsaicin and menthol13–15. In other words, people who have sensitive to lactic acid may be not sensitive to other chemicals, such as capsaicin and menthol13,14. In our study,

Table 3. Relationship between the clinical scores and biophysical parameters at different observation time points by group of three exposure times.

A1 10 min 30 min 60 min A2 10 min 30 min 60 min A3 10 min 30 min 60 min

BF

a*

0.78** 0.72** 0.59**

0.69** 0.69** 0.61**

0.86** 0.81** 0.71** 0.63** 0.59** 0.55**

EI

Oxy HbO

Deoxy Hb

Melanin

MI

Scattering

0.19 0.18 0.23

0.34 0.38* 0.44*

 0.08 0.13 0.06

0.44* 0.46* 0.46*

0.46* 0.50** 0.43*

0.48* 0.52* 0.41*

0.72** 0.76** 0.66**

0.48* 0.43* 0.47*

0.38* 0.49** 0.66**

0.17 0.17 0.13

0.45* 0.38* 0.53*

0.44* 0.46* 0.44*

0.39* 0.38* 0.34

0.62** 0.59** 0.64**

0.51** 0.48** 0.54**

0.59** 0.69** 0.67**

0.28 0.27 0.12

0.18 0.25 0.33

0.33 0.37 0.38

0.02 0.04 0.08

**Correlation is significant at the 0.01 level (two-tailed). *Correlation is significant at the 0.05 level (two-tailed). Values are expressed as correlation coefficient.

Figure 4. The 22 MHz ultrasound pictures for A1 test site of both two groups: (a) non-stingers showed an obvious high compactness image for SC while (b) stingers showed a much more thinner image.

68

S. Y. Chen et al.

the testing strategies focus primarily upon the stimulus response to DMSO which may reflect the unusual angioneurotic reaction of the skin to some extent. Agner8 claimed that the quantification of the DMSO-response could be a test for assessment of skin barrier function of SS, but our results have also shown that there was no correlation between self-perceived skin sensitivity (SPSS) score and clinical visual score or other parameters. Perhaps in this small sample group, intrinsic SS is not objectively assessed by questionnaires, since SS may be influenced by subjective factors such as the individual’s education level. After further analysis we conclude that the degree of SPSS could not represent the actual intensity of the DMSO-response for individuals.

Downloaded by [Texas A & M International University] at 20:10 05 November 2015

Angioneurotic reaction The DMSO response, which is usually represented as a temporary erythema or edema reactions, is probably mainly due to damage of the endothelium of small blood vessels with subsequent leakage of fluid. In dermatology, non-invasive instruments are widely used to characterize skin erythema and wheal reaction. The moorFLPI has been used to objectively measure the increase in superficial BF that results in the appearance of erythema16. Several studies have concluded that there is very good correlation between BF measurements and visual scoring of erythema17,18. This is in accordance with results from our studies. Superficial BF values and visual scoring all showed an obvious exposure duration-dependence and positive correlations. In our view, these data altogether not only confirm the results from previous studies1,2, but also prove that the criteria seen in Figure 1 should be simple, reliable, and indicative for visual assessment. According to the results of the study shown by Takiwaki19, quantification of the erythemas could be easily demonstrated by means of the Chromameter parameters a* and the hemoglobin or deoxyhemoglobin index of both the Mexamater and DRS, while the magnitude of the wheals could be expressed as topical melanin index. We observed in those study that after exposure to DMSO for 15 min (at A1), almost all the individuals in the reactor group had an obvious transient local edema with erythema surrounding2, while after exposure to DMSO for 5 min (at A3), only erythema was observed at test site without any wheal. We hypothesize that the strong stimulation would usually cause a visible local wheal as a major expression. Through weakening of the stimulation, the wheal reaction gradually disappears while erythema emerges as the main reaction. Combined with correlation analysis, we offer an explanation that as the exposure duration time proceed from long to short, or the magnitude of stimulation proceed from strong to weak, the coefficients of erythema parameters increase appearance at first, followed by decline. This is best exemplified at exposure duration of 10 min (at A2), while wheal parameters gradually decrease. Furthermore, we analyzed whether there is correlation between baseline values and clinical score, but found no such correlation. Thus, it is quite noticeable that the exposure time of 10 min should be the best exposure duration to detect the DMSO response, which induces two kinds of aforementioned physiological indications simultaneously.

