scholarly journals Edaravone-Loaded Alginate-Based Nanocomposite Hydrogel Accelerated Chronic Wound Healing in Diabetic Mice

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 285 ◽  
Author(s):  
Ying Fan ◽  
Wen Wu ◽  
Yu Lei ◽  
Caroline Gaucher ◽  
Shuchen Pei ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
High Dose ◽  
Nanocomposite Hydrogel ◽  
Diabetic Mice ◽  
Key Factor ◽  
Dose Dependent

Refractory wound healing is one of the most common complications of diabetes. Excessive production of reactive oxygen species (ROS) can cause chronic inflammation and thus impair cutaneous wound healing. Scavenging these ROS in wound dressing may offer effective treatment for chronic wounds. Here, a nanocomposite hydrogel based on alginate and positively charged Eudragit nanoparticles containing edaravone, an efficient free radical scavenger, was developed for maximal ROS sequestration. Eudragit nanoparticles enhanced edaravone solubility and stability breaking the limitations in application. Furthermore, loading these Eudragit nanoparticles into an alginate hydrogel increased the protection and sustained the release of edaravone. The nanocomposite hydrogel is shown to promote wound healing in a dose-dependent way. A low dose of edaravone-loaded nanocomposite hydrogel accelerated wound healing in diabetic mice. On the contrary, a high dose of edaravone might hamper the healing. Those results indicated the dual role of ROS in chronic wounds. In addition, the discovery of this work pointed out that dose could be the key factor limiting the translational application of antioxidants in wound healing.

scholarly journals Possible Protective Role of Melatonin in Pediatric Infectious Diseases and Neurodevelopmental Pathologies

2020 ◽  
Vol 10 (01) ◽  
pp. e104-e109
Author(s):  
Antonio Molina-Carballo ◽  
Antonio Emilio Jerez-Calero ◽  
Antonio Muñoz-Hoyos
Keyword(s):  
Endothelial Cell ◽  
Free Radical ◽  
Chronic Administration ◽  
Protective Role ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Energetic Metabolism ◽  
Beneficial Effects ◽  
Molecular Crosstalk

AbstractMelatonin, produced in every cell that possesses mitochondria, acts as an endogenous free radical scavenger, and improves energetic metabolism and immune function, by complex molecular crosstalk with other intracellular compounds. There is greatly increasing evidence regarding beneficial effects of acute and chronic administration of high melatonin doses, in infectious, developmental, and degenerative pathologies, as an endothelial cell and every cell protectant.

Metabolism is not a Major Contributor to the Toxicity of Piperaquine, a Major Partner Antimalarial in Artemisinin-Based Combination Therapy

2021 ◽  
Vol 22 ◽  
Author(s):  
Liyuan Zhang ◽  
Zhaohua Liu ◽  
Yunrui Zhang ◽  
Yuewu Xie ◽  
Jie Xing
Keyword(s):  
Histopathological Examination ◽  
High Dose ◽  
Mrna Levels ◽  
Apoptosis Pathway ◽  
Hepatocellular Damage ◽  
Serum Biochemical ◽  
Oral Doses ◽  
Dose Dependent ◽  
Cumulative Exposures

Background: Hepatocellular damage has been reported for the antimalarial piperaquine (PQ) in the clinic after cumulative doses. Objectives: The role of metabolism in PQ toxicity was evaluated, and the mechanism mediating PQ hepatotoxicity was investigated. Method: The toxicity of PQ and its major metabolite (PQ N-oxide; M1) in mice was evaluated in terms of serum biochemical parameters. The role of metabolism in PQ toxicity was investigated in mice pretreated with an inhibitor of CYP450 (ABT) and/or FMO enzyme (MMI). The dose-dependent pharmacokinetics of PQ and M1 were studied in mice. Histopathological examination was performed to reveal the mechanism mediating PQ hepatotoxicity. Results: Serum biochemical levels (ALT and BUN) increased significantly (P < 0.05) in mice after three-day oral doses of PQ (> 200 mg/kg/day), indicating hepatotoxicity and nephrotoxicity of PQ at a high dose. Weaker toxicity was observed for M1. Pretreatment with ABT and/or MMI did not increase PQ toxicity. PQ and M1 showed linear pharmacokinetics in mice after a single oral dose, and multiple oral doses led to their cumulative exposures. Histopathological examination showed that a high dose of PQ (> 200 mg/kg/day for three days) could induce hepatocyte apoptosis. The mRNA levels of targets in NF-κB and p53 pathways could be up-regulated by 2-30-fold in mice by PQ or M1. Conclusions: PQ metabolism led to detoxification of PQ, but there was a low possibility of altered toxicity induced by metabolism inhibition. The hepatotoxicity of PQ and its N-oxidation metabolite was partly mediated by NF-κB inflammatory pathway and p53 apoptosis pathway.

