Effects of Albumin Infusion on Serum Levels of Albumin, Proinflammatory Cytokines (TNF-α, IL-1, and IL-6), CRP, and MMP-8; Tissue Expression of EGRF, ERK1, ERK2, TGF-β, Collagen, and MMP-8; and Wound Healing in Sprague Dawley Rats

In this study, we sought to determine the roles of albumin in wound healing, which is infused both pre- and postoperatively in malnourished patients presenting with hypoalbuminemia. For the purposes of the study, we used 25 male Sprague Dawley rats of predetermined weight and age, which were initially maintained in a standard environment and fed the same diet for 7 days prior to being segregated into one of the following five groups: A, control, normal protein feed (20% casein); B, hypoalbuminemia, 25% rat albumin infusion prior to surgery; C, hypoalbuminemia, normal protein feed (20% casein); D, hypoalbuminemia, 25% rat albumin infusion after surgery; and E, hypoalbuminemia, low-protein feed (casein 2%). The animals in all five groups were subjected to four deep incisions in their dorsal muscle fascia. On days 1, 3, 5, and 7 after surgery, ELISA was used to determine serum levels of TNF-α, IL-1, IL-6, CRP, and MMP-8, whereas immunohistochemistry was used to determine the tissue expression of EGFR, ERK1, ERK2, TGF-β, collagen, and MMP-8. Significant reductions in serum levels of TNF-α, IL-1, and CRP were detected in the groups receiving albumin infusion and the high-casein diet (P < 0.05). The administration of albumin and a high-casein diet also increased the tissue expression of EGFR, ERK1, ERK2, TGF-β, and collagen and decreased that of MMP-8 relative to the hypoalbuminemia control (P < 0.05). We propose that the administration of albumin promoted NF-κB signaling which, in turn, induced the transduction and transcription of factors involved in wound healing. Albumin infusion and dietary proteins play vital roles in accelerating the wound healing process, as they can contribute to correcting the hypoalbuminemic state. These findings provide insights that will contribute to our understanding of wound healing, particularly in malnourished patients.

[1]  A. Hutcheon,et al.  Epidermal Growth Factor Stimulates Transforming Growth Factor-Beta Receptor Type II Expression In Corneal Epithelial Cells , 2019, Scientific Reports.

[2]  Robert R. Wolfe,et al.  Hypoalbuminemia: Pathogenesis and Clinical Significance , 2018, JPEN. Journal of parenteral and enteral nutrition.

[3]  Mikaël M. Martino,et al.  Immune Regulation of Skin Wound Healing: Mechanisms and Novel Therapeutic Targets. , 2018, Advances in wound care.

[4]  D. Chae,et al.  Hypoalbuminemia at admission predicts the development of acute kidney injury in hospitalized patients: A retrospective cohort study , 2017, PloS one.

[5]  Shishira S. Bharadwaj,et al.  Malnutrition: laboratory markers vs nutritional assessment , 2016, Gastroenterology report.

[6]  E. O’Toole,et al.  Metalloproteinases and Wound Healing. , 2015, Advances in wound care.

[7]  Chung-Tien Lin,et al.  ERK1/2 Activation Regulates the Wound Healing Process of Rabbit Corneal Endothelial Cells , 2009, Current eye research.

[8]  D. Tritchler,et al.  Albumin activates ERK via EGF receptor in human renal epithelial cells. , 2005, Journal of the American Society of Nephrology : JASN.

[9]  S. Yuspa,et al.  EGFR enhances early healing after cutaneous incisional wounding. , 2004, The Journal of investigative dermatology.

[10]  J. Klarlund,et al.  Wounding Induces Motility in Sheets of Corneal Epithelial Cells through Loss of Spatial Constraints , 2004, Journal of Biological Chemistry.

[11]  P. Brecher,et al.  Temporal Control of NF-κB Activation by ERK Differentially Regulates Interleukin-1β-induced Gene Expression* , 2004, Journal of Biological Chemistry.

[12]  K. Chan,et al.  Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo. , 2003, The Journal of clinical investigation.

[13]  T. Hunter,et al.  Nuclear export of phosphorylated C/EBPβ mediates the inhibition of albumin expression by TNF‐α , 2001 .

[14]  A. M. C. Manzano Hypoalbuminemia in dialysis. Is it a marker for malnutrition or inflammation , 2001 .

[15]  M. Luster,et al.  Impaired cutaneous wound healing in interleukin‐6‐deficient and immunosuppressed mice , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  I. K. Cohen,et al.  MMP-8 is the predominant collagenase in healing wounds and nonhealing ulcers. , 1999, The Journal of surgical research.

[17]  D. Straus,et al.  Effect of amino acid limitation on the expression of 19 genes in rat hepatoma cells , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  J. Doweiko,et al.  Reviews: Role of Albumin in Human Physiology and Pathophysiology , 1991 .

[19]  L. Moldawer,et al.  The biologic characteristics of cytokines and their implication in surgical injury. , 1990, Surgery, gynecology & obstetrics.

[20]  Y. Fujii‐Kuriyama,et al.  Low protein--high energy diet induces repressed transcription of albumin mRNA in rat liver. , 1987, The Journal of nutrition.

[21]  G. Hill,et al.  Impaired wound healing in surgical patients with varying degrees of malnutrition. , 1986, JPEN. Journal of parenteral and enteral nutrition.

[22]  Luiz Antonio Bettinelli,et al.  Prevalencia de hipoalbuminemia y aspectos nutricionales en ancianos hospitalizados , 2016 .

[23]  C. Pollock,et al.  Protein malnutrition and hypoalbuminemia as predictors of vascular events and mortality in ESRD. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[24]  • Epidermis,et al.  WOUND healing. , 1959, The Medical journal of Australia.