Pentoxifylline Accelerates Wound Healing Process by Modulating Gene Expression of MMP-1, MMP-3, and TIMP-1 in Normoglycemic Rats

J Invest Surg. 2015;28(4):196-201. doi: 10.3109/08941939.2014.1002642. Epub 2015 Jun 18.


Background: Although numerous recent advances in wound healing have highlighted the importance of adjunct therapies in maximizing healing potential, abnormal wound healing continues to cause significant expense, morbidity, and mortality.

Objective: This study examines the effects of pentoxifylline (PTX) on wound healing.

Hypothesis: We are expecting that PTX administration can increase biomechanical parameters and modulate matrix metalloproteinaseses-1 (MMP-1) and MMP-3, and matrix metalloproteinase inhibitor-1 (TIMP-1) in normoglycemic (NG) rat model of wound healing.

Methods: Each rat received an identical wound from a full-thickness incision on its back. Experimental rats received systemic administration of PTX. All rats underwent examinations for biomechanical and polymerase chain reaction(PCR) analysis. Maximum stress and energy absorption were calculated as the biomechanical examinations. Expressions of MMP-1, MMP-3 and TIMP-1 genes were evaluated semi-quantitatively by reverse transcriptional (RT)-PCR.

Results: PTX significantly improved biomechanical parameters. Quantification of MMP-1, MMP-3, and TIMP-1 showed that PTX significantly reduced gene expressions of MMP-1 and MMP-3. There was a significant increase in TIMP-1 gene expression.

Conclusion: Systemic administration of PTX significantly accelerated the wound healing process in NG rats.

Keywords: biomechanical evaluation; normoglycemic rats; pentoxifylline; reverse transcriptional polymerase chain reaction; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Blood Glucose / analysis
  • Drug Evaluation, Preclinical
  • Enzyme Induction / drug effects
  • Gene Expression Regulation / drug effects*
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 3 / biosynthesis*
  • Matrix Metalloproteinase 3 / genetics
  • Pentoxifylline / pharmacology
  • Pentoxifylline / therapeutic use*
  • Rats
  • Rats, Wistar
  • Skin / injuries
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Wound Healing / drug effects*


  • Blood Glucose
  • TIMP1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 3
  • MMP1 protein, rat
  • Matrix Metalloproteinase 1
  • Pentoxifylline