scholarly journals Silk derived formulations for accelerated wound healing in diabetic mice

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10232
Author(s):  
Muniba Tariq ◽  
Hafiz Muhammad Tahir ◽  
Samima Asad Butt ◽  
Shaukat Ali ◽  
Asma Bashir Ahmad ◽  
...  
Keyword(s):  
Wound Healing ◽  
Silk Fibroin ◽  
Chronic Wounds ◽  
Histological Analysis ◽  
Healing Process ◽  
Aloe Vera ◽  
Wound Contraction ◽  
Wound Dressings ◽  
Control Group ◽  
Diabetic Mice

Background The present study aimed to prepare effective silk derived formulations in combination with plant extract (Aloe vera gel) to speed up the wound healing process in diabetic mice. Methods Diabetes was induced in albino mice by using alloxan monohydrate. After successful induction of diabetes in mice, excision wounds were created via biopsy puncture (6 mm). Wound healing effect of silk sericin (5%) and silk fibroin (5%) individually and in combination with 5% Aloe vera gel was evaluated by determining the percent wound contraction, healing time and histological analysis. Results The results indicated that the best biocompatible silk combination was of 5% silk fibroin and 5% Aloe vera gel in which wounds were healed in 13 days with wound contraction: 98.33 ± 0.80%. In contrast, the wound of the control group (polyfax) healed in 19 day shaving 98.5 ± 0.67% contraction. Histological analysis revealed that the wounds which were treated with silk formulations exhibited an increased growth of blood vessels, collagen fibers, and much reduced inflammation. Conclusion It can be concluded that a combination of Bombyx mori silk and Aloe vera gel is a natural biomaterial that can be utilized in wound dressings and to prepare more innovative silk based formulations for speedy recovery of chronic wounds.

scholarly journals Chitosan from Lucilia cuprina (Diptera: Calliphoridae) enhances sensitization to insulin treatment in a diabetic burn mice of wound healing

2020 ◽  
Vol 1 (1) ◽  
pp. 1-15
Author(s):  
Lamia M. El-Samad ◽  
◽  
Azza A. Attia ◽  
Basant A. Bakr ◽  
◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Lucilia Cuprina ◽  
Diabetic Mice ◽  
Burn Wound ◽  
Time Intervals ◽  
Burn Wound Healing ◽  
High Degree

Chitosan is recognized as a multipurpose biomaterial because of its low allergenicity, non-toxicity, biodegradability and biocompatibility. The present study was designed to estimate the role of chitosan derived from Lucilia cuprina on burn healing in diabetic mice; using histopathological and microbiological studies at different time intervals. Chitosan was prepared from L. cuprina with high molecular weight (MW) and high degree of deacetylation (DD) to evaluate its burn wound healing potential; skin burn closure assessment, histological and microbiological studies in vivo in male diabetic mice. Chitosan topical treatment was superior in wound closure acceleration; mainly in insulin injected group at all the time intervals. Additionally, earlier epidermal remodelling with mature and intense collagen deposition was encountered in all chitosan treated animals as well as non-diabetic burned animals. There was a significant delay in hair growth and poor epidermal remodelling with impairment of wound closure in diabetic groups. Moreover, chitosan treated groups assert the chitosan antibacterial effects with protecting the burn against contamination that hinders healing especially in this diabetic condition. Further researches needed to interpret effects of possible synergistic combination therapy.

scholarly journals Adenosine Diphosphate Improves Wound Healing in Diabetic Mice Through P2Y12 Receptor Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Paula Alvarenga Borges ◽  
Ingrid Waclawiak ◽  
Janaína Lima Georgii ◽  
Vanderlei da Silva Fraga-Junior ◽  
Janaína Figueiredo Barros ◽  
...  
Keyword(s):  
Wound Healing ◽  
T Cells ◽  
Receptor Antagonist ◽  
Tissue Repair ◽  
Cellular Response ◽  
Chronic Wounds ◽  
Γδ T Cells ◽  
Receptor Activation ◽  
Skin Wounds ◽  
Diabetic Mice

