A Study on the Effects of Modulation of Intracellular Calcium on Excisional Wound Healing in Rabbit (original) (raw)

The Role of Calcium in Wound Healing

International Journal of Molecular Sciences

Skin injury is quite common, and the wound healing is a complex process involving many types of cells, the extracellular matrix, and soluble mediators. Cell differentiation, migration, and proliferation are essential in restoring the integrity of the injured tissue. Despite the advances in science and technology, we have yet to find the ideal dressing that can support the healing of cutaneous wounds effectively, particularly for difficult-to-heal chronic wounds such as diabetic foot ulcers, bed sores, and venous ulcers. Hence, there is a need to identify and incorporate new ideas and methods to design a more effective dressing that not only can expedite wound healing but also can reduce scarring. Calcium has been identified to influence the wound healing process. This review explores the functions and roles of calcium in skin regeneration and reconstruction during would healing. Furthermore, this review also investigates the possibility of incorporating calcium into scaffolds and ex...

Calcium: a potential central regulator in wound healing in the skin

Wound Repair and Regeneration, 2002

Calcium has an established role in the normal homeostasis of mammalian skin and serves as a modulator in keratinocyte proliferation and differentiation. Gradients of calcium concentration increasing from 0.5 mM in the basal layer to > 1.4 mM in the stratum granulosum are consistent with migration patterns in response to minor abrasion (normal wear). Dermal fibroblasts require calcium but are approximately 100 times less sensitive than keratinocytes. Normal calcium metabolism in the skin is dependent on cell membrane and cytosolic calcium binding proteins (calmodulin, cadherins, etc.), but their modulation through parathyroid hormone, vitamin D or growth factors in normal or damaged tissue is not well documented. In wound repair, calcium is predominantly involved as Factor IV in the hemostatic phase, but it is expected to be required in epidermal cell migration and regeneration patterns in later stages of healing. Calcium alginate dressings are designed to liberate calcium early in the acute phase to promote hemostasis, but it is presently unclear whether the supplementary calcium influences the intracellular environment at later stages of wound repair, notably during the remodeling phase. Although experimental studies suggest that control of calcium is obligatory in wound management, we know very little as to how calcium in the wound bed is modulated through hormones, vitamin D, or various growth factors. Also, there is limited information as to how calcium released either from dressings, platelets, or from the circulation through the action of parathyroid hormone, growth factors or other modulators influences cell migration and remodeling in skin wounds, although experimental models suggest that management of calcium is essential in wound management. (WOUND REP REG 2002;10: 271-285) Calcium is a divalent metal cation and the most abundant metal in the mammalian body. It exists in a variety of forms, with as much as 99% of body calcium located in the mineralized tissues of bones and teeth and the remainder distributed widely among soft tissues. Over the past 50 years, research efforts on calcium metabolism have focused on its mobilization to and release from bone, control of calcemia, and the dietary uptake and requirements for calcium at different ages and under different physiological and pathological circumstances. 1-3 The development of new antibody technology, fluorescent probes, analytical chemistry and molecular biology techniques in recent years has led to many significant advances in understanding the importance of extra-and intracellular calcium in such diverse physiological functions as muscular contraction, cardiovascular function, neurological activity, and the role of defects in calcium metabolism as

Verapamil, a Calcium-Channel Blocker, Improves the Wound Healing Process in Rats with Excisional Full-Thickness Skin Wounds Based on Stereological Parameters

Advances in Skin & Wound Care, 2016

BACKGROUND Previous studies indicated that both Plantago major and Aloe vera have anti-inflammatory, tissue regeneration, antioxidant, and immune-stimulatory effects. It is assumed that a mixture of these two herbal medicines may provide a potent material in treatment of skin wound injuries. Therefore, in this study we investigated the effects of Plantago major and Aloe vera mixture in the process of wound healing in rat models according to stereological parameters. METHODS In an experiential study, 36 male Sprague-Dawley rats (200±20 g) were randomly assigned into three groups (n=12): The control group which received no treatment, gel base treated group, and the 5% Plantago major and 5% Aloe vera mixture gel treated group (PA group). Treatments were done every 24 hrs for 15 days. Wound closure rate, volume densities of the collagen bundles and the vessels, vessel's length density and mean diameter, and fibroblast populations were estimated using stereological methods. RESULTS PA treated group showed faster wound closure rate in comparison with control and gel-base groups (p<0.05). Numerical density of fibroblasts, volume density of collagen bundles, mean diameter, and volume densities of the vessels in PA group were significantly higher than the control and the gel-base treated groups (p<0.05). CONCLUSION We showed that Plantago major and Aloe vera mixture has the ability to improve wound healing by enhancing fibroblast proliferation, collagen bundle synthesis and re-vascularization in skin injuries.

