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 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.
Diaz-Ruiz
Araceli
A
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez S.S.A., D.F. México, México.
Zavala
Carlos
C
Montes
Sergio
S
Ortiz-Plata
Alma
A
Salgado-Ceballos
Hermelinda
H
Orozco-Suarez
Sandra
S
Nava-Ruiz
Concepción
C
Pérez-Neri
Iván
I
Perez-Severiano
Francisca
F
Ríos
Camilo
C
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D053148:Caspase 3 / Q000187:drug effects; D053453:Caspase 9 / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003622:Dapsone / Q000494:pharmacology*; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009195:Peroxidase / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; C002744:3-nitrotyrosine; D014443:Tyrosine; D003622:Dapsone; D009195:Peroxidase; D053148:Caspase 3; D053453:Caspase 9