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Review
. 2022;20(1):194-210.
doi: 10.2174/1570159X19666210617143108.

Dapsone, More than an Effective Neuro and Cytoprotective Drug

Araceli Diaz-Ruiz  1 , Juan Nader-Kawachi  2 , Francisco Calderón-Estrella  3 , Alfonso Mata-Bermudez  4 , Laura Alvarez-Mejia  1 , Camilo Ríos  5
Affiliations
Review

Dapsone, More than an Effective Neuro and Cytoprotective Drug

Araceli Diaz-Ruiz et al. Curr Neuropharmacol. 2022.

Abstract

Dapsone (4,4'-diamino-diphenyl sulfone) is a synthetic derivative of sulfones, with the antimicrobial activity described since 1937. It is also a drug traditionally used in dermatological therapies due to its anti-inflammatory effect. In recent years its antioxidant, antiexcitotoxic, and antiapoptotic effects have been described in different ischemic damage models, traumatic damage, and models of neurodegenerative diseases, such as Parkinson's (PD) and Alzheimer's diseases (AD). Finally, dapsone has proven to be a safe and effective drug as a protector against heart, renal and pulmonary cells damage; that is why it is now employed in clinical trials with patients as a neuroprotective therapy by regulating the main mechanisms of damage that lead to cell death ObjectiveThe objective of this study is to provide a descriptive review of the evidence demonstrating the safety and therapeutic benefit of dapsone treatment, evaluated in animal studies and various human clinical trials Methods: We conducted a review of PubMed databases looking for scientific research in animals and humans, oriented to demonstrate the effect of dapsone on regulating and reducing the main mechanisms of damage that lead to cell death ConclusionThe evidence presented in this review shows that dapsone is a safe and effective neuro and cytoprotective treatment that should be considered for translational therapy.

Keywords: Dapsone; anti-inflammatory; antiapoptotic; antiexcitotoxic; antioxidant; cytoprotection; neuroprotection.

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Figures

Fig. (1)
Fig. (1)
Dapsone chemical structure.
Fig. (2)
Fig. (2)
Neuroprotective and cytoprotective mechanisms of dapsone. 1) Antiexcitotoxic effect: Regulates glutamate release preventing the activation of metabotropic and ionotropic receptors (m-GluR y NMDA, respectively) as well as Glu receptors (AMPARs) and kainate receptors (KA), which leads to avoid membrane depolarization inhibiting the opening of voltage-gated calcium channels (VGCCs), voltage-dependent sodium channels (VGSC) and voltage gated-potassium channels (VGKC), regulating the signaling cascade and ions liberation. 2. Antioxidant effect: Decrease the formation of superoxide radical (O2-) and hydrogen peroxide (H2O2), produced in mitochondria during the excitotoxic and ischemic process, avoiding cell death and decrease the NO production and peroxynitrite (ONOO-). 3) Dapsone regulates formation of the multiprotein complex known as inflammasome active by Toll-like receptor 4 (TLR4) attenuating the assembly of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) interacting with the ASC and recruits the Caspase-1 (Cas-1) responsible of formation of proinflammatory interleukins (IL-1β y IL-18). 4) Antiinflamatory effect: regulates metabolism of arachidonic acid mediated by cyclooxygenase (COX) and lipoxygenase (LOX) through inhibition of phospholipase A2, reducing the formation of chemoattractants as prostaglandins (PGDs), thromboxanes (TXBs) and leukotrienes (LTs). 5) Antiapoptotic effect: Regulates both the intrinsic as extrinsic way of apoptosis mediated by the activation of several caspases.
Fig. (3)
Fig. (3)
Anti-inflammatory effect of dapsone in several diseases. Alzheimer’s disease and dementia syndrome the evidence shows that dapsone decreased levels of IL-8. Multiple sclerosis, it is proposed that due to the histopathological characteristics of the disease, dapsone treatment may decrease the levels of various pro-inflammatory cytokines (IL-1β, IL-18 and IL-8) and the expression of the transcription factor NFkB. Respiratory disease model a decrease in IL8 and expression of the transcription NFκB factor were observed. Acute respiratory distress syndrome (ARDS), Middle East respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19), by pathophysiological characteristics the dapsone may be decrease the levels of various proinflammatory cytokines (IL-1β, IL-6, IL-8 and TNFα). Acnes showed diminished of IL-1β, IL-6, IL-8 and NFκB factor. Heart damage TNFα and Creatine kinase-myocardial (CK-MB) diminished levels. Testicular damage (TNFα diminished level). Kidney ischemia damage (TNFα, IL-1β and Myeloperoxidase (MPO) decreased levels). Diabetes (IL-1β, IL-8, IL-18 and TNFα diminished levels). Brain ischemia and Spinal cord injury MPO decreased level. Tumors IL-8 decreased level. Blood vessels the dapsone lowers the levels of IL-8, IL-6 and TNFα by blocking the inflammatory response mediated by macrophages and neutrophils present in the blood vessels, an effect that may prevent the formation of extracellular neutrophil networks (NETs) traps and the disseminated thrombosis characteristic of the COVID-19 disease.
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