Topically applied S-nitrosothiol-containing hydrogels as experimental and pharmacological nitric oxide donors in human skin
Topically applied S-nitrosothiol-containing hydrogels as experimental and pharmacological nitric oxide donors in human skin
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DOI：
10.1111/j.1365-2133.2004.06213.x
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发表时间：
2004-11-01
影响因子：
10.3
通讯作者：
Weller, R
中科院分区：
文献类型：
--
作者：
Seabra, AB;Fitzpatrick, A;Weller, R
一氧化氮（NO）在皮肤中具有广泛的功能，局部一氧化氮供体有几种潜在的临床应用。然而，目前可用的供体要么在皮肤表面不稳定，释放低浓度的一氧化氮，要么作用时间短。内源性s -亚硝基硫醇（RSNOs）在体内储存和运输NO，并可作为NO的外源性来源。目的研究两种RSNO （s -亚硝基谷胱甘肽，GSNO）和s -亚硝基-n -乙酰半胱氨酸，SNAC)在易涂水凝胶中的体内外化学行为，并探讨其与皮肤亚硝酸盐浓度的关系。评估GSNO和SNAC作为临床研究和潜在治疗药物的生物学有效NO供体的适用性。方法/患者将GSNO （0.3 mol g(-1)）和SNAC （0.6 mol g(-1)）掺入Synperonic F-127水凝胶中（Uniquema, Belgium）。37℃分光光度法测定了其体外分解动力学。将含rsno的水凝胶涂于8名受试者的前臂皮肤。用激光多普勒测量4名受试者在应用NO供体后3 h的血流，同时在微透析液中测量皮肤亚硝酸盐。结果平均血流量峰值为250。血流量< 250时，皮肤亚硝酸盐与血流量密切相关，可用公式定义：血流量=（亚硝酸盐浓度x 0.66） + 120, （P = 0.013）。在较高的血流量有一个矛盾的下降，真皮亚硝酸盐浓度。结论外用一氧化氮一氧化氮能在人体皮肤上持续、有效地释放一氧化氮，这比目前可用的外用一氧化氮供体更有优势。皮肤亚硝酸盐浓度-一氧化氮的氧化产物-在低和中等血流量水平下与血流量直接相关。在高水平的血流量下，皮肤亚硝酸盐减少，这被认为是由于血液清除能力的增加。
Background Nitric oxide (NO) has a wide range of functions in the skin, and topical NO donors have several potential clinical applications. However, currently available donors are either unstable on the skin surface, release low concentrations of NO, or have a short duration of action. Endogenous S-nitrosothiols (RSNOs) store and transport NO within the body and can be used as exogenous sources of NO.Objectives To study in vitro and in vivo the chemical and biological behaviour of two RSNO species, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC), in an easily applied hydrogel, and to correlate dermal nitrite concentration with erythema following application of the RSNOs. To assess the suitability of GSNO and SNAC as biologically effective NO donors for clinical research and as potential therapeutic agents.Methods/patients GSNO (0.3 mol g(-1)) and SNAC (0.6 mol g(-1)) were incorporated in Synperonic F-127 hydrogels (Uniquema, Belgium). The in vitro kinetics of decomposition were measured by spectrophotometry at 37 degreesC. The RSNO-containing hydrogels were applied to the forearm skin of eight subjects. Blood flow was measured by laser Doppler for 3 h following application of NO donors and dermal nitrite simultaneously measured in microdialysate in four subjects.Results The mean peak blood flow achieved was 250. At blood flow values of < 250, dermal nitrite correlated closely with blood flow and could be defined by the equation: blood flow = (nitrite concentration x 0.66) + 120, (P = 0.013). At higher blood flows there was a paradoxical fall in dermal nitrite concentration.Conclusions Topical RSNOs produce a consistent, sustained and biologically effective release of NO on human skin in vivo, which offers advantages over currently available topical NO donors. Dermal nitrite concentration-the oxidation product of NO-is directly correlated with blood flow at low and moderate levels of blood flow. At high levels of blood flow, there is a reduction in dermal nitrite, which is presumed to be due to increased blood scavenging.