The role of nutrition during the early inflammatory stage of cutaneous wound healing

 
 
 
 

The role of nutrition during the early inflammatory stage of cutaneous wound healing

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dc.contributor.advisor Bray, Tammy M en_US
dc.contributor.author Lim, Yunsook en_US
dc.date.accessioned 2008-07-07T19:25:11Z
dc.date.available 2008-07-07T19:25:11Z
dc.date.created 2003 en_US
dc.date.issued 2008-07-07T19:25:11Z
dc.identifier.uri http://rave.ohiolink.edu/etdc/view?acc_num=osu1040419380 en_US
dc.identifier.uri http://hdl.handle.net/2374.OX/7833
dc.description Although various factors are involved in the wound healing process, malnutrition may be a major factor that can lead to tissue damage and delay wound healing. It is well known that malnutrition triggers compromised immune functions and decreased antioxidant defense in many studies. Moreover, immune response and antioxidant defense are critical facets of the inflammatory stage that can be the rate-limiting step of later stages of wound healing. Thus, nutritional modulation of immune function and antioxidant status may play a crucial role in the control and regulation of wound healing. Reactive oxygen species (ROS) and proinflammatory cytokines produced by immune cells during inflammation activate NFkB, a redox sensitive transcription factor that induces expression of immunoregulatory genes such as chemokines and cytokines during the inflammatory stage. NFkB activation and proinflammatory cytokine production play key roles in regulating wound healing. Notably, protein energy malnutrition (PEM) and zinc deficiency are well-known health problems associated with delayed wound healing. N-acetyl cysteine (NAC) supplementation in PEM may help wound healing by enhancing immune response and antioxidant defense. Zinc supplementation may also increase immune function and antioxidant defense. Therefore, this dissertation was focused upon the role of nutrition and ROS in wound closure and the effect of nutritional supplementation on immune response and antioxidant defense at cellular and molecular levels during the early inflammatory stage of cutaneous wound healing. We have hypothesized that malnutrition delays cutaneous wound closure due to decreased immune response and antioxidant defense. Furthermore, we propose that nutritional supplementation will restore immune function and antioxidant defense in the inflammatory stage during cutaneous wound healing. To test these hypotheses, we have: i) investigated the effects of PEM and the role of ROS using CuZnSOD transgenic mice to determine if malnutrition or ROS affect cutaneous wound healing; ii) examined the role of dietary supplementation of NAC on wound closure and gene expression of pro-inflammatory cytokines (IL-1b and TNF-a) and IkB (indirect measurement of NFkB activation) during the early inflammatory stage in PEM mice; and iii) investigated the role of dietary zinc on wound closure and gene expression of IL-1b, TNF-a and IkB. The results of these experiments demonstrated that PEM impaired wound healing, possibly due to delayed neutrophil infiltration and decreased gene expression of IkB, IL-1b and TNF-a. However, NAC supplementation restored neutrophil response and normalized gene expression of IkB, IL-1b and TNF-a in the early inflammatory stage of cutaneous wound healing. In addition, we found that zinc deficiency delayed wound closure. Notably, we also found that zinc supplementation at 500 ppm accelerated neutrophil infiltration, increased expression of IkB and enhanced wound closure. However, mega dose zinc supplementation at 1000 ppm (20 times higher than that of a control diet) delayed neutrophil infiltration, decreased IkB levels and delayed normal wound closure. In conclusion, this study provides further evidence of the critical role of nutrition in wound healing. More importantly, results from these experiments demonstrated that NAC supplementation provides an effective intervention strategy to enhance wound healing in PEM patients. However, we have also demonstrated that supplementation strategies must be approached judiciously, as our results show that whereas zinc supplementation at 500 ppm may enhance wound healing, zinc supplementation at 1000 ppm significantly delays wound healing. en_US
dc.format application/pdf en_US
dc.format 140p. en_US
dc.rights unrestricted en_US
dc.rights Copyright and permissions information available at the source archive en_US
dc.subject wound healing. PEM en_US
dc.subject zinc en_US
dc.subject NF-kB en_US
dc.subject proinflammatory cytokine en_US
dc.subject NAC en_US
dc.title The role of nutrition during the early inflammatory stage of cutaneous wound healing en_US
dc.type Electronic Thesis or Dissertation en_US
dc.degree.name PhD en_US
dc.degree.level doctoral en_US
dc.degree.discipline Ohio State University Nutrition en_US
dc.degree.grantor Ohio State University en_US
dc.contributor.publisher Ohio State University / OhioLINK en_US

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