Dapsone attenuates kainic acid-induced seizures in rats

Altagracia, M; Monroy-Noyola, Antonio; Osorio-Rico, Laura; Kravzov, J; Alvarado-Calvillo, Raúl; Manjarrez-Marmolejo, Joaquín; Rı́os, Camilo

doi:10.1016/0304-3940(94)90869-9

Cited by 19 publications

(8 citation statements)

References 12 publications

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“…Interestingly, this therapeutic effect was observed only when the drugs were administered within a very short period (10 min) after injury. These results suggest that dapsone may be acting mainly through a mechanism independent of the antiexcitotoxic properties of the sulfone reported by our group (Altagracia et al, 1994;Santamaria et al, 1997;Rodriguez et al, 1999). Recently, we demonstrated the antioxidant, antiinflammatory, and antiapoptotic effects of dapsone in a rat model of brain ischemia and reperfusion (Diaz-Ruiz et al, 2008).…”

Section: Discussionmentioning

confidence: 57%

Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury

et al. 2011

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After spinal cord injury (SCI), a complex cascade of pathophysiological processes increases the primary damage. The inflammatory response plays a key role in this pathology. Recent evidence suggests that myeloperoxidase (MPO), an enzyme produced and released by neutrophils, is of special importance in spreading tissue damage. Dapsone (4,4'-diaminodiphenylsulfone) is an irreversible inhibitor of MPO. Recently, we demonstrated, in a model of brain ischemia/reperfusion, that dapsone has antioxidant, antiinflammatory, and antiapoptotic effects. The effects of dapsone on MPO activity, lipid peroxidation (LP) processes, motor function recovery, and the amount of spared tissue were evaluated in a rat model of SCI. MPO activity had increased 24.5-fold 24 hr after SCI vs. the sham group, and it had diminished by 38% and 19% in the groups treated with dapsone at 3 and 5 hr after SCI, respectively. SCI increased LP by 45%, and this increase was blocked by dapsone. In rats treated with dapsone, a significant motor function recovery (Basso-Beattie-Bresnahan score, BBB) was observed beginning during the first week of evaluation and continuing until the end of the study. Spontaneous recovery 8 weeks after SCI was 9.2 ± 1.12, whereas, in the dapsone-treated groups, it reached 13.6 ± 1.04 and 12.9 ± 1.17. Spared tissue increased by 42% and 33% in the dapsone-treated groups (3 and 5 hr after SCI, respectively) vs. SCI without treatment. Dapsone significantly prevented mortality. The results show that inhibition of MPO by dapsone significantly protected the spinal cord from tissue damage and enhanced motor recovery after SCI.

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Section: Discussionmentioning

confidence: 57%

Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury

et al. 2011

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“…The anti-apoptotic effects of dapsone may be due to its ability to regulate upstream the key mechanisms of injury leading to cell death (excitotoxic damage, oxidative stress, and exacerbated inflammatory response) [10,13,14,25,41,42].…”

Section: Discussionmentioning

confidence: 99%

Anti-Apoptotic Effects of Dapsone After Spinal Cord Injury in Rats

et al. 2015

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Spinal cord injury (SCI) is a condition producing irreversible damage to the neurological function. Among the leading mechanisms associated to cell death after SCI, excitotoxicity, oxidative stress, inflammatory response and apoptosis are considered potential targets to prevent tissue damage. We recently reported that dapsone an anti-inflammatory drug, decreases the activity of myeloperoxidase, lipid peroxidation, improve neurological function and increase the amount of spared tissue after SCI in rats. In this study, we characterized the anti-apoptotic effect of dapsone administered at 12.5 mg/kg/24 h dose, starting at 3 and 5 h after SCI. We monitored the activity of caspases-8, 9, and 3 and quantitated Annexin V and TUNEL positive cells in the core of the lesion. Results showed increased activities of caspase-8, 9 and 3 at 72 h by SCI to reach increments of 69, 143 and 293 %, respectively, as compared to sham group. Meanwhile, dapsone, administered at 3 and 5 after SCI, reduced caspase-8 activity by 36 and 44 % respectively, whereas the activity of caspase-9 was diminished by 37 %. Likewise, the activity of caspase-3 showed a decrease of 38 %. Finally, both Annexin V and TUNEL-positive cells were significantly reduced by DDS as compared to untreated SCI animals. Results showed that dapsone exerted anti-apoptotic effect after SCI.

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“…Again, this neuroprotective effect of dapsone was attributed to its antioxidative capacities. Anticonvulsive effects of dapsone have been described in earlier studies [4, 70, 78]. In the context of neurologic diseases, Japanese authors have reported successful therapy of steroid-dependent neuro-Sweet-disease that responded to 75 mg dapsone/day [141] (see 4.10).…”

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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Dapsone attenuates kainic acid-induced seizures in rats

Cited by 19 publications

References 12 publications

Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury

Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury

Anti-Apoptotic Effects of Dapsone After Spinal Cord Injury in Rats

Dapsone in dermatology and beyond

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