Antioxidant, antiinflammatory and antiapoptotic effects of dapsone in a model of brain ischemia/reperfusion in rats

Although dapsone (4,4′‐diaminodiphenylsulfone) has been described as a neuroprotective agent in occlusive focal ischemia in rats, its mechanism of action is still unknown. To explore this mechanism, oxidative, inflammatory and apoptotic processes were evaluated in the striatum of adult rats using a...

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Published in:Journal of neuroscience research 2008-11, Vol.86 (15), p.3410-3419
Main Authors: Diaz-Ruiz, Araceli, Zavala, Carlos, Montes, Sergio, Ortiz-Plata, Alma, Salgado-Ceballos, Hermelinda, Orozco-Suarez, Sandra, Nava-Ruiz, Concepción, Pérez-Neri, Iván, Perez-Severiano, Francisca, Ríos, Camilo
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - pharmacology
Antioxidants - pharmacology
apoptosis
Apoptosis - drug effects
Brain Ischemia - drug therapy
Caspase 3 - drug effects
Caspase 9 - drug effects
Chromatography, High Pressure Liquid
dapsone
Dapsone - pharmacology
Immunoblotting
In Situ Nick-End Labeling
ischemia/reperfusion
lipid peroxidation
Lipid Peroxidation - drug effects
Male
myeloperoxidase
Neuroprotective Agents - pharmacology
nitrotyrosine
Peroxidase - drug effects
Rats
Rats, Wistar
Reperfusion Injury - drug therapy
Tyrosine - analogs & derivatives
Tyrosine - drug effects
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Summary:Although dapsone (4,4′‐diaminodiphenylsulfone) has been described as a neuroprotective agent in occlusive focal ischemia in rats, its mechanism of action is still unknown. To explore this mechanism, oxidative, inflammatory and apoptotic processes were evaluated in the striatum of adult rats using a model of ischemia‐reperfusion (I/R), either with or without dapsone treatment. Male Wistar rats were submitted to transient middle cerebral artery occlusion for 2 hr, followed by reperfusion. Rats were dosed either with dapsone (12.5 mg/kg i.p.) or vehicle 30 min before or 30 min after the ischemia onset. Lipid peroxidation (LP) and nitrotyrosine contents were measured 22 hr after reperfusion, and myeloperoxidase activity was evaluated 46 hr after I/R. Different markers for apoptosis and necrosis were also evaluated both at 24 and 72 hr after I/R experimental procedure. LP increased by 37% in ischemic animals vs controls, and this effect was reversed by dapsone treatments. A similar effect was observed regarding nitrotyrosine striatal contents. Myeloperoxidase activity, a marker of inflammatory response, increased 3.7‐fold in ischemic animals vs. control rats, and dapsone treatment antagonized that effect. Although apoptosis was increased by the effect of ischemia at both evaluation times, dapsone antagonized that effect only at 72 hr after surgery. Dapsone antagonized all of the I/R end points measured, showing a remarkable ability to decrease markers of damage through antioxidant, antiinflammatory, and anti‐apoptotic effects. © 2008 Wiley‐Liss, Inc.
ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.21775