Sodium Valproate Improves Skin Flap Survival via Gamma-Aminobutyric Acid and Histone Deacetylase Inhibitory System

Ala, Moein; Jafari, Razieh Mohammad; Nematian, Hossein; Ganjedanesh, Mohammad Reza; Dehpour, Ahmad Reza

doi:10.1016/j.jss.2019.09.036

Cited by 14 publications

(13 citation statements)

References 41 publications

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“…Contrary to the findings of the consulted authors [5][6][7][8] , who reported an increase in collagen types I and III, when immunohistochemical staining was used, there was less collagen I in the sections obtained from the treated animals and more type III collagen. This finding supports the hypothesis that the healing process of the animals treated with VPA was less evolved than in the control group.…”

Section: Discussioncontrasting

confidence: 93%

“…Darby and Hewitson 7 observed that the levels of α-SMA, which identifies contractile proteins and therefore myofibroblasts, as well as markers for collagen I and collagen III were increased in wounds treated with VPA. Ala et al 8 used valproate at different dosages, in rats, intraperitoneally, and reported that skin flaps healed faster in the VPA group.…”

Section: Introductionmentioning

confidence: 99%

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The effects of valproic acid on skin healing: experimental study in rats

Biondo-Simões

Ioshii

et al. 2022

Acta Cir. Bras.

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To recognize the effects of valproic acid (VPA), an epigenetic drug, on the skin healing process. Methods: Sixty male Wistar rats were divided into two groups: the experiment treated with VPA (100 mg/kg/day); and the control, with 0.9% sodium chloride by gavage. Skin healing was studied in three moments (the third, the seventh, and the 14th day), evaluating the parameters: inflammatory reaction and its intensity (anti-LCA), angiogenesis (anti-CD34), collagen I and III (anti-collagen I, anti-collagen III and Picrosirius-red F3BA) and myofibroblasts (anti-alpha-AMS). Results: The inflammatory reaction was acute or sub-acute in both groups on the third day. On the seventh and the 14th day, chronic predominated in the control (p=0.006), and sub-acute in the experiment (p=0.020). There was a greater number of leukocytes in the group treated only on the third day (p=0.036). The number of vessels was lower in the treated group at the three times (p3=0.002, p7<0.001, and p14=0.027). Myofibroblasts were rare in the third day and moderate quantity in the remaining periods. Collagen I density was higher in the control at the three times (p<0.001) and collagen III in the treated group (p<0.001). Conclusion: VPA led to a more intense inflammatory reaction, decreased angiogenesis and collagen deposition, especially type I collagen.

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Section: Discussioncontrasting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

The effects of valproic acid on skin healing: experimental study in rats

Biondo-Simões

Ioshii

et al. 2022

Acta Cir. Bras.

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“…Sodium valproate improves secondary wound healing, thought to be due to a GABA and HDAC‐mediated up‐regulation of TGF‐β and various growth factors, 97 an effect which is potentiated further when co‐administered with TSA 97 . Furthermore, phenylbutyrate (a short‐chain fatty acid HDAC inhibitor) promotes epithelial healing following radiation injury 98 .…”

Section: Micrornasmentioning

confidence: 99%

A review of epigenetic regulation in wound healing: Implications for the future of wound care

Lewis

Stevenson

Fear

et al. 2020

Wound Repair Regeneration

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Epigenetic regulatory mechanisms are essential for maintaining skin homeostasis and aid in the processes of wound healing. The nucleus co‐ordinates gene expression using epigenetic regulatory mechanisms based on distinct chromatin structural states and their remodeling. These include DNA methylation and hydroxymethylation, post‐translational histone modifications, ATP‐dependent chromatin remodeling and higher‐order chromatin structure and 3D genome organization. Epigenetic pathways play a key role in co‐ordinating the behavior and activity of the multitude of cell types seen during skin repair, and research is now focusing on how wound healing can be modulated by altering the activity of certain reparative genes. Herein, we aim to highlight recent advances in understanding epigenetic regulatory mechanisms, with particular reference to those involved in keratinocyte and fibroblast biology. We also propose future directions for exploration of epigenetic mechanisms, and their potential clinical applications in acute wound care.

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“…[9] Valproate may modify neurogenic meningitis through a GABA-dependent mechanism. [10] In the treatment of schizophrenia borderline personality disorder and acquired brain injury, this drug is used off-label. [8,11] No single mechanism of action for sodium valproate fully accounts for its various clinical indications and broad spectrum of efficacy.…”

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confidence: 99%

“…[1] It has effects on dopamine, enhances gammaaminobutyric acid (GABA) receptors through activation of gamma-aminobutyric acid (GABA)-sensitive chloride channels and inhibition of histone deacetylase, and inhibits NMDA-induced neuroexcitatory signals. [7,8,10] The main component of sodium valproate is valproic acid (VPA), which is a branched short-chain fatty acid. [12] Regardless of which oral form of sodium valproate is taken, it is rapidly absorbed, and peak serum concentrations are reached within 1 to 3 h. [4] All oral forms are highly bioavailable and extended-release formulations are excellent to minimize fluctuations in serum drug concentration.…”

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confidence: 99%

What are the effects of taking 300 pills of sodium valproate? - case report

Pożarowska

Brzuszkiewicz

Rudziński

et al. 2022

J Educ Health Sport

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INTRODUCTION: Sodium valproate is one of the most important antiepileptic drugs. It can be effective as a preventive treatment for migraine, it has also found use in the maintenance treatment of bipolar disorder and acute mania,it is sometimes used in the treatment of chronic neuropathic pain and fibromyalgia, in the treatment of schizophrenia borderline personality disorder and acquired brain injury, this drug is used off-label. Its overdose can be fatal. MATERIALS AND METHOD: Patient information was collected from hospital records available in the clinical toxicology department. In addition, we conducted a literature review on sodium valproate treatment, its toxicity, side effects and pharmacokinetics using PubMed. CASE REPORT: A 57-year-old patient with a history of depressive disorders was admitted to the Clinical Department of Toxicology and Cardiology in Lublin for intentional intoxication with the drug Absenor (sodium valproate). The patient had taken 3 packages of Absenor 500 mg (300 tablets in total) for suicidal purposes. The determined concentration of valproic acid was 841 µg/ml, and the patient's condition was very severe. Despite the treatment administered-multiple attempts at gastric lavage, administration of activated charcoal, performance of hemodialysis procedures, administration of infusion of catecholamines, the patient died on the fifth day of hospitalization. CONCLUSION: An overdose of sodium valproate can be fatal. Keep this in mind when ordering this drug for patients with a positive history of suicide attempts.

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Sodium Valproate Improves Skin Flap Survival via Gamma-Aminobutyric Acid and Histone Deacetylase Inhibitory System

Cited by 14 publications

References 41 publications

The effects of valproic acid on skin healing: experimental study in rats

The effects of valproic acid on skin healing: experimental study in rats

A review of epigenetic regulation in wound healing: Implications for the future of wound care

What are the effects of taking 300 pills of sodium valproate? - case report

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