The effect of suramin on healing adult rodent dermal wounds.
Scarring, leading to impaired function, growth and appearance, is a major problem following many forms of surgery. Fetal wounds, unlike those in the adult, are characterised by a reduced growth factor profile and the absence of scar tissue (Whitby & Ferguson, 1991 a, b). The antiparasitic drug, suramin (a heparin analogue) inhibits binding of various growth factors (e.g. PDGF, bFGF, TGF-beta, EGF, IGF-I, IGF-II) to their receptors in vitro. These growth factors play key roles in wound healing. We attempted to manipulate experimentally their effectiveness in healing adult rat dermal incisional wounds by injecting suramin into the wound margins and comparing the resultant healing with an unmanipulated control wound in the same animal. Immunohistochemical staining demonstrated that, on d 7 and 14 postwounding, the numbers of monocytes/macrophages and blood vessels are markedly increased in suramin treated wounds compared with controls. Extracellular matrix deposition is lower, although very compact in organisation, lacking the usual honeycombed appearance of normal skin. These effects are widespread, being present not only in the wound area, but also in the surrounding tissue. No difference was detected at 70 d postwounding between the scars of suramin-treated and unmanipulated control wounds in the same animals. All such effects are increased slightly through the concentration range of 0.04-40 mg/kg suramin, with no significant change as concentrations greater than 40 mg/kg are applied. This suggests that suramin has marked effects on the early stages of wound healing, which plateau at 40 mg/kg concentration, but has no effect on scar formation.
Chamberlain
J
J
School of Biological Sciences, University of Manchester, UK.
Shah
M
M
Ferguson
M W
MW
D000279:Administration, Cutaneous; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002921:Cicatrix / Q000517:prevention & control; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000293:injuries*; D013498:Suramin / Q000009:adverse effects / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D014950:Wounds, Penetrating / Q000188:drug therapy* / Q000503:physiopathology
D005353:Fibronectins; D007797:Laminin; D013498:Suramin; D003094:Collagen