Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats.
Substance P (SP) is known to stimulate angiogenesis, fibroblasts proliferation and expressions of cytokines and growth factors involved in wound healing. However, SP level reduces in dermis in diabetics and, hence, it was hypothesized that exogenously applied SP could be helpful in improving wound healing in diabetic rats. Excision skin wound was created on the back of diabetic rats and rats were divided into three groups i.e. (i) saline-, (ii) gel- and (iii) SP-treated. Normal saline, pluronic gel and SP (10(-6)M) in gel were topically applied once daily for 19days. SP treatment significantly increased the wound closure, levels of interleukin-10, and expressions of vascular endothelial growth factor, transforming growth factor-beta1, heme oxygenase-1 and endothelial nitric oxide synthase, whereas it significantly decreased the expression of tumor necrosis factor-alpha, interleukin-1beta and matrix metalloproteinases-9 in the granulation/healing tissue. The inflammatory cells were present for long time in normal saline-treated group. Histological evaluation revealed better extracellular matrix formation with marked fibroblast proliferation and collagen deposition in SP-treated group. Early epithelial layer formation, increased microvessel density and greater growth associated protein-43 positive nerve fibers were also evidenced in SP-treated group. In conclusion, SP treatment markedly accelerated cutaneous wound healing in diabetic rats.
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243 122, U.P., India. Electronic address: drvinaykant2001@yahoo.co.in.
Vinay
V
Kant
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243 122, U.P., India.
Dinesh
D
Kumar
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243 122, U.P., India.
Dhirendra
D
Kumar
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243 122, U.P., India.
Raju
R
Prasad
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243 122, U.P., India.
Anu
A
Gopal
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243 122, U.P., India.
Nitya N
NN
Pathak
Division of Pathology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243 122, U.P., India.
Pawan
P
Kumar
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243 122, U.P., India.
Surender K
SK
Tandan
D000287:Administration, Topical; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003094:Collagen / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics / Q000473:pathology*; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D013311:Streptozocin; D013373:Substance P / Q000008:administration & dosage* / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D001786:Blood Glucose; D019922:GAP-43 Protein; D053583:Interleukin-1beta; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D013373:Substance P; D013311:Streptozocin; D003094:Collagen; D052250:Nitric Oxide Synthase Type III; D051547:Heme Oxygenase-1; D020780:Matrix Metalloproteinase 9
Diabetic rats; Epithelial layer; Microvessel density; Substance P; Wound healing