Hyaluronidase modulates inflammatory response and accelerates the cutaneous wound healing.
Hyaluronidases are enzymes that degrade hyaluronan an important constituent of the extracellular matrix. They have been used as a spreading agent, improving the absorption of drugs and facilitating the subcutaneous infusion of fluids. Here, we investigated the influence of bovine testes hyaluronidase (HYAL) during cutaneous wound healing in in vitro and in vivo assays. We demonstrated in the wound scratch assay that HYAL increased the migration and proliferation of fibroblasts in vitro at low concentration, e.g. 0.1 U HYAL enhanced the cell number by 20%. HYAL presented faster and higher reepithelialization in in vivo full-thickness excisional wounds generated on adult Wistar rats back skin already in the early phase at 2nd day post operatory compared to vehicle-control group. Wound closured area observed in the 16 U and 32 U HYAL treated rats reached 38% and 46% compared to 19% in the controls, respectively. Histological and biochemical analyses supported the clinical observations and showed that HYAL treated wounds exhibited increased granulation tissue, diminished edema formation and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines, growth factor and eicosanoids mediators. Moreover, HYAL increased gene expression of peroxisome proliferator-activated receptors (PPAR) γ and PPAR β/δ, the collagen content in the early stages of healing processes as well as angiogenesis. Altogether these data revealed that HYAL accelerates wound healing processes and might be beneficial for treating wound disorders.
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil; Departamento de Farmácia, Universidade de Vila Velha, Vila Velha, Espirito Santo, Brazil.
Marcio
M
Fronza
Departamento de Clínica Médica, Divisão de Dermatologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Guilherme F
GF
Caetano
Departamento de Clínica Médica, Divisão de Dermatologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Marcel N
MN
Leite
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Claudia S
CS
Bitencourt
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Francisco W G
FW
Paula-Silva
Departamento de Clínica Médica, Divisão de Dermatologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Thiago A M
TA
Andrade
Departamento de Clínica Médica, Divisão de Dermatologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Marco A C
MA
Frade
Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany.
Irmgard
I
Merfort
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Lúcia H
LH
Faccioli
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D006097:Granulation Tissue / Q000187:drug effects / Q000254:growth & development; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology*; D008297:Male; D051379:Mice; D047492:Peroxisome Proliferator-Activated Receptors / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012879:Skin Physiological Phenomena; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D016207:Cytokines; D015777:Eicosanoids; D047492:Peroxisome Proliferator-Activated Receptors; D003094:Collagen; D006821:Hyaluronoglucosaminidase