Cutan Ocul Toxicol, 2014; 33(1): 63–69

All the parameters listed are useful and discriminative for assessment of dynamic change of skin color, which actually could objectively reflect the dynamic activity of cutaneous angioneurotic reactions20. After DMSO exposure for 10 min, the erythema parameters of reactors are significantly higher comparing to those of non-reactors. On the other hand, reactors generally have lower wheal indices than those of nonreactors. This observation suggests the angioneurotic reaction of the reactors is stronger than that of non-reactors. Combined with relevance analysis, a* value at the observation time of 30 min (r ¼ 0.760, p50.01) is the most informative to determine the differences among individuals’ angioneurotic reactions. Likewise, the best observation probes to evaluate the wheal response should be the Melanin and MI values at the observation time of 60 min (r ¼ 0.562, p50.05) and 30 min (r ¼ 0.460, p50.05), respectively. Altogether, results presented in the present study indicate that upon application of 98% DMSO for 10 min, biological parameters such as a*, melanin and MI value at specific observation times would be able to detect individuals with hyper-angioneurotic reactions to chemical stimulus. Our study indicates that the DMSO test, combined with new noninvasive methods, is a valuable and promising determinant for the evaluation of cutaneous angioneurotic reaction. Penetration Recent studies concluded high concentrations of DMSO interact with the skin lipids could lead the ceramide bilayers to undergo a phase transition from the gel phase to the liquid crystalline phase, which may facilitate the transport of active molecules across membranes21,22. Several studies2,21 concluded that this non-immunological immediate contact of urticaria induced by DMSO was due to a mere transient engorgement of the dermis with water. In fact however, multiple factors are involved. First and foremost is the rate of penetration of DMSO, which is dependent on the thickness and the integrity of the stratum corneum23. In the present study, comparison of the skin layer thickness is especially challenging because we could not find a correlation among the baseline values of epidermal depth, density and visual scoring, or other parameters. Furthermore, no significantly difference can be observed between the reactor and the non-reactor groups regardless of the DMSO exposure duration. Interestingly, if we divide the subjects according to the sting-producing score, high difference of density values between the stingers and non-stingers could be detected as it is shown in Figure 4. Combined with the correlation analysis, we have reasons to consider that the penetrative activity of DMSO is related to the thickness of individual skin in this study. Importantly, our results agree with many previous studies, which concluded that the adverse sensations induced by the chemical stimulations were closely related to the compactness and integrity of corneous layer2,23. In addition, it is confirmed to directly affect the sensory nerve terminals to receive surface stimulus24. In other words, if the stinging sensation appears earlier, to a certain extent that indicates the skin permeation is stronger. In the classical lactic acid sting test, this kind of phenomenon was also mentioned many times. Unfortunately, the limitation of our

DOI: 10.3109/15569527.2013.821615

study prevented us from defining and quantifying the skin permeability for DMSO. Further studies on the relationship between the skin thickness and penetrative activity remain to be done.

Acknowledgements The authors thank Mr Yan-Rui Gao, Miss Xiao-Ping Liu, Miss Shu-Yuan Li, Mrs Ying Cheng for their technical assistance during this study.

Downloaded by [Texas A & M International University] at 20:10 05 November 2015

Declaration of interest This work was supported by the Skin & Cosmetic Research Department, Shanghai Skin Disease Hospital, Shanghai, China.

