Topical N-Acetylcysteine Accelerates Wound Healing in Vitro and in Vivo via the PKC/Stat3 Pathway

Tsai, Min-Ling; Huang, Hui-Pei; Hsu, Jeng-Dong; Lai, Yung‐Rung; Hsiao, Yu‐Ping; Lu, Fung‐Jou; Chang, Horng-Rong

doi:10.3390/ijms15057563

Cited by 60 publications

(60 citation statements)

References 30 publications

(31 reference statements)

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“…Consistent with our observation, NAC has also been observed to promote cellular proliferation in adipose-derived stem cells, which hold great promise for wound repair and regeneration [16]. In addition, a recent study has also reported that NAC enhanced cellular proliferation as well as scratch wounding healing in CCD966SK cells (human skin fibroblast cell line) [1]. We also observed that increased cellular proliferation induced by NAC during wound healing was paralleled with increased levels of MnSOD protein expression and activity.…”

Section: Discussionsupporting

confidence: 88%

“…In addition, the effect of NAC on extracellular matrix (ECM) remodeling during wound healing has also been reported. Topical NAC administration has been demonstrated to accelerate burn wound healing through induction of collagenous expression of matrixmetalloproteinase-1 (MMP-1) via protein kinase C (PKC) signaling pathway, which has been implicated in pathologies involving ECM remodeling [1]. …”

Section: Discussionmentioning

confidence: 99%

“…N-acetyl-cysteine (NAC) is an antioxidant that has been previously reported to improve different types of wound healing [1-4]. NAC is the acetylated precursor of both the amino acid L-cysteine and reduced glutathione (GSH) [5].…”

Section: Introductionmentioning

confidence: 99%

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N-acetyl-l-cysteine increases MnSOD activity and enhances the recruitment of quiescent human fibroblasts to the proliferation cycle during wound healing

et al. 2015

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Background The rebuilding of the connective tissue during wound healing requires the recruitment of fibroblasts to the wound area as well as reentry of quiescent fibroblasts to the proliferative cycle. Whether this process can be modulated by a small molecular weight thiol antioxidant N-acetyl-L-cysteine (NAC) was tested in normal human skin fibroblasts (NHFs) in this study. Methods and Results By using a uni-directional wound healing assay, NAC treated cells demonstrated a decreased migration rate but increased number of proliferating cells recruited into the wound area post wounding. Fifteen day quiescent control and NAC treated NHFs were re-plated at a lower density and cell numbers counted at different days post-plating. Interestingly, NAC treated cells exhibited increased cellular proliferation indicated by both decreased cell population doubling time and increased S phase cells. NAC treated cells demonstrated decreased steady state levels of reactive oxygen species as well as increased protein and activity levels of manganese superoxide dismutase (MnSOD). NAC treatment failed to induce proliferation in quiescent cells lacking MnSOD expression. Conclusions These results demonstrate that NAC enhanced the recruitment of quiescent NHFs into proliferation cycle during wound healing. Our results also suggest that the wound healing properties of NAC might be due to its ability to induce and enhance MnSOD expression and activity. Altogether, these findings suggest NAC might be potentially developed as a dietary intervention to improve tissue injury in animals and humans.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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N-acetyl-l-cysteine increases MnSOD activity and enhances the recruitment of quiescent human fibroblasts to the proliferation cycle during wound healing

et al. 2015

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“…21 MinLing Tsai et al reported that the topical administration of 3% NAC was significantly effective on the cell proliferation, migration, scratch wound healing, and collagenous expression of MMP-1 via the PKC/ Stat3 signaling pathway. 9 In addition, topical NAC 8% eye drops have also been reported to improve the initial treatment of experimental alkali corneal burns. 22 In our study, better wound healing ratios and epithelialization ratios were obtained in the NAC group than in the control group, and the mean fibrosis score was significantly higher in the NAC group than in the control group.…”

Section: Discussionmentioning

confidence: 99%

“…This process can be facilitated by a number of natural or artificial agents. 9 However, the wound healing process can be interrupted by a number of factors, which may impair 1 or more stages of the process and thus lead to inappropriate or failed tissue repair. Failed processes of wound healing lead to large amounts of health care expenses, which are estimated to exceed $3 billion per year.…”

