The Effect of Hydroxycamptothecin on Wound Healing Following Reduction of the Knee Intra-Articular Adhesion in Rabbits

Cell Biochem Biophys. 2015 Sep;73(1):221-7. doi: 10.1007/s12013-015-0593-9.

Abstract

Topical application of 10-hydroxycamptothecin (HCPT) can reduce intra-articular scar adhesion after knee surgery, but the effect of HCPT on wound healing has not yet been elucidated. The study investigates the effect of the topical application of HCPT on wound healing after knee surgery in rabbits. Forty New Zealand white rabbits were divided into five groups: 2.0, 1.0, 0.5, and 0.1 mg/ml HCPT groups and control group. Approximately 10 mm × 10 mm of the cortical bone was removed from both sides of the femoral condyle, and the underneath of the cancellous bone was exposed. HCPT in various concentrations or saline was applied to the decorticated sites. Two weeks after surgery, the intra-articular adhesion was evaluated by Masson's trichrome staining. The blood vessel density and the fibroblast counting were evaluated by hematoxylin-eosin staining. The Vascular endothelial growth factor (VEGF) expression was evaluated by immunohistochemical staining and mRNA measurement. The recovery of all rabbits was stable after surgery. Topical application of HCPT could reduce intra-articular adhesion after 2 weeks. The blood vessel density, the number of fibroblast, and the level of VEGF expression in 2.0 and 1.0 mg/ml HCPT groups were lower than those of 0.5 mg/ml HCPT group, 0.1 mg/ml HCPT group, and the control group. However, there was no difference in multiple parameters between 1.0 and 2.0 mg/ml HCPT groups. Topical application of HCPT could reduce intra-articular scar adhesion in rabbits, but HCPT with concentrations above 1.0 mg/ml may affect the wound healing process by inhibiting the angiogenesis and fibroblast proliferation.

Keywords: Hydroxycamptothecin; Intra-articular adhesion; Rabbit; Vascular endothelial growth factor; Wound healing.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Arthroplasty, Replacement, Knee / adverse effects*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Camptothecin / therapeutic use
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Knee Joint / surgery
  • Male
  • Postoperative Complications
  • Rabbits
  • Tissue Adhesions / drug therapy*
  • Tissue Adhesions / etiology
  • Tissue Adhesions / prevention & control
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / drug effects*

Substances

  • Antineoplastic Agents, Phytogenic
  • Vascular Endothelial Growth Factor A
  • 10-hydroxycamptothecin
  • Camptothecin