Neuroprotective effect of dapsone in an occlusive model of focal ischemia in rats

Rı́os, Camilo; Nader-Kawachi, Juan; Rodriguez-Payán, Ana Julia; Nava-Ruíz, Concepción

doi:10.1016/j.brainres.2003.11.040

Cited by 27 publications

(4 citation statements)

References 18 publications

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“…Recent research revealed that dapsone can influence functions of the central nerve system [86, 120, 129, 130, 160]. More precisely, it could be shown that dapsone suppresses experimentally induced neurotoxicity [138].…”

Section: Anti-inflammatory Mechanisms Of Actionmentioning

confidence: 99%

Dapsone in dermatology and beyond

2013

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Dapsone (4,4′-diaminodiphenylsulfone) is an aniline derivative belonging to the group of synthetic sulfones. In 1937 against the background of sulfonamide era the microbial activity of dapsone has been discovered. Shortly thereafter, the use of dapsone to treat non-pathogen-caused diseases revealed alternate antiinflammatory mechanisms that initially were elucidated by inflammatory animal models. Thus, dapsone clearly has dual functions of both: antimicrobial/antiprotozoal effects and anti-inflammatory features similarly to non-steroidal anti-inflammatory drugs. The latter capabilities primarily were used in treating chronic inflammatory disorders. Dapsone has been investigated predominantly by in vitro methods aiming to get more insights into the effect of dapsone to inflammatory effector cells, cytokines, and/or mediators, such as cellular toxic oxygen metabolism, myoloperoxidase-/halogenid system, adhesion molecules, chemotaxis, membrane-associated phospholipids, prostaglandins, leukotrienes, interleukin-8, tumor necrosis factor α, lymphocyte functions, and tumor growth. Moreover, attention has been paid to mechanisms by which dapsone mediates effects in more complex settings like impact of lifespan, stroke, glioblastoma, or as anticonvulsive agent. Additionally, there are some dermatological investigations in human being using dapsone and its metabolites (e.g., leukotriene B4-induced chemotaxis, ultraviolet-induced erythema). It could be established that dapsone metabolites by their own have anti-inflammatory properties. Pharmacology and mechanisms of action are determining factors for clinical use of dapsone chiefly in neutrophilic and/or eosinophilic dermatoses and in chronic disorders outside the field of dermatology. The steroid-sparing effect of dapsone is useful for numerous clinical entities. Future avenues of investigations will provide more information on this fascinating and essential agent.

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Section: Anti-inflammatory Mechanisms Of Actionmentioning

confidence: 99%

Dapsone in dermatology and beyond

2013

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“…Dapsone, also known as 4,4′-diamino-diphenylsulfone, is a neuroprotective compound that acts by suppressing glutamate-mediated excitotoxicity and possesses anti-inflammatory properties [ 87 , 88 ]. The anti-inflammatory properties of dapsone are attributed to its ability to hinder the calcium-dependent actions of neutrophils, which includes the suppression of harmful oxidants and proteases released by these cells, leading to tissue damage.…”

Section: Discussionmentioning

confidence: 99%

“…The anti-inflammatory properties of dapsone are attributed to its ability to hinder the calcium-dependent actions of neutrophils, which includes the suppression of harmful oxidants and proteases released by these cells, leading to tissue damage. Furthermore, dapsone irreversibly inhibits myeloperoxidase, blocks peroxidase functioning in eosinophils, inhibits the synthesis of products by 5-lipoxygenase products, and decreases the levels of neurotoxic free radicals [ 87 , 88 , 89 , 90 ]. A prospective randomized and double-blind trial investigating dapsone in acute ischemic stroke revealed that patients receiving dapsone had significant improved neurological functioning at 2 months after acute ischemic stroke compared to the placebo group [ 90 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Drug Therapy in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Prospective Randomized and Placebo-Controlled Trials

Wach

Vychopen

Güresir

et al. 2023

JCM

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Emerging evidence suggests that neuroinflammation may play a potential role in aneurysmal subarachnoid hemorrhage (aSAH). We aim to analyze the influence of anti-inflammatory therapy on survival and outcome in aSAH. Eligible randomized placebo-controlled prospective trials (RCTs) were searched in PubMed until March 2023. After screening the available studies for inclusion and exclusion criteria, we strictly extracted the main outcome measures. Dichotomous data were determined and extracted by odds ratio (OR) with 95% confidence intervals (CIs). Neurological outcome was graded using the modified Rankin Scale (mRS). We created funnel plots to analyze publication bias. From 967 articles identified during the initial screening, we included 14 RCTs in our meta-analysis. Our results illustrate that anti-inflammatory therapy yields an equivalent probability of survival compared to placebo or conventional management (OR: 0.81, 95% CI: 0.55–1.19, p = 0.28). Generally, anti-inflammatory therapy trended to be associated with a better neurologic outcome (mRS ≤ 2) compared to placebo or conventional treatment (OR: 1.48, 95% CI: 0.95–2.32, p = 0.08). Our meta-analysis showed no increased mortality form anti-inflammatory therapy. Anti-inflammatory therapy in aSAH patients tends to improve the neurological outcome. However, multicenter, rigorous, designed, prospective randomized studies are still needed to investigate the effect of fighting inflammation in improving neurological functioning after aSAH.

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“…Dapsone has been safe and beneficial in animal studies [75] and a clinical pilot study with 30 patients [76]. A phase III trial using a dose of 250 mg (intravenously) administered within 12 h after onset is still in progress [77].…”

Section: Therapeutic Management Of Strokementioning

confidence: 99%

Drug Therapy in Stroke: From Preclinical to Clinical Studies

Kaur¹,

Prakash²,

Medhi³

2013

Pharmacology

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Background: Stroke is one of the major challenges to health and the reason for increasing disability-adjusted life years. Despite tremendous progress in preclinical studies, none of the treatment options has proven efficacious in clinical studies. The basic aim of neuroprotection is to interfere with the events of the ischemic cascade, halt the pathological processes and prevent the death of vulnerable nerve cells in the ischemic penumbra. Summary: This review will provide a brief overview of the current understanding of stroke, including the global epidemiology of stroke, its pathophysiology, the targeting of specific pathways and the success and failure of preclinical as well as clinical studies, and it will discuss the emerging targets for novel therapeutic strategies under investigation. Key Messages: New advancing investigational drugs for the prevention and treatment of stroke are on the way and may someday give hope to neuroscientists and clinicians. A novel approach should adopt preclinical testing, advance the understanding of the pathophysiology of stroke and make it possible to translate it from bench to bedside. We should learn from the past failures and move on with more enthusiasm.

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Neuroprotective effect of dapsone in an occlusive model of focal ischemia in rats

Cited by 27 publications

References 18 publications

Dapsone in dermatology and beyond

Dapsone in dermatology and beyond

Anti-Inflammatory Drug Therapy in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Prospective Randomized and Placebo-Controlled Trials

Drug Therapy in Stroke: From Preclinical to Clinical Studies

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