PMID- 26679676
OWN - NLM
STAT- MEDLINE
DCOM- 20160930
LR  - 20220408
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 30
DP  - 2016 Jan
TI  - Bilirubin modulated cytokines, growth factors and angiogenesis to improve 
      cutaneous wound healing process in diabetic rats.
PG  - 137-149
LID - S1567-5769(15)30205-8 [pii]
LID - 10.1016/j.intimp.2015.11.037 [doi]
AB  - Bilirubin has shown cutaneous wound healing potential in some preliminary 
      studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic 
      rats by modulating important healing factors/candidates and antioxidant 
      parameters in a time-dependent manner. Diabetes was induced in male Wistar rats 
      by streptozotocin. In all diabetic rats wounds were created under pentobarbitone 
      anesthesia. All the rats were divided into two groups, of which one (control) was 
      treated with ointment base and other with bilirubin ointment (0.3%). Wound closer 
      measurement and tissue collection were done on days 3, 7, 14 and 19 
      post-wounding. The relative expressions of hypoxia inducible factor-1 alpha 
      (HIF-1alpha), vascular endothelial growth factor (VEGF), stromal cell-derived 
      factor-1 alpha (SDF-1alpha), transforming growth factor- beta1 (TGF-beta1()), tumor 
      necrosis factor-alpha (TNF-alpha) and interlukin-10 (IL-10) mRNA and proteins and the 
      mRNA of interlukin-1 beta (IL-1beta) and matrix metalloprteinase-9 (MMP-9) were 
      determined in the wound tissues. CD-31 staining and collagen content were 
      evaluated by immunohistochemistry and picrosirius red staining, respectively. 
      Histopathological changes were assessed by H&E staining. The per cent wound 
      closer was significantly higher from day 7 onwards in bilirubin-treated rats. 
      HIF-1alpha, VEGF, SDF-1alpha, TGF-beta1, IL-10 mRNA and protein levels were significantly 
      higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and 
      protein level of TNF-alpha and the mRNA of IL-1beta and MMP-9 were progressively and 
      markedly reduced in bilirubin-treated rats. The collagen deposition and formation 
      of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly 
      facilitated cutaneous wound healing in diabetic rats by modulating growth 
      factors, cytokines, neovasculogenesis and collagen contents to the wound site. 
      Topical application of bilirubin ointment might be of great use in cutaneous 
      wound healing in diabetic patients.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Ram, Mahendra
AU  - Ram M
AD  - Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, 
      Izatnagar 243 122 (U.P.), India.
FAU - Singh, Vishakha
AU  - Singh V
AD  - Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, 
      Izatnagar 243 122 (U.P.), India.
FAU - Kumawat, Sanjay
AU  - Kumawat S
AD  - Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, 
      Izatnagar 243 122 (U.P.), India.
FAU - Kant, Vinay
AU  - Kant V
AD  - Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, 
      Izatnagar 243 122 (U.P.), India.
FAU - Tandan, Surendra Kumar
AU  - Tandan SK
AD  - Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, 
      Izatnagar 243 122 (U.P.), India.
FAU - Kumar, Dinesh
AU  - Kumar D
AD  - Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, 
      Izatnagar 243 122 (U.P.), India. Electronic address: dineshks17@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20151208
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Cytokines)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Ointments)
RN  - 9007-34-5 (Collagen)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Animals
MH  - Bilirubin/*administration & dosage
MH  - Collagen/metabolism
MH  - Cytokines/genetics/metabolism
MH  - Diabetes Mellitus, Experimental/complications/*drug therapy
MH  - Gene Expression Regulation/drug effects
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Intercellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Male
MH  - Neovascularization, Pathologic/etiology/*prevention & control
MH  - Ointments/*administration & dosage
MH  - Rats
MH  - Rats, Wistar
MH  - Skin/*drug effects/metabolism/pathology
MH  - Wound Healing/drug effects
OTO - NOTNLM
OT  - Angiogenesis
OT  - Bilirubin
OT  - Cytokines
OT  - Diabetic rats
OT  - Growth factors
OT  - Wound healing
EDAT- 2015/12/19 06:00
MHDA- 2016/10/01 06:00
CRDT- 2015/12/19 06:00
PHST- 2015/05/25 00:00 [received]
PHST- 2015/11/29 00:00 [revised]
PHST- 2015/11/30 00:00 [accepted]
PHST- 2015/12/19 06:00 [entrez]
PHST- 2015/12/19 06:00 [pubmed]
PHST- 2016/10/01 06:00 [medline]
AID - S1567-5769(15)30205-8 [pii]
AID - 10.1016/j.intimp.2015.11.037 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2016 Jan;30:137-149. doi: 10.1016/j.intimp.2015.11.037. Epub 
      2015 Dec 8.