Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing

J Biomed Opt. 2015 May;20(5):051022. doi: 10.1117/1.JBO.20.5.051022.


Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Cell Line, Tumor
  • Cell Proliferation
  • Cobamides / chemistry*
  • Cyanides / chemistry
  • Cyclic GMP / chemistry
  • Electron Transport
  • Electron Transport Complex IV / chemistry
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Hot Temperature
  • Humans
  • Light
  • Low-Level Light Therapy*
  • Nitric Oxide / chemistry
  • Nitrogen / chemistry
  • Oxygen Consumption
  • Photochemistry
  • Reactive Oxygen Species
  • Signal Transduction
  • Sodium Azide / chemistry
  • Wound Healing*


  • Cobamides
  • Cyanides
  • Reactive Oxygen Species
  • cobinamide
  • Nitric Oxide
  • Adenosine Triphosphate
  • Sodium Azide
  • Electron Transport Complex IV
  • Extracellular Signal-Regulated MAP Kinases
  • Cyclic GMP
  • Nitrogen