References 1. Coverly J, Peters L, Whittle E, Basketter DA. Susceptibility to skin stinging, non-immunologic contact urticaria and acute skin irritation; is there a relationship? Contact Dermatitis 1998;38: 90–95 2. Frosch P, Duncan S, Kligman AM. Cutaneous biometries I, The response of human skin to dimethyl sulfoxide. Br J Dermatol 1980;102:263–274. 3. Barry BW, Bennett SL. Effect of penetration enhancers on the permeation of mannitol, hydrocortisone and progesterone through human skin. J Pharm Pharmacol 1987;39:535–546. 4. Lahti A, Maibach HI. An animal model for nonimmunologic contact urticaria. Toxicol Appl Pharmacol 1984;76:219–224. 5. Malten KE, Aried JD. Topical toxicity of various concentrations of DMSO recorded with impedance measurements and water vapour loss measurements. Contact Dermatitis 1978;4:80–92. 6. Farage MA. Perception of sensitive skin:changes in perceived severity and associations with environmental causes. Contact Dermatitis 2008;59:226–232. 7. Willis CM, Shaw S, De Lacharriere O, et al. Sensitive skin:an epidemiological study. Br J Dermatol 2001;145:258–263. 8. Agner T, Serup J. Quantification of the DMSO-response – a test for assessment of sensitive skin. Clin Exp Dermatol 1989;14: 214–217.

DMSO used in skin angioneurotic reaction and permeability

69

9. Diffey BL, Farr PM. Quantitative aspects of ultraviolet erythema. Clin Phys Physiol Meas 1991;12:311–325. 10. Westerhof W. CIE colorimetry. In: Serup J, Jemec G, eds. In vivo examination of the skin: a handbook of non-invasive methods. Boca Raton: CRC Press; 1995:385–397. 11. Vishwanath K, Chang K, Klein D, et al. Portable, fiber-based, diffuse reflection spectroscopy (DRS) systems for estimating tissue optical properties. Appl Spectrosc 2011;62:206–215. 12. Tenland T. On laser Doppler flowmetry. Lmkopmg Umversily, Medical Dissertations 1182; 1. 13. Robinson MK, Perkins MA. Evaluation of a quantitative clinical method for assessment of sensory skin irritation. Contact Dermatitis 2001;45:205–213. 14. Farage MA, Katsarou A, Maibach HI. Sensory, clinical and physiological factors in sensitive skin: a review. Contact Dermatitis 2006;55:1–14. 15. Marriott M, Holmes J, Peters L, et al. The complex problem of sensitive skin. Contact Dermatitis 2005;53:93–99. 16. Issachar N, Gall Y, Borrel MT, et al. Correlation between percutaneous penetration of methyl nicotinate and sensitive skin, using laser Doppler imaging. Contact Dermatitis 1998;39: 182–186. 17. Peker J, Whalbas W. Zur methodik der pH-messung der hautberflacae. Dermatologische Wochenschrift 1972;158: 572–578. 18. Berardesca E, Cespa M. Sodium lauryl sulphate induced cutaneous irritation. Contact Dermatitis 1988;19:136–140. 19. Takiwaki H, Serup J. Measurement of erythema and melanin indices. In: Serup J, Jemec G, eds. In vivo examination of the skin: a handbook of non-invasive methods. Boca Raton: CRC Press; 1995:377–384. 20. Clarys P, Alewaeters K. Skin color measurements: comparison between three instruments: the ChromameterÕ the DermaSpectrometerÕ and the MexameterÕ. Skin Res Technol 2000;6:230–238. 21. Notman R, den Otter WK. The permeability enhancing mechanism of DMSO in ceramide bilayers simulated by molecular dynamics. Biophys J 2007;93:2056–2068. 22. Kwak S, Lafleur M. Effect of dimethyl sulfoxide on the phase behavior of model stratum corneumlipid mixtures. Chem Phys Lipids 2009;161:11–21. 23. Olerud JE, Usui ML, Seckin D, et al. Neutral endopeptidase expression and distribution in human skin and wounds. J Invest Dermatol 1999;112:873–881. 24. Li Y, Hsieh ST, Chien HF, et al. Sensory and motor denervation influence epidermal thickness in rat foot glabrous skin. Exp Neurol 1997;147:452–462.

Dimethyl sulfoxide could be a useful probe to evaluate unusual skin angioneurotic reaction and epidermal permeability.

Dimethyl sulfoxide (DMSO) has been suggested as a traditional chemical probe for assessing skin susceptibility and barrier function. The purpose of th...
1MB Sizes 0 Downloads 0 Views