Healing enhancement of diabetic wounds by locally infiltrated epidermal growth factor is associated with systemic oxidative stress reduction

Ojalvo, Ariana G.; Acosta, Jorge Berlanga; Mendoza‐Marí, Yssel; Fernández‐Mayola, Maday; Pérez, Calixto Valdés; Gutiérrez, William Savigne; Marichal, Ileydis Iglesias; Seijas, Eduardo Álvarez; Kautzman, Alicia Molina; Pacheco, Angélica Estrada; Armstrong, David G.

doi:10.1111/iwj.12592

Cited by 42 publications

(45 citation statements)

References 60 publications

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“…Diabetes is a multifactorial toxic entity in which glucotoxicity is associated with increased reactive oxygen species levels, disruption of the balance between pro‐degradative an pro‐synthetic forces, as to the AGE/RAGE noxious impact, thus leading to cellular proliferative and survival reserves demise . In line with this, our group had previously demonstrated that ulcerated diabetic subjects behave as a particular diseased group, as they exhibit an exacerbation of the oxidative stress arm as compared with non‐ulcerated diabetics . Here, we confirm that nine EGF infiltrations over 3 weeks were sufficient to reduce the circulating levels of oxidative reactants although with no effect on the circulating antioxidant defence reserves.…”

Section: Discussionsupporting

confidence: 86%

“…The present study validates previous observations of our group, demonstrating the systemic impact of locally infiltrated EGF in reestablishing a pro‐physiological redox balance. Furthermore, here we show that EGF pharmacodynamic bounties also encompass the attenuation of endovascular pro‐inflammatory markers with dramatic negative impact in diabetic individuals' general homeostasis.…”

Section: Introductionsupporting

confidence: 92%

“…Our group had previously demonstrated that EGF intralesional infiltrations for 3–4 weeks (9–12 infiltrations) associated with the standard of care, beyond promoting granulation tissue over 75% of the wounded area, and contributed to restore the circulating levels of several redox biology parameters up to values close to those of non‐ulcerated diabetic patients and non‐diabetic subjects . In this opportunity, using a similar clinical investigation protocol and under a 3‐week treatment timeframe, we investigated the impact of EGF intervention on four major fields including: ordinary/routine blood chemistry, acute reactants and pro‐inflammatory mediators, oxidative and nitrosilation stress, and the AGE/RAGE axis.…”

Section: Discussionmentioning

confidence: 99%

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Systemic translation of locally infiltrated epidermal growth factor in diabetic lower extremity wounds

García‐Ojalvo

Acosta

Figueroa-Martínez³

et al. 2019

International Wound Journal

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Diabetic foot ulcer is one of the most frightened diabetic complications leading to amputation disability and early mortality. Diabetic wounds exhibit a complex networking of inflammatory cytokines, local proteases, and reactive oxygen and nitrogen species as a pathogenic polymicrobial biofilm, overall contributing to wound chronification and host homeostasis imbalance. Intralesional infiltration of epidermal growth factor (EGF) has emerged as a therapeutic alternative to diabetic wound healing, reaching responsive cells while avoiding the deleterious effect of proteases and the biofilm on the wound's surface. The present study shows that intralesional therapy with EGF is associated with the systemic attenuation of pro‐inflammatory markers along with redox balance recovery. A total of 11 diabetic patients with neuropathic foot ulcers were studied before and 3 weeks after starting EGF treatment. Evaluations comprised plasma levels of pro‐inflammatory, redox balance, and glycation markers. Pro‐inflammatory markers such as erythrosedimentation rate, C‐reactive protein, interleukin‐6, soluble FAS, and macrophage inflammatory protein 1‐alpha were significantly reduced by EGF therapy. Oxidative capacity, nitrite/nitrate ratio, and pentosidine were also reduced, while soluble receptor for advanced glycation end‐products significantly increased. Overall, our results indicate that the local intralesional infiltration of EGF translates in systemic anti‐inflammatory and antioxidant effects, as in attenuation of the glycation products' negative effects.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Systemic translation of locally infiltrated epidermal growth factor in diabetic lower extremity wounds

García‐Ojalvo

Acosta

Figueroa-Martínez³

et al. 2019

International Wound Journal

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“…A number of studies have shown that (11–13) VSD treatment can effectively shorten wound healing time, reduce the pain associated with wound dressing changes, and effectively avoid cross infection. VSD is performed in a closed system, and the negative pressure drainage system promptly removes any exudates and necrotic tissue to achieve zero necrotic tissue accumulation.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of combined treatment with vacuum sealing drainage and recombinant human epidermal growth factor for refractory wounds in the extremities and its effect on serum levels of IL-6, TNF-α and IL-2

2017

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The objective of this study was to investigate the efficacy of combined treatment with vacuum sealing drainage (VSD) and recombinant human epidermal growth factor (rhEGF) for refractory wounds in the extremities, and its effect on serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-2. Ninety-eight patients with refractory wounds in the extremities were recruited and randomly divided into the combined treatment group (underwent VSD and rhEGF treatment) and control group (underwent VSD only) with 49 cases each. Formation of granulation tissue on the wound surface was assessed and scored. The wound healing rate was calculated after 1 week of treatment, and the time of complete healing was recorded. Serum levels of IL-6, IL-2, and TNF-α were measured using enzyme-linked immunosorbent assay. After 1 week of treatment, granulation tissue formation on wound surfaces was significantly improved (p<0.05) compared with that before treatment in both groups. Moreover, granulation tissue formation on wound surfaces was superior in the combined treatment group than in the control group (p<0.05). The wound healing rate was 63.50±4.75% in the combined treatment group and 31.79±3.52% in the control group, and the difference was statistically significant (p<0.05). The time of complete healing was 15.11±2.24 days in the combined treatment group and 19.63±2.76 days in the control group, and the difference was statistically significant (p<0.05). The serum levels of IL-6, IL-2, and TNF-α, in the two groups were significantly lower than those before treatment (p<0.05). Moreover, the levels in the combined treatment group were significantly lower than those in the control group (p<0.05). In conclusion, combined treatment with VSD and rhEGF reduced inflammation and shortened the time of complete healing of refractory wounds in the extremities. Measurement of the levels of related inflammatory factors provided a reference for the prognosis of refractory wounds.

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“…Intra-lesional infiltration of epidermal growth factor (EGF) has emerged as a potential therapeutic alternative to allow for physiological benefit while avoiding the proteolytic environment at the centre of the wound. Intra-lesional administration of EGF was associated with a significant recovery of oxidative stress and antioxidant reserve markers leading the authors to conclude that epidermal growth factor intra-ulcer therapy contributes to restore systemic redox balance in patients with DFUs (96). Furthermore, intralesional insulin injection in DFU showed promising results in terms of wound healing (97).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Genetic and molecular basis of diabetic foot ulcers: Clinical review

Jhamb

Vangaveti

Malabu

2016

Journal of Tissue Viability

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Healing enhancement of diabetic wounds by locally infiltrated epidermal growth factor is associated with systemic oxidative stress reduction

Cited by 42 publications

References 60 publications

Systemic translation of locally infiltrated epidermal growth factor in diabetic lower extremity wounds

Systemic translation of locally infiltrated epidermal growth factor in diabetic lower extremity wounds

Efficacy of combined treatment with vacuum sealing drainage and recombinant human epidermal growth factor for refractory wounds in the extremities and its effect on serum levels of IL-6, TNF-α and IL-2

Genetic and molecular basis of diabetic foot ulcers: Clinical review

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