The effects of melatonin and caffeic acid phenethyl ester (CAPE) on fracture healing under ischemic conditions

Acta Orthop Traumatol Turc. 2014;48(3):339-45. doi: 10.3944/AOTT.2014.3244.


Objective: The aim of this study was to investigate the effects of antioxidant molecules melatonin and caffeic acid phenethyl ester (CAPE) on fracture healing under ischemic conditions.

Methods: A right tibia fracture was created and fixed with an intramedullary pin in forty four male Wistar-albino rats. The rats were then randomly allocated to fracture, fracture-ischemia, fracture- ischemia-melatonin, and fracture-ischemia-CAPE groups. Ischemia was created by clamping femoral arteries four and a half hours. Animals were killed and radiographic, histological and biomechanical evaluation was performed sixth week after surgery.

Results: The radiological and histological scores of the fracture-ischemia-CAPE group were significantly better than the fracture- ischemia group at 6th week follow-up. Complete radiographical and histological healing of all fractures was detected in all groups. There was a significant difference between the maximum fracture force between the groups (fracture-ischemia<fracture-ischemia-melatonin<fracture<fracture-ischemia-CAPE) (p<0.005). Although difference was not statistically significant between fracture and fracture-ischemia-CAPE groups, all other groups revealed statistically significant difference with respect to toughness (N/mm). Fracture-ischemia group revealed the lowest toughness.

Conclusion: Ischemia adversely affects the fracture healing of rat tibias. Melatonin and CAPE eradicate adverse effects of ischemia. Possible adverse effects of ischemia on fracture healing can be eradicated with melatonin and CAPE in patients with tibia fractures associated with vascular injury or compartment syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Caffeic Acids / pharmacology*
  • Disease Models, Animal
  • Fracture Fixation, Intramedullary*
  • Fracture Healing / drug effects*
  • Ischemia*
  • Male
  • Melatonin / pharmacology*
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / pharmacology
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Tibial Fractures / therapy*


  • Antioxidants
  • Caffeic Acids
  • caffeic acid phenethyl ester
  • Melatonin
  • Phenylethyl Alcohol