Abstract
N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing.
Highlights
Wound healing involves a complex series of interactions between different cell types, cytokine mediators, and the extracellular matrix (ECM)
We examined the dose responsive effects of Nac on GSH and matrix metalloproteinases (MMPs)-1 activities, phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos, Jun and extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) expressions, and burn wound healing in rats
We examined the proteins involved in regulating the expression of MMP-1
Summary
Wound healing involves a complex series of interactions between different cell types, cytokine mediators, and the extracellular matrix (ECM). There are three or four major stages of wound healing: inflammation, proliferation, matrix deposition and remodeling [1,2]. Thermal trauma is an acute wound, where substantial areas of skin can be damaged, often without the possibility of skin regeneration. Burns and scalds can sometimes result in rapid, extensive, deep wounds that cannot be successfully treated with common techniques, and can lead to death [3]. Burn injuries incur a significant cost to health care systems worldwide. 1.2 million people sustain burn injuries each year and about 100,000 of these cases require hospitalization.
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