Reduction of ischemic brain damage and increase of glutathione by a liposomal preparation of quercetin in permanent focal ischemia in rats.
Oxidative stress is implicated in the pathogenesis of cerebral ischemia injury, and the flavonoids have shown to be neuroprotective in experimental models of cerebral ischemia. Previously, we have shown that an aqueous preparation of quercetin did not reach the brain while a liposomal preparation produced measurable cerebral amounts of quercetin that reduced significantly the cerebral damage provoked by permanent middle cerebral artery occlusion (pMCAo) of rats. In this context, the protective effects of liposomal quercetin (LQ) were investigated in the same model after 1 and 4 hours of arterial occlusion. LQ was administered in a single dose (30 mg/kg), at 30 min, 1 and 4 h after pMCAo, and the brain was studied 24 h later. Cerebral damage and the oedema volume were assessed with a tetrazolium salt (TTC). The status of brain tissue, the neuronal population, the global motor behaviour as well as the antioxidant, endogenous reduced glutathione (GSH), were also assessed in the brain. Thirty min after LQ there was a significantly protective effect against ischemic lesion demonstrated by a significant increase in numbers of cells in striatum and cortex, together with a partial reversal of motor deficits. GSH levels decreased after ischemia in ipsilateral striatum and cortex, and the LQ preparation reversed these effects 24 h after the occlusion. Our results suggest that endogenous brain GSH is critical in the defense mechanisms after ischemia, as a significant mediator of the protective effects of the LQ preparation.
Rivera
Felicia
F
Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. frivera@iibce.edu.uy
Costa
Gustavo
G
Abin
Andrés
A
Urbanavicius
Jessika
J
Arruti
Cristina
C
Casanova
Gabriela
G
Dajas
Federico
F
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008081:Liposomes / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009562:Nissl Bodies; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling
D000975:Antioxidants; D008081:Liposomes; D018696:Neuroprotective Agents; D011794:Quercetin; D005978:Glutathione