Section: Discussionmentioning

confidence: 99%

Topical N-Acetylcysteine Improves Wound Healing Comparable to Dexpanthenol: An Experimental Study

Oğuz

Uslukaya

Alabalık

et al. 2015

International Surgery

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In this study, we aimed to compare the effects of dexpanthenol and N-acetylcysteine on wound healing. The wound healing process is a multifaceted sequence of activities associated with tissue restoration process. A number of investigations and clinical studies have been performed to determine new approaches for the improvement of wound healing. A total of 30 rats were divided into 3 equal groups. A linear 2-cm incision was made in the rats' skin. No treatment was administered in the first (control) group. Dexpanthenol cream was administered to the rats in the second group and 3% Nacetylcysteine cream was administered to the rats in the third group. The wound areas of all of the rats were measured on certain days. On the 21st day, all wounds were excised and histologically evaluated. The epithelialization and granulation rates between the groups were revealed to be similar in microscopic evaluations. Although the fibrosis was remarkable in the control group as compared with the other groups, it was similar in Nacetylcysteine and dexpanthenol groups. Angiogenesis rate was remarkable in the Nacetylcysteine group compared with the others. In multiple-comparison analysis, Dexpanthenol and N-acetylcysteine groups had similar results in terms of wound healing rates (P , 0.05), which were both higher than in the control group (P . 0.05). The efficacy of N-acetylcysteine in wound healing is comparable to dexpanthenol, and both substances can be used to improve wound healing.

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Sustained release of N‐acetylcysteine by sandwich structured polycaprolactone/collagen scaffolds for wound healing

Hou

Chen

Liu

et al. 2019

J Biomedical Materials Res

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PCL (poly‐caprolactone) nanofibers have good biocompatibility and high porosity, which are usually utilized for application in wound dressings. However, wound healing could be hindered by the overproduction of reactive oxygen species (ROS) and different factors. Pure nanofibers cannot satisfy these requirements of wound healing. N‐acetylcysteine (NAC), as an antioxidant, meets the requirements for wound healing by resisting the overproduction of ROS and by promoting angiogenesis and maturation of the epidermis. In this study, we prepared a sandwich structured PCL‐Col/NAC scaffold using the molding method, which consisted of PCL nanofibers at the core and NAC‐loaded collagen on both sides. The hydroscopicity and tensile modulus of PCL‐Col/NAC scaffolds showed best performance of these properties among groups. Meanwhile, the drug release profiles of PCL‐Col/NAC scaffolds were investigated using the HPLC method and the results suggested a sustained drug release of NAC for PCL‐Col/NAC scaffolds. In addition, PCL‐Col/NAC scaffolds presented better properties than the control groups in cell migration and proliferation. The in vivo wound healing therapy effect was studied using an oval (2 × 1 cm) full‐thickness skin defect wound model for SD rats. After 21 days, gross view and histological analysis showed a favorable beneficial therapeutic effect as well as better epidermal maturation compared with the control groups. CD31 immunohistology results revealed relatively more new vessels in the PCL‐Col/NAC group than the control groups. This study developed novel PCL‐Col/NAC scaffolds with an excellent hydroscopicity, tensile modulus and the ability to promote epidermal maturation and angiogenesis, demonstrating its promising potential in wound healing treatment. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

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Topical N-Acetylcysteine Accelerates Wound Healing in Vitro and in Vivo via the PKC/Stat3 Pathway

Cited by 60 publications

References 30 publications

N-acetyl-l-cysteine increases MnSOD activity and enhances the recruitment of quiescent human fibroblasts to the proliferation cycle during wound healing

N-acetyl-l-cysteine increases MnSOD activity and enhances the recruitment of quiescent human fibroblasts to the proliferation cycle during wound healing

Topical N-Acetylcysteine Improves Wound Healing Comparable to Dexpanthenol: An Experimental Study

Sustained release of N‐acetylcysteine by sandwich structured polycaprolactone/collagen scaffolds for wound healing

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