piperidines and Wounds--Penetrating

It is a major interest in the field of hematopoietic stem cell transplantation to reduce scarring of healing wounds with overdeposition of collagen due to radiation injury or graft-versus-host disease. Halofuginone (HF) inhibits collagen alpha1(I) gene expression and overdeposition of collagen. We examined the effect of HF on the healing of full-depth incision wounds inflicted in normal skin or skin areas compromised by local preirradiation with 18 Gy. Preirradiation significantly decreased the tensile strength of the healing wounds at day 14 (by approximately 60%, p < 0.0001). In contrast, HF treatment did not significantly decrease the strength of wounds inflicted in both normal and preirradiated skin. Histological evaluation revealed that HF induced moderate thinning of the dermis accompanied by elevated thickness of the epidermis and enhanced rejoining of subdermal muscles in the wound area. HF only minimally reduced total collagen deposition in both groups, with minor changes in the level of more matured fibrillar collagen network. Our study demonstrates that HF does not significantly affect wound strength. This encourages the possible use of HF as an antifibrotic agent with minimal complications for post-hematopoietic stem cell transplantation complications including radiation toxicity and graft-versus-host disease.

Topics: Animals; Cicatrix; Collagen Type I; Drug Evaluation, Preclinical; Hematopoietic Stem Cell Transplantation; Mice; Mice, Inbred C3H; Piperidines; Quinazolinones; Skin; Specific Pathogen-Free Organisms; Tensile Strength; Transplantation Conditioning; Wound Healing; Wounds, Penetrating

The synthetic immunomodulators muramyl dipeptide (MDP), thymopoietin pentapeptide (TP5), and CP-46,665 were examined for their effects on wound healing in mice. We found no differences in wound disruption strength between immunomodulator-treated animals and saline controls on days 11, 14, and 21. The only exception was with high-dose CP-46,665, which produced weakened wounds on day 14 (p less than 0.05) and 21 (p less than 0.01). CP-46,665 was further studied by injecting high and low doses 48 hours before or after wounding. No differences were seen for these groups compared to controls at 11 and 21 days. Finally, to simulate a common clinical situation, mice were subjected to a 10% total body surface area (TBSA) burn to the right paraspinal region. Twenty-four hours later, a left paraspinal incision was performed with simultaneous injection of saline, Corynebacterium parvum (C. parvum), or low-dose TP-5, MDP, or CP-46,665. At 11 days, no detriment in wound healing was found for burned control or any of the immunomodulator-treated animals except in the C. parvum-treated mice, with significantly weakened skin strips (p less than 0.001). While C. parvum may be detrimental to wound healing, the synthetic modulators tested appear to have little effect on wound healing.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Burns; Male; Mice; Mice, Inbred Strains; Peptide Fragments; Piperidines; Propionibacterium acnes; Skin; Thymopentin; Thymopoietins; Wound Healing; Wounds, Penetrating