Helmi, Nur Farihin Mohamad Helmi
(2023)
Understanding the synergistic action of serum inflammatory markers and growth factors profile in excisional wound healing phases in rats’experimental model intraperitoneally treated with echinodermata glycosaminoglycans (GAGS).
Masters thesis, Universiti Sains Malaysia.
Abstract
Stichopus vastus; sea cucumbers, is a marine invertebrate which is rich in
glycosaminoglycans (GAGs). This sea cucumber has long been utilised as traditional
therapy alternatives, especially as wound healing remedy. The current study is
designed in order to explore the effect of GAGs from integument wall of S. vastus
species for wound healing properties in rats by intra-peritoneal injection with GAGs
extract daily. Twenty-four (24) male Sprague Dawley rats were divided into four
groups (n=6) which are control group; given phosphate buffer saline (PBS) and three
treated groups of GAGs; at 2mg/kg, 4mg/kg and 6mg/kg body weight, respectively.
Rats weight from 250-400 grams were treated with GAGs daily for 12 days. Skin graft
and blood samples were taken for macroscopic and microscopic evaluation; while
protein and gene expression of selected biomarkers (IL6, IL10, MMP-9, TNF-α, TGF-
β1, VEGF-A, PDGF-A) were analysed with ELISA and qRT-PCR, respectively. In the
macroscopic study, there was no significant difference (p>0.008) noted between all
groups. Meanwhile, in the microscopic study, there were also no noted significant
difference (p>0.008) between the groups in epithelialization, inflammation, fibroblast
proliferation, collagen fibers organization and new vessels formation. However, via
this research activities, it was revealed that, both either 2mg/kg or 4mg/kg of extracted
glycosaminoglycans (GAGs) from S. vastus can enhance wound healing process at
early phase of the wound healing when investigated macro and microscopically. In addition, in protein expression, the study disclosed that, there were significant
difference (p<0.05) between treatment and control groups in IL-6, IL-10, MMP-9,
VEGF-A and TNF-α while, there were no significant difference in PDGF-A and TGF-
β1. On the other hand, gene expression study showed that, there were no significant
difference (p>0.05) in all selected biomarkers. All in all, protein expression and gene
expression revealed that, 2mg/kg of GAGs effects biomarkers: IL-6, IL-10, MMP-9
and VEGF-A, while 4mg/kg of GAGs effects biomarkers: TNF-α, PDGF-A and TGF-
β1. GAGs extraction concentration selectively effects these biomarkers, as the wound
healing cascade itself in a complex process. Extracted glycosaminoglycans (GAGs)
from S. vastus have the potential to act as promoter for pro-inflammatory, antiinflammatory,
anti-microbial effect on wound healing by targeting cytokines,
chemokines and enzyme that participate in wound healing cascade to execute their
pathophysiological roles. In this study the GAGs extraction concentration was
observed to have selectively effects the biomarkers activities, however, as the wound
healing cascade itself is actually a complex process, the pathway of this mechanism
which consist of interactions of cytokines, chemokines and enzyme must be carefully
investigated for further detail study.
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