Anti-Apoptotic Effects of Dapsone After Spinal Cord Injury in Rats.
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.
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez S.S.A., Ave. Insurgentes Sur No. 3877, 14269, Mexico City, DF, Mexico.
Camilo
C
Ríos
Sandra
S
Orozco-Suarez
Hermelinda
H
Salgado-Ceballos
Marisela
M
Mendez-Armenta
Concepción
C
Nava-Ruiz
Iván
I
Santander
Veronica
V
Barón-Flores
Nadia
N
Caram-Salas
Araceli
A
Diaz-Ruiz
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D003622:Dapsone / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D005493:Folic Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*
D005493:Folic Acid Antagonists; D003622:Dapsone; D020169:Caspases