Deferoxamine modulates cytokines and growth factors to accelerate cutaneous wound healing in diabetic rats

Ram, Mahendra; Singh, Vishal; Kumawat, Sanjay; Kumar, Dhirendra; Lingaraju, Madhu Cholenahalli; Singh, Thakur Uttam; Rahal, Anu; Tandan, Surendra K.; Kumar, Dinesh

doi:10.1016/j.ejphar.2015.06.029

Cited by 60 publications

(47 citation statements)

References 46 publications

(53 reference statements)

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“…Adult male sprague dawley (SD) rats weighing 250-300 g were used in this study. Experimental diabetes mellitus was induced by a single intraperitoneal injection of STZ (Sigma, St. Louis, MO, USA; 60 mg/ kg) 18. Blood glucose levels were monitored after 72 hours and those rats showing blood glucose level above 300 mg/dl were selected for further study.…”

Section: Methodsmentioning

confidence: 99%

Exosomes Derived from Human Endothelial Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogenesis Through Erk1/2 Signaling

Zhang¹,

Chen²,

Hu³

et al. 2016

Int. J. Biol. Sci.

204

183

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Chronic skin wounds represent one of the most common and disabling complications of diabetes. Endothelial progenitor cells (EPCs) are precursors of endothelial cells and can enhance diabetic wound repair by facilitating neovascularization. Recent studies indicate that the transplanted cells exert therapeutic effects primarily via a paracrine mechanism and exosomes are an important paracrine factor that can be directly used as therapeutic agents for regenerative medicine. However, application of exosomes in diabetic wound repair has been rarely reported. In this study, we demonstrated that the exosomes derived from human umbilical cord blood-derived EPCs (EPC-Exos) possessed robust pro-angiogenic and wound healing effects in streptozotocin-induced diabetic rats. By using a series of in vitro functional assays, we found that EPC-Exos could be incorporated into endothelial cells and significantly enhance endothelial cells' proliferation, migration, and angiogenic tubule formation. Moreover, microarray analyses indicated that exosomes treatment markedly altered the expression of a class of genes involved in Erk1/2 signaling pathway. It was further confirmed with functional study that this signaling process was the critical mediator during the exosomes-induced angiogenic responses of endothelial cells. Therefore, EPC-Exos are able to stimulate angiogenic activities of endothelial cells by activating Erk1/2 signaling, which finally facilitates cutaneous wound repair and regeneration.

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Section: Methodsmentioning

confidence: 99%

Exosomes Derived from Human Endothelial Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogenesis Through Erk1/2 Signaling

Zhang¹,

Chen²,

Hu³

et al. 2016

Int. J. Biol. Sci.

204

183

View full text Add to dashboard Cite

show abstract

“…The remodeling stage is the most important phase as it determines the strength and manifestation of the healed tissue. Wound healing is a complex series of interrelated events that are mediated through these phases by a wide range of chemically coordinated cellular processes as well as hormonal influences1. Wound healing commences at the time an injury occurs and progresses for varying lengths of time based on the extent of the injury.…”

mentioning

confidence: 99%

In vivo Assessment of Antioxidant and Wound Healing Improvement of a New Schiff Base Derived Co (II) Complex in Rats

El-Ferjani

Ahmad

Dhiyaaldeen

et al. 2016

Sci Rep

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Co (II) complex (CMLA) was investigated to evaluate the rate of wound healing in rats. Animals were placed into four groups: gum acacia, Intrasite gel, 10 and 20 mg/ml of CMLA. Wounds were made on the dorsal neck area, then treated with Intrasite gel or CMLA; both of these treatments led to faster healing than with gum acacia. Histology of the wounds dressed with CMLA or Intrasite gel displayed a smaller scar width, required less time to heal and showed more collagen staining and fewer inflammatory cells in comparison to wounds dressed with the vehicle. Immunohistochemistry for Hsp70 and TGF-β showed greater staining intensity in the treated groups compared to the vehicle group. Bax staining was less intense in treated groups compared to the vehicle group, suggesting that CMLA and Intrasite gel provoked apoptosis, responsible for the development of granulation tissue into a scar. CD31 protein analysis showed that the treated groups enhanced angiogenesis and increased vascularization compared to the control group. Furthermore, a significant increase in the levels of GPx and SOD and a decrease in MDA were also observed in the treated groups. This results suggest that CMLA is a potentially promising agent for the wounds treatment.

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“…Pigs treated with DFO showed a pronounced attenuation of IL-6 production, a cytokine that plays a major role in inflammatory processes (Vlahakos et al, 2012). Topically application of DFO on cutaneous wounds in diabetic rats induced faster healing and elevated significantly the levels of TGF-β1 and IL-10, whereas those of TNFα and IL-1β were markedly reduced (Ram et al, 2015). In our experimental setup, the reduced IFNγ, IL-2 and IL-10 secretion by DFO stimulated PBMC was reversed after addition of iron, whereas the decrease in IL-1β and IL1ra was not affected by iron supplementation.…”

Section: Discussionmentioning

confidence: 99%

Does Iron Modulate Cytokine Production by Desferrioxamine Treated Mononuclear Cells?

Bessler

Djaldetti

2018

OnLine Journal of Biological Sciences

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Iron is an essential element for maintaining the normal function of cellular and multicellular organisms and it is closely associated with inflammation and immunity. Macrophages and lymphocytes play an important role in its homeostasis. Hereby we have evaluated cytokine production by iron depleted and iron supplemented human peripheral blood mononuclear cells (PBMC) from healthy adult donors. Non-stimulated or stimulated PBMC (lipopolysaccharide-LPS or phorbol-myristate acetate-PMA and ionomycin) were incubated for 24 h without or with desferrioxamine (DFO) and the quantity of TNFα, IL-1β, IL-6, IFNγ, IL-2, IL-10 and IL-1ra in the supernatants was evaluated using ELISA kits. In addition, cytokine levels were determined in supernatants of cultures to which DFO was added for 2 h followed by 24 h of incubation with iron. The secretion of IL-1β, IL-6 and IL-1ra by non-stimulated PBMC and that of IL-1β by LPS-stimulated cells was dose-dependently enhanced following incubation with increasing concentrations of DFO between 25 and 100 µM. On the other hand LPS-induced production of IL-10 and PMA/ionomycin stimulated IL-2 and IFNγ secretion was dose dependently reduced. The inhibited IFNγ, IL-2 and IL-10 secretion by stimulated PBMC caused by DFO was reversed after incubation with iron at concentrations similar to those in human serum. However, the inhibition of LPS-induced IL-1ra or IL-1β production induced by DFO was not affected by iron supplementation. The results of the study underline the importance of intra and/or extracellular iron concentration and DFO for the release of inflammatory cytokines by human peripheral blood mononuclear cells.

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Deferoxamine modulates cytokines and growth factors to accelerate cutaneous wound healing in diabetic rats

Cited by 60 publications

References 46 publications

Exosomes Derived from Human Endothelial Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogenesis Through Erk1/2 Signaling

Exosomes Derived from Human Endothelial Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogenesis Through Erk1/2 Signaling

In vivo Assessment of Antioxidant and Wound Healing Improvement of a New Schiff Base Derived Co (II) Complex in Rats

Does Iron Modulate Cytokine Production by Desferrioxamine Treated Mononuclear Cells?

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