Chronic wounds are a public health problem worldwide, especially those related to diabetes. Besides being an enormous burden to patients, it challenges wound care professionals and causes a great financial cost to health system. Considering the absence of effective treatments for chronic wounds, our aim was to better understand the pathophysiology of tissue repair in diabetes in order to find alternative strategies to accelerate wound healing. Nucleotides have been described as extracellular signaling molecules in different inflammatory processes, including tissue repair. Adenosine-5’-diphosphate (ADP) plays important roles in vascular and cellular response and is immediately released after tissue injury, mainly from platelets. However, despite the well described effect on platelet aggregation during inflammation and injury, little is known about the role of ADP on the multiple steps of tissue repair, particularly in skin wounds. Therefore, we used the full-thickness excisional wound model to evaluate the effect of local ADP application in wounds of diabetic mice. ADP accelerated cutaneous wound healing, improved new tissue formation, and increased both collagen deposition and transforming growth factor-β (TGF-β) production in the wound. These effects were mediated by P2Y12 receptor activation since they were inhibited by Clopidogrel (Clop) treatment, a P2Y12 receptor antagonist. Furthermore, P2Y1 receptor antagonist also blocked ADP-induced wound closure until day 7, suggesting its involvement early in repair process. Interestingly, ADP treatment increased the expression of P2Y12 and P2Y1 receptors in the wound. In parallel, ADP reduced reactive oxygen species (ROS) formation and tumor necrosis factor-α (TNF-α) levels, while increased IL-13 levels in the skin. Also, ADP increased the counts of neutrophils, eosinophils, mast cells, and gamma delta (γδ) T cells (Vγ4+ and Vγ5+ cells subtypes of γδ+ T cells), although reduced regulatory T (Tregs) cells in the lesion. In accordance, ADP increased fibroblast proliferation and migration, myofibroblast differentiation, and keratinocyte proliferation. In conclusion, we provide strong evidence that ADP acts as a pro-resolution mediator in diabetes-associated skin wounds and is a promising intervention target for this worldwide problem.

scholarly journals Useful Effects of Melatonin in Peripheral Nerve Injury and Development of the Nervous System

2017 ◽  
Vol 12 (01) ◽  
pp. e1-e6 ◽  
Author(s):  
Yigit Uyanikgil ◽  
Turker Cavusoglu ◽  
Kubilay Kılıc ◽  
Gurkan Yigitturk ◽  
Servet Celik ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Nervous System ◽  
Peripheral Nerve ◽  
Peripheral Nerve Injury ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
High Efficacy ◽  
Nerve Injuries ◽  
Age Related

This review summarizes the role of melatonin (MLT) in defense against toxic-free radicals and its novel effects in the development of the nervous system, and the effect of endogenously produced and exogenously administered MLT in reducing the degree of tissue and nerve injuries. MLT was recently reported to be an effective free radical scavenger and antioxidant. Since endogenous MLT levels fall significantly in senility, these findings imply that the loss of this antioxidant could contribute to the incidence or severity of some age-related neurodegenerative diseases. Considering the high efficacy of MLT in overcoming much of the injury not only to the peripheral nerve but also to other organs, clinical trials for this purpose should be seriously considered.

scholarly journals Role of Chemokine Receptor CCR4 and Regulatory T Cells in Wound Healing of Diabetic Mice

2019 ◽  
Vol 139 (5) ◽  
pp. 1161-1170 ◽  
Author(s):  
Janaína F. Barros ◽  
Ingrid Waclawiak ◽  
Cyntia Pecli ◽  
Paula A. Borges ◽  
Janaína L. Georgii ◽  
...  
Keyword(s):  
Wound Healing ◽  
T Cells ◽  
Regulatory T Cells ◽  
Chemokine Receptor ◽  
Diabetic Mice ◽  
Chemokine Receptor Ccr4

scholarly journals Role of infection in wound healing

2020 ◽  
Vol 19 (4) ◽  
pp. 598-602
Author(s):  
Malik Asif Hussain ◽  
Flavia Huygens
Keyword(s):  
Wound Healing ◽  
Pathogenic Bacteria ◽  
Chronic Wounds ◽  
Medical Science ◽  
Vascular Diseases ◽  
Research Papers ◽  
Patients With Diabetes ◽  
Research Findings ◽  
The Impact

