Oral administration of antioxidants improves skin wound healing in diabetic mice

Type 1 diabetes is associated with systemic low grade inflammation (LGI). We have previously shown that LGI in diabetic mice depends on systemic circulation of leukotriene (LTB4) which potentiates the toll-like/IL1β receptors response in macrophages. Impaired wound healing is an important co-morbidity in diabetes, and macrophages play a key role in this process. Here, we investigated the role of leukotrienes on monocytes and macrophages phenotype and in the impaired wound healing in diabetic mice. Type 1 diabetes was induced with streptozotocin in 129SvE wild-type (WT) and leukotrienes-deficient 5LO−/− (5-lipoxygenase knockout) mice. In diabetics, the systemic levels of LTB4, TNF-α, IL-6, IL-10, IL-12 and IFNγ were increased as well as the frequency of pro-inflammatory monocytes (CD11b+Ly6ChighLy6G−) compared to healthy mice. In diabetic 5LO−/− mice, these parameters were similar to those in healthy mice. Resident peritoneal macrophages from diabetic WT mice showed a classically activated M1-like phenotype (high Nos2, Stat and Il12 expression, and nitrite levels). Macrophages from diabetic 5LO−/− mice presented alternatively activated M2-macrophages markers (high Arg1 and Chi3l3 expression and arginase activity) and when stimulated with IL4, enhanced phosphorylated-STAT6. Cutaneous wound healing in diabetic WT mice was impaired, which correlated with the decreased frequency of M2-macrophages (CD45+F4/80+CD206+) in the lesions. In diabetic 5LO−/− mice, the frequency of M2-macrophages in the wound was similar to that in healthy mice, suggesting that the impaired healing of diabetic mice depends on 5LO products. The inhibition of leukotrienes or antagonism of its receptors could be a therapeutic alternative for diabetic patients with impaired healing.

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“…S3 ). About 10,000 events were analyzed 41 . In the full gate strategy, doublets, debris and dead cells were gated out.…”

Section: Methodsmentioning

confidence: 99%

Impaired wound healing in type 1 diabetes is dependent on 5-lipoxygenase products

Ramalho

Filgueiras

Silva-Jr

et al. 2018

Sci Rep

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“…This wound-healing effect of the flowers and leaves of A. majus is related to their antioxidant activity. The interrelation of antioxidant activity and wound-healing effect was studied recently by Reference [52] on diabetic mice. The study findings denoted that diabetes leads to depleted levels of proinflammatory cytokines that result in delayed inflammatory cascade, and thus a slower healing process.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Evaluation of Antirrhinum majus’ Wound-Healing Activity

2018

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Mediterranean-native perennial plant Antirrhinum majus was scrutinized in this study for its antioxidant activity and its total phenolic content in order to test for the plant’s wound-healing capability. The traditional uses of this plant to treat gum scurvy, various tumors, ulcers, and hemorrhoids were the main idea behind this study. Leaves and flowers of the A. majus were extracted by maceration. Pilot qualitative phytochemical tests were made to check the presence of various secondary metabolites. Quantitatively, the flowers’ macerate indicated superlative results regarding antioxidant activity and total phenolic content. However, the in vivo wound-healing capability study was made using 30 Wistar strain albino rats. This innovative part of the study revealed that the healing power of the flowers’ extract ointment (5% w/w) was superior compared to the leaves’ extract (5% w/w) and the positive-control ointments (MEBO) (1.5% w/w) (p ≤ 0.001). This activity was assessed by visual examination, wound-length measurement, and estimation of hydroxyproline content. Antirrhinum majus is a promising plant to be considered for wound healing. However, further testing (including histological examination and high-performance liquid chromatography (HPLC) analysis) is necessary to understand more about its mechanisms of action.

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“…The membranes, previously hydrated with 0.9% saline, were placed under the lesion area and sutured at two points on opposite sides with 7-0 Nylon thread. To control pain, tramadol hydrochloride IP (20 mg/kg) was used immediately after the surgical procedure and in the three days following the surgery [34][35][36].…”

Section: Surgical Proceduresmentioning

confidence: 99%

Effects of Electrospun Fibrous Membranes of PolyCaprolactone and Chitosan/Poly(Ethylene Oxide) on Mouse Acute Skin Lesions

et al. 2020

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Polycaprolactone (PCL) is a synthetic polymer with good mechanical properties that are useful to produce biomaterials of clinical application. It can be successfully combined with chitosan, which enhances the biomaterial properties through the modulation of molecular and cellular mechanisms. The objective of this study was to evaluate the effects of the use of electrospun fibrous membranes consisting of polycaprolactone (PCL) or polycaprolactone coated with chitosan and poly(ethylene oxide) (PCL+CHI/PEO) on mouse skin lesions. Sixty four Black-57 mice were divided into PCL and PCL+CHI/PEO groups. A 1 cm2 lesion was made on the animals’ backs, and the membranes were sutured in place. The tissues were extracted on the 3rd, 7th, and 14th days after the lesion. The tissues were analyzed by histology with Hematoxylin and Eosin (H&E) and Sirius Red stains, morphometry, immunohistochemistry, and Western blot. On the 3rd, 6th, and 9th days after the lesion, the PCL+CHI/PEO group showed a higher wound-healing rate (WHR). On the 3 day, the PCL+CHI/PEO group showed a greater amount of inflammatory infiltrate, greater expression of proliferating cell nuclear antigen (PCNA), and smooth muscle actin (α-SMA) (p < 0.05) compared to the PCL group. On the 7th day after the lesion, the PCL+CHI/PEO group showed a greater amount of inflammatory infiltrate, expression of Tumor Necrosis Factor (TNF-α) and PCNA (p < 0.05). In addition, it showed a greater immunolabeling of Monocyte Chemoattractant Protein-1 (MCP-1) and deposition of collagen fibers compared to the PCL group. The PCL+CHI/PEO membrane modulated the increase in the inflammatory infiltrate, the expression of MCP-1, PCNA, and α-SMA in lesions of mice.

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Oral administration of antioxidants improves skin wound healing in diabetic mice

Cited by 27 publications

References 36 publications

Impaired wound healing in type 1 diabetes is dependent on 5-lipoxygenase products

Impaired wound healing in type 1 diabetes is dependent on 5-lipoxygenase products

In Vivo Evaluation of Antirrhinum majus’ Wound-Healing Activity

Effects of Electrospun Fibrous Membranes of PolyCaprolactone and Chitosan/Poly(Ethylene Oxide) on Mouse Acute Skin Lesions

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