Brain is a Possible Target of Oxidative Damage in a Glaucoma Rat Model.

FERREIRA, S., ; REIDES, C, ; LERNER F, ; BRUNZINI R, ; LLESUY S

Congreso; ARVO; 2011

Purpose: To establish if the brain is a target of oxidative stress damage in an experimental glaucoma model. Methods: Ocular hypertension was induced in Wistar rats (n=12) cauterizing two episcleral veins under a surgical microscope (GG). A sham procedure (n=12) was performed in the control group (CG). In order to assess the occurrence of oxidative stress the following markers were evaluated in brain at seven days after surgery: the activities of antioxidant enzymes thioredoxin reductase (TR), glutathione peroxidase (GPX) and glutathione reductase (GR), the activities of glucose-6-phosphate dehydrogenase (G6PD) and NADPH oxidase (NAOX), spontaneous chemiluminescence associated with oxidative stress (CL), carbonyl groups (PC), nitrite concentration (NC), total antioxidant capacity (TRAP) and glutathione (GSH) levels. Results: TR activity was 0.19 ¡Ó 0.04 nmol/min.mg prot in GG (CG 0.42 ¡Ó 0.03 nmol/min.mg prot p< 0.05). GPX activity was 0.067 ¡Ó 0.008 U/min.mg prot in GG (CG 0.042 ¡Ó 0.003 U/min.mg prot p< 0.05). GR in GG was 6.0 ¡Ó 0.10 mmol/ min.mg prot (CG 10.2 ¡Ó 0.4 mmol/min.mg prot p< 0.05). G6PD was 0.03 ¡Ó 0.01 U/min.mg prot for GG (CG 0.15 ¡Ó 0.04 mmol/min.mg prot p< 0.05). The activity of NAOX was 0.114 ¡Ó 0.015 U/mg prot in GG (CG 0,046 ¡Ó 0.015 U/mg prot p< 0.01). CL in GG was 690 ¡Ó 41 cpm/mg prot (CG 432 ¡Ó 29 cpm/mg prot p< 0.001). PC was 2.84 ¡Ó 0.216 nmoles/mg prot in GG (CG 1.46 ¡Ó 0.27 nmoles/mg prot p< 0.001). NC was 5.30 ¡Ó 0.25 ƒÝM for GG (CG 4.41 ¡Ó 0.24 ƒÝM p< 0.05). TRAP was 50% decreased in GG (CG 153 ¡Ó 18 ƒÝM p< 0,001). GSH concentration was 1.98 ¡Ó 0.13 ƒÝmol/g organ for GG (CG 8.19 ¡Ó 0.71 ƒÝmol/g organ p< 0.001). Conclusions: Reactive oxygen and nitrogen species were increased in brain as evidenced by the increased in the activity of NAOX, chemiluminescence, protein carbonylation and nitrite concentration. The activities of enzymes associated with glutathione metabolism were decreased except for GPX suggesting an adaptative response to increased oxidative damage. The decrease in non-enzymatic antioxidants and a compensatory up-regulation of GPX activity may be a consequence of an increase in oxidative process. CR: None Support: University of Buenos Aires (Grant number: B024)