Chronic wounds, particularly infected wounds are clinically very important due to their significant impact on health budgets as well as patients` health worldwide. Patients with diabetes mellitus, vascular diseases especially peripheral vascular disease and pressure ulcers are major categories of patients presenting with chronic wounds. It is known that there are multiple factors determining chronic wound prognosis. The presence of multiple types of pathogenic bacteria, with specific virulence and adherent (biofilm) properties, contribute a significant role to the development of chronic wounds. This review article is based on the research project entitled” An investigation of the impact of bacterial diversity, pathogenic determinants and biofilms on chronic wounds”. The research findings have been published in form of research papers as well as conference posters. The aim of this article is to highlight various important aspects of bacterial impact on wound healing. Bangladesh Journal of Medical Science Vol.19(4) 2020 p.598-602

Protective Role of Melatonin and Coenzyme Q10 in Ochratoxin A Toxicity in Rat Liver and Kidney

2007 ◽  
Vol 26 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Emine Sutken ◽  
Erinc Aral ◽  
Filiz Ozdemir ◽  
Sema Uslu ◽  
Ozkan Alatas ◽  
...  
Keyword(s):  
Protective Effect ◽  
Ochratoxin A ◽  
Coenzyme Q ◽  
Kidney Tissue ◽  
Treated Group ◽  
Protective Role ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Liver And Kidney

Melatonin (MEL) and coenzyme Q10 (CoQ10) both display antioxidant and free radical scavenger properties. In the present study, the effect of MEL and CoQ10 on the oxidative stress and fibrosis induced by ochratoxin A (OTA) administration in rats was investigated. Rats were divided into five equal groups, each consisting of seven rats: (1) controls; (2) OTA-treated rats (289 μg/kg/day); (3) OTA+MEL–treated rats (289 μg/kg/day OTA + 10 mg/kg/day MEL); and (4) OTA+CoQ10–treated rats (289 μg/kg/day OTA +1 mg/100 g/day body weight (bw) CoQ10). After 4 weeks of treatment, the level of malondialdehyde (MDA), glutathione peroxidase (GPx), and hydroxyproline (Hyp) were measured in the homogenates of liver and kidney. In the OTA-treated group, the levels of MDA and Hyp in both liver and kidney were significantly increased when compared with the levels of control, whereas GPx activities decreased. In OTA+MEL–treated rats, the levels of MDA and Hyp in both liver and kidney were significantly decreased when compared with the levels of OTA-treated rats; however; GPX activities increased. In the OTA+CoQ10–treated group, the levels of MDA and Hyp were decreased when compared with the levels of OTA-treated rats, whereas GPx activities increased. In the OTA+CoQ 10–treated group, the levels of MDA, Hyp, and GPx were not significantly changed in kidney when compared with OTA-treated group. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and fibrosis both liver and kidney. Although CoQ10 has protective effect against OTA toxicity in liver tissue, it has no effect in kidney tissue.

scholarly journals Day and Night GSH and MDA Levels in Healthy Adults and Effects of Different Doses of Melatonin on These Parameters

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Shilpa Chakravarty ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Membrane Lipid ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Secretory Product ◽  
Therapeutic Implications ◽  
Antioxidative Function ◽  
Reliable Marker

The pineal secretory product melatonin (chemically, N-acetyl-5-methoxytryptamine) acts as an effective antioxidant and free-radical scavenger and plays an important role in several physiological functions such as sleep induction, immunomodulation, cardiovascular protection, thermoregulation, neuroprotection, tumor-suppression and oncostasis. Membrane lipid-peroxidation in terms of malondialdehyde (MDA) and intracellular glutathione (GSH) is considered to be a reliable marker of oxidative stress. The present work was undertaken to study the modulating effect of melatonin on MDA and GSH in human erythrocytes during day and night. Our observation shows the modulation of these two biomarkers by melatonin, and this may have important therapeutic implications.In vitrodose-dependent effect of melatonin also showed variation during day and night. We explain our observations on the basis of melatonin's antioxidative function and its effect on the fluidity of plasma membrane of red blood cells. Rhythmic modulation of MDA and GSH contents emphasized the role of melatonin as an antioxidant and its function against oxidative stress.

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