Wound Healing Parameters at Different Time Intervals in Excision Wounds of Rabbit

Journal of Veterinary Advances, 2014

Wound healing is a fundamental response to tissue injury and several integrated cellular and biochemical events are set in motion immediately after injury leading to re-establishment of structural and functional integrity with regains of strength of injured tissue. present study was under taken to study the accumulation of different biochemical molecules at the wound site at specific time intervals. 36 clinically healthy rabbits in the age group of 3-9 months were used as experimental animals. Wound contraction was recorded on day 2, 4, 6, 8, 10, 12 and 14 after creation of wound. Biochemical parameters hydroxyproline, glucosamine, protein and DNA was estimated at I hour, 3 hour, 6 hour, 24 hours, 5 days, 8 days, 11 and 14 post wounding days. There was a decrease in the wound area from day 2 and this trend continued up to the last observation of the study. On day 14 there was 100% contraction of the wound area. There was also an increase in the accumulation of hydroxyproline and glu...

Pharmacological treatment of wounds

Seminars in Cutaneous Medicine and Surgery, 1998

Systemic treatment of patients with wounds can be directed at several physiological aspects of healing during the consecutive phases of tissue repair. Many approaches to pharmacological treatment have been tested in vitro, in animal experiments, or in clinical studies. Investigators and clinicians focus on treating underlying metabolic, infectious, inflammatory, or hemorrheological diseases and their complications. Drug treatment is often adjuvant or complementary to other measures such as compression, surgical intervention, reconstruction, or reopening procedures. This compounding fact can render interpretation of the results more difficult. As systemic treatment is not always without side-effects; local wound management is an option to consider. Topically applied growth factors certainly have the potential to influence the healing process. An indirect way of providing growth factors to wounds and chronic ulcers can be achieved by the application of grafts, cultured keratinocytes, and skin substitutes. Modulation of angiogenesis during wound healing is a recent target for research and treatment. Future reviews probably also will include genetic engineering methods for influencing wound healing.

Topically applied substance P enhanced healing of open excision wound in rats

European Journal of Pharmacology, 2013

Significant social and financial burden due to wounds need newer drugs/formulations to speed up the healing process. Substance P (SP), a neuropeptide, is associated with release of various cytokines and growth factors from inflammatory, epithelial and endothelial cells. In the present study, temporal effects of topically applied SP (10 −7 M in normal saline) were evaluated in the modulation of various cytokines and growth factors that participate in cutaneous wound healing. Gross examination of full thickness open excision wound in rats revealed that once daily topical application of SP significantly increased the wound closure, as compared to control group. SP treatment significantly increased tumor necrosis factorα (TNF-α) and decreased interleukin 10 (IL-10) levels on day 3. On the contrary, on day 7 level of TNF-α decreased and that of IL-10 increased. The mRNA and protein expressions of vascular endothelial growth factor (VEGF) and transforming growth factor-β 1 (TGF-β 1) increased on days 3 and 7, and decreased on day 14 in SP-treated wounds. Histopathological evaluation of hematoxylin and eosin stained wound sections showed that SP treatment produced increased early leukocytes infiltration, fibroblast proliferation, angiogenesis, collagen deposition and re-epithelialization. Results of the present study demonstrate that topical application of SP enhanced wound healing by modulating cytokines, growth factors and cells. Based on the results, it is suggested that SP could be of beneficial use in diabetic wounds where levels of VEGF, TGF-β 1 and SP decrease along with impairment of inflammatory reaction.

Early and late calcium waves during wound healing in corneal endothelial cells

Wound Repair and Regeneration, 2012

Immediately after wounding, bovine corneal endothelial cells develop a fast calcium wave that propagates from the wound border to the rest of the monolayer and extinguishes in approximately 5 minutes. One hour after wounding, a late, slow calcium wave (SCW) develops concomitantly to the depolarization of the plasma membrane potential of the border cells. The incorporation of inhibitors of the epithelial sodium channel and of the sodium-calcium exchanger produces inhibition of the membrane depolarization and the SCW, and diminishes the rate of wound healing. The L-type calcium channel blocker nimodipine does not have any effect on the SCW. The reversible inhibition of the fast calcium wave does not affect the SCW and only slightly decreases the velocity of healing. Our results suggest that the SCW is at least partially produced by the coupling of the epithelial sodium channel and the sodium-calcium exchanger functioning in reverse mode. They also suggest that the SCW may play a role in the overall healing process.

Effect of Topical Application of Different Substances on Fibroplasia in Cutaneous Surgical Wounds

ISRN Dermatology, 2012

Background. Fibroblasts on the edges of a surgical wound are induced to synthesize collagen during the healing process which is known as fibroplasia.Objective. The aim of this study was to determine the effect of the application of different substances on fibroplasia of cutaneous surgical wounds on rats.Materials and Methods. 48Wistarrats were divided into three groups. A surgical wound 1 cm in diameter and 1 mm in depth was created on the dorsum of each animal. The surgical wounds were submitted to the topical application of an alcoholic extract of 30% propolis, 70% alcohol, or 0.001% dexamethasone in a cream base every 12 hours. The animals were sacrificed three, seven, 14, and 28 days postoperatively. The specimens were histologically processed and stained with Masson’s trichrome. The assessment of fibroplasia was performed using a scoring system: (1) 5 to 25% collagen deposition; (2) 26 to 50% collagen deposition; (3) 51 to 75% collagen deposition; (4) more than 75% collagen de...